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To achieve sustainable shark fisheries, it is key to understand not only the biological drivers and environmental consequences of overfishing, but also the social and economic drivers of fisher behavior. The extinction risk of sharks is highest in coastal tropical waters, where small‐scale fisheries are most prevalent. Small‐scale fisheries provide a critical source of economic and nutritional security to coastal communities, and these fishers are among the most vulnerable social and economic groups. We used Kenya's and Zanzibar's small‐scale shark fisheries, which are illustrative of the many data‐poor, small‐scale shark fisheries worldwide, as case studies to explore the relationship between extinction risk and the economic and nutritional value of sharks. To achieve this, we combined existing data on shark landings, extinction risk, and nutritional value with sales data at 16 key landing sites and information from interviews with 476 fishers. Shark fisheries were an important source of economic and nutritional security, valued at >US$4 million annually and providing enough nutrition for tens of thousands of people. Economically and nutritionally, catches were dominated by threatened species (72.7% and 64.6–89.7%, respectively). The most economically valuable species were large and slow to reproduce (e.g. mobulid rays, wedgefish, and bull, silky, and mako sharks) and therefore more likely to be threatened with extinction. Given the financial incentive and intensive fishing pressure, small‐scale fisheries are undoubtedly major contributors to the decline of threatened coastal shark species. In the absence of effective fisheries management and enforcement, we argue that within small‐scale fisheries the conditions exist for an economically incentivized feedback loop in which vulnerable fishers are driven to persistently overfish vulnerable and declining shark species. To protect these species from extinction, this feedback loop must be broken. [ABSTRACT FROM AUTHOR]

Marine megafauna are critical for marine ecosystem health and their removal can cause food webs to collapse. Methods to reduce marine megafauna mortality can result in conflict between scientists, conservationists, fishers and fisheries management due to real or perceived effects on target catch, income and food security. Sensory deterrents have been used in attempts to mitigate bycatch and retain target catch quantity and quality. Here, we completed a systematic review of 116 papers, plus 25 literature reviews published between 1991 and 2022, to investigate potential for sensory deterrents to mitigate bycatch across four marine megafauna taxonomic groups (marine mammals, sea turtles, seabirds and elasmobranchs). Lights on gillnets are the only technology so far to result in significant bycatch reductions across all four taxonomic groups. It is difficult to make generalisations about the efficacy of sensory deterrents and their ability to deliver consistent bycatch reductions. The efficacy of each method is context dependent, varying with species, fishery and environmental characteristics. Further research is recommended for field studies assessing bycatch mitigation in all sensory deterrents, including combinations of deterrents, to assess effects on target and non-target species. The associated issues of habituation, habitat exclusion and foraging around fishing gear are important, although reducing mortality of vulnerable species should remain the highest priority for conservation and preserving ecosystems that fishers depend on. Multiple complementary measures will be required to achieve consistent bycatch reduction targets in many fisheries, of which sensory deterrents could play some part if implemented appropriately. [ABSTRACT FROM AUTHOR]

Nearshore coastal waters off Northumberland, UK, are important habitats for marine megafauna including marine mammals and seabirds. The area also features extensive anthropogenic activities including shipping, marine renewables development, fisheries, and tourism. Meanwhile there is lack of baseline data on odontocete occurrence to allow assessment of the potential impact from human disturbance. A recent increase in the number of sightings of common bottlenose dolphins (Tursiops truncatus) in the area has provided impetus for new data to inform conservation managers and policy makers. To provide this information, acoustic data were collected using broadband passive acoustic recorders at three sites (Druridge Bay, Newbiggin-by-the-Sea, and St Mary's Island) off the Northumberland coast and analyzed to identify species-specific click trains of common bottlenose dolphin, white-beaked dolphin (Lagenorhynchus albirostris) and harbor porpoise (Phocoena phocoena). Detection data were modelled for each species as detection-positive hours (DPH) using Generalized Additive Models with Generalized Estimating Equations (GAM-GEE) to investigate the effects of environmental covariates, including day of year, diel phase, lunar phase, salinity, year, month and sea surface temperature, and their interaction with location. A total of 20,845 h were recorded during the study resulting in a total of 1660, 71, and 1111 DPH identified for bottlenose dolphin, white-beaked dolphin and porpoise, respectively. The final model for bottlenose dolphins retained all covariates except tidal index and an interaction between location and day of year after model selection and all covariates in the final model were significant. The final model for white-beaked dolphin retained month, year, location, diel index, temperature, lunar index and interactions between location and diel index and all covariates except lunar index were significant. The final model for porpoise retained all covariates and interactions between location and diel phase, day of year, lunar index, and salinity, however, salinity and the interaction between location and lunar index were not significant. Bottlenose dolphin clicks were detected in the area year-round but with two peak periods in occurrence coinciding with May and late September; white-beaked dolphin clicks were detected predominantly in July and August; and porpoise clicks were present year-round but with much greater probability of detection at the Druridge Bay site, where there were peaks in winter and in September. The results of this study provide important information for conservation and management actions that may be needed to reduce anthropogenic pressures on odontocetes in UK waters. • A semi-supervised analysis pipeline was used to identify odontocete clicks to species level. • Environmental factors drive occurrence patterns of all identified species. • Seasonal patterns evident for each species; some suggestion of temporal segregation. • Year-round occurrence evident for common bottlenose dolphin. • Differences at small spatial scales identified for harbour porpoise. [ABSTRACT FROM AUTHOR]

Diabetes develops due to deficient functional β cell mass, insulin resistance, or both. Yet, various challenges in understanding the mechanisms underlying diabetes development in vivo remain to be overcome owing to the lack of appropriate intravital imaging technologies. To meet these challenges, we have exploited the anterior chamber of the eye (ACE) as a novel imaging site to understand diabetes basics and clinics in vivo. We have developed a technology platform transplanting pancreatic islets into the ACE where they later on can be imaged non-invasively for long time. It turns out that the ACE serves as an optimal imaging site and provides implanted islets with an oxygen-rich milieu and an immune-privileged niche where they undergo optimal engraftment, rich vascularization and dense innervation, preserve organotypic features and live with satisfactory viability and functionality. The ACE technology has led to a series of significant observations. It enables in vivo microscopy of islet cytoarchitecture, function and viability in the physiological context and intravital imaging of a variety of pathological events such as autoimmune insulitis, defects in β cell function and mass and insulin resistance during diabetes development in a real-time manner. Furthermore, application of the ACE technology in humanized mice and non-human primates verifies translational and clinical values of the technology. In this article, we describe the ACE technology in detail, review accumulated knowledge gained by means of the ACE technology and delineate prospective avenues for the ACE technology. [ABSTRACT FROM AUTHOR]

There are concerns about the short- and long-term effects on cetaceans from offshore construction using pile-driving. Gravity-base foundations and anchored floating turbines are alternative installation methods that may have less impact on cetaceans. In this study, we investigated the response of dolphins (Tursiops truncatus and Lagenorhynchus albirostris) and harbour porpoise (Phocoena phocoena) to the construction of wind turbines using gravity-base foundations off Blyth, Northumberland, United Kingdom using cetacean echolocation recorders (C-PODs). Data were collected at nine sites across 3 years (2016–2018) before, during and after construction. Generalised additive mixed models were used to investigate temporal, environmental, and anthropogenic drivers of dolphin and porpoise occurrence from 143,215 h (5967 days) of C-POD data. The models explained 27% and 30% of the deviance in dolphin and porpoise occurrence, respectively. Overall, the results showed no long-term effect on the dolphin occurrence from the construction of the gravity-base wind turbine array. In contrast, porpoise occurrence increased by 32% and 75%, respectively, in the years during and after construction, compared to the before-construction year. Other predictors of dolphin and porpoise occurrence included month, hour of day, tidal currents and vessel sonar activity. Our findings indicate that wind turbine installation using gravity-base foundations had no long-term effects on the occurrence of dolphins or porpoise and may represent an offshore construction methodology that is less impactful to dolphins and harbour porpoise than impact pile-driven turbine installation methods. These results are important for future offshore energy developments; however, further studies are recommended to investigate potential species and location variations. [ABSTRACT FROM AUTHOR]

Objectives Hyperglycemia induces damage of vascular endothelial cells leading to diabetic complications. We investigated the effects of insulinotropic compounds and elevated glucose on endothelial cells in the absence or presence of vascular endothelial growth factor (VEGF). Results Human umbilical vein endothelial cells (HUVECs) were treated with glibenclamide, repaglinide and insulinotropic imidazolines at high glucose concentration in the presence or absence of VEGF and viability, proliferation and nitric oxide production were measured. Hyperglycemia inhibited pro-survival effects of VEGF on endothelial cells. Glibenclamide and repaglinide decreased HUVEC viability at elevated glucose concentration in the absence but not in the presence of VEGF, without affecting HUVEC proliferation. Repaglinide also had some positive influence on HUVEC function elevating NO production in the presence of VEGF. Imidazolines showed different activities on endothelial cell survival. Efaroxan diminished HUVEC viability at elevated glucose concentration in the presence, however not in the absence of VEGF, while RX871024 decreased HUVEC survival regardless of the presence of VEGF. Significance of the study Our data demonstrate an important interplay between the actual insulinotropic compounds, VEGF and ambient glucose concentration affecting the survival of the vascular endothelial cells. Consequently, this interplay needs to be taken into consideration when designing novel oral antidiabetic compounds. [ABSTRACT FROM AUTHOR]

Populations of Indo-Pacific bottlenose dolphin (Tursiops aduncus) are distributed along coastal regions of the south-west Indian Ocean (SWIO), from South Africa to Kenya. An account of whistles from wild T. aduncus inhabiting the SWIO is provided here. Recordings were made at Plettenberg Bay (South Africa) and Zanzibar Island (Tanzania) and the frequency trace of whistle contours (n = 1677) was extracted. Multiple parameters were measured from each whistle and compared between regions and encounters. Regional variation was significant in all parameters assessed except for start and middle frequency (frequency at half the duration). Whistles from Zanzibar Island ended on average 4 kHz higher than those from Plettenberg Bay, and had a steeper frequency gradient. However, mean frequencies differed by <1 kHz and population averages for the adopted frequency distribution showed similar patterns, with a peak between 5 and 7 kHz. Whistle parameters were strongly influenced by recording encounter, likely reflecting the presence of different individuals, group compositions and behavioral contexts during recording occasions. Comparisons within the genus showed that T. aduncus from the SWIO have amongst the lowest start and minimum frequency of whistles within Tursiops. [ABSTRACT FROM AUTHOR]

Abstract: In a previous review for Advances in Enzyme Research () we outlined the history of our involvement in discovering important roles for inositides in the insulin secreting pancreatic beta cell. In this current appraisal we bring the work up to date and project how we believe this field will continue to develop in the future. Recently, we have seen an important synergism between the growth in our understanding of inositide function and our knowledge of beta cell stimulus-secretion coupling in both physiological and pathophysiological contexts. Important advances have been made in three areas. 1. The classic regulation of cytoplasmic free Ca2+ concentration [Ca2+]i by Inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3) and its receptor, 2. A novel role of the inositol pyrophosphates, especially 5-diphosphoinositol pentakisphosphate (5-PP-InsP 5), in exocytosis, and 3. The unique signaling roles of PI3K pathways instituted by the engagement of the insulin receptor in an autocrine, positive feed-back loop. We examine each of these in turn and close with an assessment of the likely future directions the research will take. [Copyright &y& Elsevier]

The article focuses on the records of marine mammals in Tanzania undertaken by the Marine Mammal Education and Research Group of the Institute of Marine Sciences in Roatan, Honduras in 1998. It mentions that most of the information on marine mammals was collected off the coast of Unguja Island and data gathering is undertaken through sampling procedure of strandings and bycatch marine mammals. The results show that from 1992 to 2008, 22 marine mammals were reported stranded. Moreover, the results also show that from January 2000 to December 2008, 213 bycatches and one dugong were reported.

Objective. To compare wireless with catheter-based esophageal pH recordings. Material and methods. Forty-five patients with symptoms suggestive of gastroesophageal reflux disease and 47 healthy volunteers were investigated in a university-affiliated hospital; 48-h wireless esophageal pH recording was performed. During the first 24 h, simultaneous traditional pH recording by catheter was undertaken. Nine of the volunteers underwent repeated measurements with both techniques. Outcome measures were feasibility, agreement, concordance of diagnostic yield, reproducibility, and subjective symptoms. Results. Subjective parameters were less affected when using the wireless technique alone (p<0.05). On using the wireless technique, esophageal acid exposure was underestimated approximately by half compared with traditional recording (p<0.05). Although pH data obtained with the two techniques were correlated (r2=0.66, p<0.001), the range between limits of agreement was wide (-3.7 to 10.0 percentage units of total time pH <4). Coefficients of variation for repeated measurements were 60.1±26.3% for catheter recordings, and 66.0±47.3 for wireless recordings on day 1 (NS). Concordance of diagnostic yield was 81.5% with all subjects included. Conclusions. Forty-eight-hour wireless Bravo pH monitoring is feasible but consistently underestimates esophageal acid exposure compared to the conventional technique. Although there is a significant correlation between the two techniques for pH recordings, the wide range in limits of agreement and the large coefficient of variation with both techniques suggest that the two methods are not immediately interchangeable for use in clinical practice. [ABSTRACT FROM AUTHOR]

Bycatches are considered the most serious threat to harbour porpoises (Phocoena phocoena) and other small cetaceans worldwide. Pingers are used to reduce bycatch levels, but may also deter porpoises from critical habitats. We investigated the spatial and temporal responses of porpoises to simulated bottom-set nets equipped with periodically operating Dukane NetMark 1000 pingers. Echolocation rates were monitored by porpoise click train detectors (PODs) placed at and around the nets, and a shore-based observation team recorded surfacing positions and movements. Pinger sound significantly reduced the median echolocation encounter rate by 50%–100% at PODs placed up to 500 m and reduced the sighting rate up to 375 m from the simulated net. The average distance of approach increased by 300 m. When pingers were silent after being active for 24 h 50 min, the return time of porpoises was 6 h, in comparison with 2.5 h after pingers had been silent. During the study period of approximately 50 days, habituation was detectable at two of nine PODs. The results indicate that pingers affect porpoises at greater distances than previously observed. This confirms that pingers are an effective bycatch mitigation measure, but alternative solutions should be applied in ecologically important habitats and migration routes. An example is given from the Baltic region. [ABSTRACT FROM AUTHOR]

Abstract: The stomach contents of 26 Indo-Pacific bottlenose dolphins (Tursiops aduncus) incidentally caught in gillnet fisheries around Unguja Island (Zanzibar) between February 2000 and August 2002 were examined. The relative importance of each prey species was assessed through indices of relative importance. In total, 1403 prey items comprising 50 species of bony fish and three species of squid were identified from food remains. Five species of fish, Uroconger lepturus, Synaphobranchus kaupii, Apogon apogonides, Lethrinus crocineus, Lutjanus fulvus, and three species of squid, Sepioteuthis lessoniana, Sepia latimanus and Loligo duvauceli, were the most important prey species. Based on an index that included frequency of occurrence, percentage by number and by weight, Uroconger lepturus proved to be the most important prey species of mature dolphins whereas Apogon apogonides was the preferred prey of immature dolphins. These results indicate that Indo-Pacific bottlenose dolphins off the coast of Zanzibar forage on a relatively large number of prey species, but that only a few small- and medium-sized neritic fish and cephalopods contribute substantially to the diet. Further, the ecology and behavior of the preferred fish prey species indicate that the dolphins forage over reef or soft bottom substrata and near the shore. [Copyright &y& Elsevier]

The β-cell is equipped with at least six voltage-gated Ca2+ (Cav) channel α1-subunits designated Cav1.2, Cav1.3, Cav2.1, Cav2.2, Cav2.3, and Cav3.1. These principal subunits, together with certain auxiliary subunits, assemble into different types of Cav channels conducting L-, P/Q-, N-, R-, and T-type Ca2+ currents, respectively. The β cell shares customary mechanisms of Cav channel regulation with other excitable cells, such as protein phosphorylation, Ca2+-dependent inactivation, and G protein modulation How ever, the β-cell displays some characteristic features to bring these mechanisms into play. In islet β-cells. Cav channels can be highly phosphorylated under basal conditions and thus marginally respond to further phosphorylation. In β-cell lines, Cav channels can be surrounded by tonically activated protein phosphatases dominating over protein kinases; thus their activity is dramatically enhanced by inhibition of protein phosphatases. During the last 10 years, we have revealed some novel mechanisms of β-cell Cav channel regulation under physiological and pathophysiological conditions, including the involvement of exocytotic proteins, inositol hexakisphosphate, and type 1 diabetic serum. This minireview highlights characteristic features of customary mechanisms of Cav channel regulation in β-cells and also reviews our studies on newly identified mechanisms of β-cell Cav channel regulation. [ABSTRACT FROM AUTHOR]

In this issue of the JCI, Ciampi et at. report the identification of a novel oncogene in patients affected by radiation-associated thyroid papillary carcinomas (see the related article beginning on page 94). This oncogene derives from a paracentric inversion of the long arm of chromosome 7, which results in an in-frame fusion of the N-terminus of the A-kinase anchor protein 9 (AKAP9) gene with the C-terminal catalytic domain (exons 9-18) of the serine-threonine kinase BRAF. The resulting AKAP9-BRAF fusion protein shows constitutive kinase activity, and it is able to transmit mitogenic signals to the MAPK pathways and to promote malignant transformation of NIH3T3 cells. [ABSTRACT FROM AUTHOR]

An oscillatory increase in pancreatic β cell cytoplasmic free Ca2+ concentration, [Ca2+]i, is a key feature in glucose-induced insulin release. The role of the voltage-gated Ca2+ channel β3 subunit in the molecular regulation of these [Ca2+]i oscillations has now been clarified by using β3 subunit-deficient β cells. β3 knockout mice showed a more efficient glucose homeostasis compared to wild-type mice due to increased glucose-stimulated insulin secretion. This resulted from an increased glucose-induced [Ca2+]i oscillation frequency in β cells lacking the β3 subunit, an effect accounted for by enhanced formation of inositol 1,4,5-trisphosphate (InsP3) and increased Ca2+ mobilization from intracellular stores. Hence, the β3 subunit negatively modulated InsP3-induced Ca2+ release, which is not paralleled by any effect on the voltage-gated L type Ca2+ channel. Since the increase in insulin release was manifested only at high glucose concentrations, blocking the β3 subunit in the β cell may constitute the basis for a novel diabetes therapy. [Copyright &y& Elsevier]

Inositolhexakisphosphate (InsP[sub 6]) plays a pivotal role in the pancreatic β-cell stimulus-secretion coupling. We have used capacitance measurements to study the effects of InsP[sub 6] on ca[sup 2+]-dependent exocytosis in single mouse pancreatic β-cells. In the presence of inhibitors of the protein phosphatase calcineurin to block endocytosis, intracellular application of InsP[sub 6] produced a dosedependent stimulation of exocytosis, and half-maximal effect was observed at 22 μM. The stimulatory effect of InsP[sub 6] was dependent on protein kinase C (PKC) activity. Antisense oligonucleotides directed against specific PKC isoforms (α, βII, δ, ∈, ξ) revealed the involvement of PKC-∈ in InsP[sub 6]-induced exocytosis. Furthermore, expression of dominant negative PKC-∈ abolished InsP[sub 6]evoked exocytosis, whereas expression of wild-type PKC-∈ led to a significant stimulation of InsP[sub 6]-induced exocytosis. These data demonstrate that PKC-∈ is involved in InsP[sub 6]-induced exocytosis in pancreatic β-cells. [ABSTRACT FROM AUTHOR]

A field experiment with Dukane NetMark™ 1000 pingers was conducted in the bottom-set gillnet fishery for cod in the Swedish Skagerrak Sea between March and April 1997. The aim of the experiment was to evaluate (i) the effectiveness of pingers to reduce by-catch rate of harbour porpoises, and (ii) the effects of pingers on the catches of the target species in the fishery. The design of the study was based on a statistical power analysis and the results from observer programmes conducted 1995–1996 in the same area, fishery and time of year.The catches of cod, pollack and other fish species were not affected by the sound of the pingers in the active strings. No harbour porpoise was caught in any control or active string, which was a significantly lower by-catch rate than in the two previous years. This could not be explained by a reduction in fishing effort per se, a difference in the total catch of fish for consumption or a shift in the spatial distribution of the sets between the observer programmes and the pinger experiment. However, the spatial analyses demonstrated that the experimental strings were set parallel to the coast and along the 50 m isobath, and that the audible range of the active pingers on average covered 16% of the longitudinal length and 5% of the surface area of the experimental fishing area. A compilation of herring landings by Swedish fishermen operating in the Skagerrak Sea 1995–1997 suggests that herring were more abundant in 1997 than in 1995. Good access to food in other parts of the porpoises'' distribution range and an aversive reaction to the ensonification could have caused their displacement in the fishing area.A displacement effect by pingers is likely to be more prominent in coastal waters where access to bodies of water is limited and the consequence may be serious if the area is critical to the survival of the porpoise population. Copyright 2002 International Council for the Exploration of the Sea. Published by Elsevier Science Ltd. All rights reserved. [Copyright &y& Elsevier]

Mitochondrial dynamics and bioenergetics are central to glucose-stimulated insulin secretion by pancreatic beta cells. Previously, we demonstrated that a disturbance in glucose-invoked fission impairs insulin secretion by compromising glucose catabolism. Here, we investigated whether the overexpression of mitochondrial fission regulator Drp1 in MIN6 cells can improve or rescue insulin secretion. Although Drp1 overexpression slightly improves the triggering mechanism of insulin secretion of the Drp1-knockdown cells and has no adverse effects on mitochondrial metabolism in wildtype MIN6 cells, the constitutive presence of Drp1 unexpectedly impairs insulin content, which leads to a reduction in the absolute values of secreted insulin. Coherent with previous studies in Drp1-overexpressing muscle cells, we found that the upregulation of ER stress-related genes (BiP, Chop, and Hsp60) possibly impacts insulin production in MIN6 cells. Collectively, we confirm the important role of Drp1 for the energy-coupling of insulin secretion but unravel off-targets effects by Drp1 overexpression on insulin content that warrant caution when manipulating Drp1 in disease therapy. [ABSTRACT FROM AUTHOR]

The authors focus on a study published in journal "Nature Medicine" related to noninvasively control of gene expression by the application of radiogenetics and magnetic field in mice. Topics discussed include use of nanoparticle to control transgene expression and glucose homeostasis in a diabetic mouse, activation of tethered TRPV1Ca2+ channel by iron nanoparticles through radio waves or magnetic field and conversion of oscillatory magnetic field in oscillatory pattern.

Aim: Mechanical ventilation (MV) results in diminished diaphragm size and strength, termed ventilator‐induced diaphragm dysfunction (VIDD). VID increases dependence, prolongs weaning, and increases discharge mortality rates. The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is implicated in VIDD, upregulated following MV. JAK/STAT inhibition alleviates chronic muscle wasting conditions. This study aimed to explore the therapeutic potential of Ruxolitinib, an FDA approved JAK1/2 inhibitor (JI) for the treatment of VIDD. Methods: Rats were subjected to 5 days controlled MV (CMV) with and without daily Ruxolitinib gavage. Muscle fiber size and function were assessed. RNAseq, mitochondrial morphology, respirometry, and mass spectrometry were determined. Results: CMV significantly reduced diaphragm size and specific force by 45% (p < 0.01), associated with a two‐fold P‐STAT3 upregulation (p < 0.001). CMV disrupted mitochondrial content and reduced the oxygen consumption rate (p < 0.01). Expression of the motor protein myosin was unaffected, however CMV alters myosin function via post‐translational modifications (PTMs). Daily administration of JI increased animal survival (40% vs. 87%; p < 0.05), restricted P‐STAT3 (p < 0.001), and preserved diaphragm size and specific force. JI was associated with preserved mitochondrial content and respiratory function (p < 0.01), and the reversal or augmentation of myosin deamidation PTMs of the rod and head region. Conclusion: JI preserved diaphragm function, leading to increased survival in an experimental model of VIDD. Functional enhancement was associated with maintenance of mitochondrial content and respiration and the reversal of ventilator‐induced PTMs of myosin. These results demonstrate the potential of repurposing Ruxolitinib for treatment of VIDD. [ABSTRACT FROM AUTHOR]

It is well known that type-2 diabetes mellitus (T2D) is increasing worldwide, but also the autoimmune form, type-1 diabetes (T1D), is affecting more people. The latest estimation from the International Diabetes Federation (IDF) is that 1.1 million children and adolescents below 20 years of age have T1D. At present, we have no primary, secondary or tertiary prevention or treatment available, although many efforts testing different strategies have been made. This review is based on the findings that apolipoprotein CIII (apoCIII) is increased in T1D and that in vitro studies revealed that healthy β-cells exposed to apoCIII became apoptotic, together with the observation that humans with higher levels of the apolipoprotein, due to mutations in the gene, are more susceptible to developing T1D. We have summarized what is known about apoCIII in relation to inflammation and autoimmunity in in vitro and in vivo studies of T1D. The aim is to highlight the need for exploring this field as we still are only seeing the top of the iceberg. [ABSTRACT FROM AUTHOR]

The article reports on the link of Sirt1, an enzyme having the capacity to remove acetyl groups from specific nuclear proteins, to the regulation of aging. The enzyme is able to control glucose metabolism by serving as a sensor of the metabolic status in the hepatocytes. It regulates the activity of a variety of transcription factors and transcriptional coregulators. Sirt1 modulates aging and may consequently serve as a key decoder that translates caloric restriction to increase lifespan.

In an open letter published in 2002 in the "New York Times", 21 distinguished scientists criticized Japan's program of scientific research whaling, noting its poor design and unjustified reliance upon lethal sampling. In a Forum article in "BioScience," Aron, Burke, and Freeman castigate the letter's signers and accuse them of meddling in political issues without sufficient knowledge of the science involved in those issues. As members of the Scientific Committee (SC) of the International Whaling Commission (IWC), we can attest that the signers of the open letter correctly summarized criticisms made by researchers very familiar with Japanese scientific whaling. One such critique was presented and discussed last year at a meeting of the SC. It was authored by SC members representing a broad range of countries, yet mention of this paper and others like it was absent from Aron and his colleagues' commentary, betraying a selectiveness that pervades their article. The authors quote lines from SC reports to support their contention that the IWC regards scientific whaling as valuable, but they fail to acknowledge many other sections that are highly critical of the Japanese program. Japan's scientific whaling program in the North Pacific (JARPN) was originally described as a feasibility study, but it included no performance measures by which to judge its success or failure. Fundamental problems of the JARPN II study include a lack of testable hypotheses or performance measures; inappropriate use of ecosystem models and failure to include sensitivity analyses and key data on other ecosystem components; selective or inappropriate use of data or methods in estimating whale abundance; unnecessary reliance on lethal sampling; inappropriate geographic sampling for population structure analysis; and unrealistic assessments of the effect of the proposed catches on the populations concerned.

Fisheries by‐catch poses the single greatest threat to cetacean (whales, dolphins and porpoises) populations. Despite this, by‐catch of cetaceans does not receive proportionate levels of research or management effort. The contribution of small‐scale fisheries to cetacean by‐catch is generally overlooked because of the extreme data paucity in these fisheries. Here, we assess the likely geographic distribution of by‐catch risk posed to the odontocetes (toothed whales) at the global scale. We combine species' occurrence and estimates of fisheries susceptibility for all 72 marine toothed whale species with estimates of small‐scale fisheries' gillnet fishing pressure across 163 marine fishing nations. We show that the by‐catch risk from small‐scale fisheries is likely greatest in low‐ and middle‐income regions, generally in the tropics and sub‐tropics. Our findings highlight a "wicked problem", that the highest by‐catch risks primarily occur in regions with lowest fisheries management efficacy. Addressing by‐catch in these priority regions is fraught with potentially damaging consequences for the survival of vulnerable human coastal communities. Yet, immediate management and conservation actions are required to prevent species extirpation and extinction through the reduction of small‐scale fisheries by‐catch. To be successful, these actions will likely require multilateral cooperation and must carefully balance both species and human needs. [ABSTRACT FROM AUTHOR]

By‐catch is the primary global conservation threat to populations of dolphins and porpoises. Despite protection for these protected species under its Habitats Directive, the European Union (EU) has failed to adequately assess and, where necessary, mitigate the by‐catch of small cetaceans. Management authority is diffuse, and the EU has no over‐arching, quantitative conservation objectives. To address this, we recommend that the EU adopt a comprehensive plan to conserve dolphins and porpoises in European waters. This plan should include regular formal assessments of small cetacean populations, including establishment of quantitative management objectives, generation of estimates of abundance and by‐catch mortality, and agreement on biological reference points that will guide management actions to ensure that by‐catch does not exceed sustainable levels. [ABSTRACT FROM AUTHOR]

The Harbour porpoise (Phocoena phocoena) is a highly mobile cetacean species primarily occurring in coastal and shelf waters across the Northern hemisphere. It inhabits heterogeneous seascapes broadly varying in salinity and temperature. Here, we produced 74 whole genomes at intermediate coverage to study Harbour porpoise's evolutionary history and investigate the role of local adaptation in the diversification into subspecies and populations. We identified ~6 million high quality SNPs sampled at eight localities across the North Atlantic and adjacent waters, which we used for population structure, demographic and genotype–environment association analyses. Our results suggest a genetic differentiation between three subspecies (P.p. relicta, P.p. phocoena and P.p. meridionalis), and three distinct populations within P.p. phocoena: Atlantic, Belt Sea and Proper Baltic Sea. Effective population size and Tajima's D suggest population contraction in Black Sea and Iberian porpoises, but expansion in the P.p. phocoena populations. Phylogenetic trees indicate post‐glacial colonization from a southern refugium. Genotype–environment association analysis identified salinity as major driver in genomic variation and we identified candidate genes putatively underlying adaptation to different salinity. Our study highlights the value of whole genome resequencing to unravel subtle population structure in highly mobile species, shows how strong environmental gradients and local adaptation may lead to population differentiation, and how neutral and adaptive markers can give different perspectives on population subdivision. The results have great conservation implications as we found inbreeding and low genetic diversity in the endangered Black Sea subspecies and identified the critically endangered Proper Baltic Sea porpoises as a separate population. [ABSTRACT FROM AUTHOR]

Multiple inositol polyphosphate phosphatase (MINPP1) is an enigmatic enzyme that is responsible for the metabolism of inositol hexakisphosphate (InsP6) and inositol 1,3,4,5,6 pentakisphosphate (Ins(1,3,4,5,6)P5 in mammalian cells, despite being restricted to the confines of the ER. The reason for this compartmentalization is unclear. In our previous studies in the insulin-secreting HIT cell line, we expressed MINPP1 in the cytosol to artificially reduce the concentration of these higher inositol phosphates. Undocumented at the time, we noted cytosolic MINPP1 expression reduced cell growth. We were struck by the similarities in substrate preference between a number of different enzymes that are able to metabolize both inositol phosphates and lipids, notably IPMK and PTEN. MINPP1 was first characterized as a phosphatase that could remove the 3-phosphate from inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4). This molecule shares strong structural homology with the major product of the growth-promoting Phosphatidyl 3-kinase (PI3K), phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and PTEN can degrade both this lipid and Ins(1,3,4,5)P4. Because of this similar substrate preference, we postulated that the cytosolic version of MINPP1 (cyt-MINPP1) may not only attack inositol polyphosphates but also PtdIns(3,4,5)P3, a key signal in mitogenesis. Our experiments show that expression of cyt-MINPP1 in HIT cells lowers the concentration of PtdIns(3,4,5)P3. We conclude this reflects a direct effect of MINPP1 upon the lipid because cyt-MINPP1 actively dephosphorylates synthetic, di(C4:0)PtdIns(3,4,5)P3 in vitro. These data illustrate the importance of MINPP1′s confinement to the ER whereby important aspects of inositol phosphate metabolism and inositol lipid signaling can be separately regulated and give one important clarification for MINPP1′s ER seclusion. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) imaging and ultrasound experimental measurements were combined to reconstruct the acoustic properties (density, velocity, and impedance) of the head from a deceased Indo-Pacific humpback dolphin (Sousa chinensis). The authors extracted 42 soft forehead tissue samples to estimate the sound velocity and density properties at room temperature, 25.0  °C. Hounsfield Units (HUs) of the samples were read from CT scans. Linear relationships between the tissues' HUs and velocity, and HUs and density were revealed through regression analyses. The distributions of the head acoustic properties at axial, coronal, and sagittal cross sections were reconstructed, suggesting that the forehead soft tissues were characterized by low-velocity in the melon, high-velocity in the muscle and connective tissues. Further, the sound velocities of melon, muscle, and connective tissue pieces were measured under different temperatures to investigate tissues' velocity response to temperature. The results demonstrated nonlinear relationships between tissues' sound velocity and temperature. This study represents a first attempt to provide general information on acoustic properties of this species. The results could provide meaningful information for understanding the species' bioacoustic characteristics and for further investigation on sound beam formation of the dolphin. [ABSTRACT FROM AUTHOR]

Apolipoprotein CIII (apoCIII) is increased in obesity‐induced insulin resistance and type‐2 diabetes. Emerging evidences support the advantages of small interfering RNAs (siRNAs) to target disease‐causing genes. The aim of this study was to develop siRNAs for in vivo silencing of apoCIII and investigate if this results in metabolic improvements comparable to what we have seen using antisense oligonucelotides against apoCIII. Twenty‐four siRNAs were synthesized and tested in a dual luciferase reporter assay. The eight best were selected, based on knockdown at 20 nM, and of these, two were selected based on IC50 values. In vivo experiments were performed in ob/ob mice, an obese animal model for diabetes. To determine the dose‐dependency, efficacy, duration of effect and therapeutic dose we used a short protocol giving the apoCIII‐siRNA mix for three days. To evaluate long‐term metabolic effects mice were treated for three days, every second week for eight weeks. The siRNA mix effectively and selectively reduced expression of apoCIII in liver in vivo. Treatment had to be repeated every two weeks to maintain a suppression of apoCIII. The reduction of apoCIII resulted in increased LPL activity, lower triglycerides, reduced liver fat, ceased weight gain, enhanced insulin sensitivity, and improved glucose homeostasis. No off‐target or side effects were observed during the eight‐week treatment period. These results suggest that in vivo silencing of apoCIII with siRNA, is a promising approach with the potential to be used in the battle against obesity‐induced metabolic disorders. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Conservation genetics without knowing what to conserve: the case of the Baltic harbour porpoise Phocoena Phocoena," by A. Palmé and colleagues, in a 2008 issue.

Obligate coral feeders such as many members of the Chaetodontidae family (also known as butterflyfish) often show strong preferences for particular coral species. This is thought to have evolved through natural selection as an energy-maximising strategy. Although some species remain as highly specialised feeders throughout their lifetime, many corallivores show a degree of dietary versatility when food abundance is limited; a strategy described by the optimal foraging theory. This study aimed to examine if, within-reef differences in the feeding regime and territory size of the Triangle Butterflyfish Chaetodon triangulum occurred, as a function of resource availability. Results showed that the dietary specialisation of C. triangulum was significant in both areas of low and high coral cover (χL22 = 2.52 x 102, P<0.001 and χL22 = 3.78 x 102, P<0.001 respectively). Resource selection functions (RSFs), calculated for the two main sites of contrasting coral assemblage, showed that in the resource-rich environments, only two Genera (Acropora and Pocillopora) were preferentially selected for, with the majority of other corals being actively ‘avoided’. Conversely, in territories of lower coral coverage, C. triangulum was being less selective in its prey choice and consuming corals in a more even distribution with respect to their availability. Interestingly, coral cover appeared to show no significant effect on feeding rate, however it was a primary determinant of territory size. The findings of the study agree with the predictions of the optimal foraging theory, in that where food supply is scarce, dietary specialisation is minimised and territory size increased. This results in maximising energy intake. This study represents the first scientific evidence that C. triangulum is an obligate corallivore and, as with many other butterflyfish, is therefore dependent on healthy scleractinian corals for survival. [ABSTRACT FROM AUTHOR]

Endocytosis is controlled by a well-orchestrated molecular machinery, where the individual players as well as their precise interactions are not fully understood. We now show that syndapin I/PACSIN 1 is expressed in pancreatic β cells and that its knockdown abrogates β cell endocytosis leading to disturbed plasma membrane protein homeostasis, as exemplified by an elevated density of L-type Ca2+ channels. Intriguingly, inositol hexakisphosphate (InsP6) activates casein kinase 2 (CK2) that phosphorylates syndapin I/PACSIN 1, thereby promoting interactions between syndapin I/PACSIN 1 and neural Wiskott–Aldrich syndrome protein (N-WASP) and driving β cell endocytosis. Dominant-negative interference with endogenous syndapin I/PACSIN 1 protein complexes, by overexpression of the syndapin I/PACSIN 1 SH3 domain, decreases InsP6-stimulated endocytosis. InsP6 thus promotes syndapin I/PACSIN 1 priming by CK2-dependent phosphorylation, which endows the syndapin I/PACSIN 1 SH3 domain with the capability to interact with the endocytic machinery and thereby initiate endocytosis, as exemplified in β cells. [ABSTRACT FROM AUTHOR]

Underwater noise levels may be strongly influenced by sea ice. This study presents systematic measurements of under-ice ambient noise levels in shallow (<30 m) coastal waters using passive acoustic technology. Acoustic data were collected at 6 sites with different ice concentration (two levels: incomplete and complete ice cover) and thickness (three levels: <10 cm, 10–20 cm and >20 cm) in Liaodong Bay, China. Wind (max = 5.3 m/s) and current (max = 0.3 m/s) conditions were very weak, making minimal contributions to under-ice noise in this study. Root-mean-squared broadband (20–10,000 Hz) noise levels (BNLs) and one-third-octave-band noise levels (TOLs) at 63, 125 and 2000 Hz were measured. Median BNLs of the 6 recording sites ranged from 104.5 to 129.1 dB re 1 μPa, and median TOLs at 63, 125 and 2000 Hz were between 76.5 and 118.0 dB re 1 μPa at the 6 sites. Generalized Linear Models were used to analyze broadband and three one-third-octave-band noise levels in different ice concentration and thickness levels. The results showed that, regardless of the ice thickness, the sites with incomplete ice concentration had higher BNLs and 63, 125 and 2000 Hz TOLs than the sites with complete ice concentration, and regardless of the ice concentration, both BNLs and all three TOLs decreased with increased ice thickness. This study provides baseline characterization of under-ice noise in shallow coastal waters and indicating that both ice concentration and thickness have significant influence on the under-ice noise levels. These findings are important for future studies investigating acoustic communication and noise pollution in shallow coastal waters with sea ice. - First systematic measurement of under-ice noise levels for shallow coastal waters. - Ice concentration and thickness significantly influence under-ice noise levels. - Areas with incomplete ice cover or thinner ice thickness had higher noise levels. - The results are crucial for future noise pollution studies in sea ice environments. [ABSTRACT FROM AUTHOR]

Western-type diets are linked to obesity and diabetes partly because of their high-saturated fatty acid (SFA) content. We found that SFAs, but not unsaturated fatty acids (USFAs), reduced lipid droplets (LDs) within pancreatic ß cells. Mechanistically, SFAs, but not USFAs, reduced LD formation by inducing S-acylation and proteasomal, mediated degradation of fat storage-inducing transmembrane protein 2 (FIT2), an endoplasmic reticulum (ER) resident protein important for LD formation. Targeted ablation of FIT2 reduced ß cell LD numbers, lowered ß cell ATP levels, reduced Ca2+ signaling, dampened vesicle exocytosis, down-regulated ß cell transcription factors, up-regulated unfolded protein response genes, and finally, exacerbated diet-induced diabetes in mice. Subsequent mass spectrometry studies revealed increased C16:0 ceramide accumulation in islets of diet-induced diabetes mice lacking ß cell FIT2. Inhibition of ceramide synthases ameliorated the enhanced ER stress and improved insulin secretion. FIT2 was reduced in mouse diabetic islets, and separately, overexpression of FIT2 increased the number of intracellular LDs and rescued SFA-induced ER stress and apoptosis, thereby highlighting the protective role of FIT2 and LDs against ß cell lipotoxicity. [ABSTRACT FROM AUTHOR]

Highlights: [•] Robust abundance estimates for five cetacean species in EU Atlantic shelf waters. [•] No evidence for large-scale change in abundance between 1994 and 2005 in 3 species. [•] Large shift in harbour porpoise distribution demonstrated by spatial modelling. [•] Results allow assessment of conservation status at large spatial scale. [Copyright &y& Elsevier]

Apolipoprotein CIII (apoCIII) is proinflammatory and increases in high-fat diet (HFD)-induced obesity and insulin resistance. We have previously shown that reducing apoCIII improves insulin sensitivity in vivo by complex mechanisms involving liver and brown adipose tissue. In this study the focus was on subcutaneous (SAT) and visceral (VAT) white adipose tissue (WAT). Mice were either given HFD for 14 weeks and directly from start also treated with antisense oligonucleotide (ASO) against apoCIII or given HFD for 10 weeks and HFD+ASO for an additional 14 weeks. Both groups had animals treated with inactive (Scr) ASO as controls and in parallel chow-fed mice were injected with saline. Preventing an increase or lowering apoCIII in the HFD-fed mice decreased adipocytes' size, reduced expression of inflammatory cytokines and increased expression of genes related to thermogenesis and beiging. Isolated adipocytes from both VAT and SAT from the ASO-treated mice had normal insulin-induced inhibition of lipolysis compared to cells from Scr-treated mice. In conclusion, the HFD-induced metabolic derangements in WATs can be prevented and reversed by lowering apoCIII. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a multifactorial and polygenetic disease, although its exact etiology remains poorly understood. The objective of this study was to identify key biomarkers and potential molecular mechanisms in the development of T2D. Human RNA-Seq datasets across different tissues (GSE18732, GSE41762, and GSE78721) were collected from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) between T2D and controls were identified using differential analysis. A total of 90 overlapping DEGs were identified, among which YTHDF2 , DDX21 , and MDM2 were considered as key genes due to their central positions in the PPI network and the same regulatory pattern in T2D. Logistic regression analysis showed that low expression of the key genes increased the risk of T2D. Enrichment analysis revealed that the key genes are involved in various important biological functions and signaling pathways including Notch, Fork head box O (FOXO), and phosphoinositide 3-kinase (PI3K)-Akt. RT-qPCR and Western blot analysis showed that all three key genes were down-regulated in pancreatic islets of both prediabetic and diabetic mouse models. Finally, the insulin-sensitizer, pioglitazone was used to treat db/db mice and immunofluorescence analysis showed that the expression of all three key genes was significantly down-regulated in db/db islets, an effect that was overcome by pioglitazone treatment. Together, these results suggest that the identified key genes could be involved in the development of T2D and serve as potential biomarkers and therapeutic targets for this disease. • MDM2, YTHDF2 and DDX21 are potential biomarkers for predicting T2D. • MDM2, YTHDF2 and DDX21 are down-regulated in islets of T2D animals. • Down-regulation of MDM2, YTHDF2 and DDX21 in islets of T2D mice can be restored by pioglitazone treatment. [ABSTRACT FROM AUTHOR]

ATP-sensitive K+ (KATP) channels couple cellular metabolism to electrical activity in many cell types. Wild-type KATP channels are comprised of four pore forming (Kir6.x) and four regulatory (sulfonylurea receptor, SURx) subunits that each contain RKR endoplasmic reticulum retention sequences that serve to properly translocate the channel to the plasma membrane. Truncated Kir6.x variants lacking RKR sequences facilitate plasma membrane expression of functional Kir6.x in the absence of SURx; however, the effects of channel truncation on plasma membrane orientation have not been explored. To investigate the role of truncation on plasma membrane orientation of ATP sensitive K+ channels, three truncated variants of Kir6.2 were used (Kir6.2ΔC26, 6xHis-Kir6.2ΔC26, and 6xHis-EGFP-Kir6.2ΔC26). Oocyte expression of Kir6.2ΔC26 shows the presence of a population of inverted inserted channels in the plasma membrane, which is not present when co-expressed with SUR1. Immunocytochemical staining of intact and permeabilized HEK293 cells revealed that the N-terminus of 6xHis-Kir6.2ΔC26 was accessible on both sides of the plasma membrane at roughly equivalent ratios, whereas the N-terminus of 6xHis-EGFP-Kir6.2Δ26 was only accessible on the intracellular face. In HEK293 cells, whole-cell electrophysiological recordings showed a ca. 50% reduction in K+ current upon addition of ATP to the extracellular solution for 6xHis-Kir6.2ΔC26, though sensitivity to extracellular ATP was not observed in 6xHis-EGFP-Kir6.2ΔC26. Importantly, the population of channels that is inverted exhibited similar function to properly inserted channels within the plasma membrane. Taken together, these data suggest that in the absence of SURx, inverted channels can be formed from truncated Kir6.x subunits that are functionally active which may provide a new model for testing pharmacological modulators of Kir6.x, but also indicates the need for added caution when using truncated Kir6.2 mutants. [ABSTRACT FROM AUTHOR]

Abstract: Over the last two decades we have focused on beta cell signal transduction, bringing many new insights, especially in the context of insulin signal transduction, the role of inositol polyphosphates and the regulation of cytoplasmic free Ca2+ concentration. However, there has been a growing awareness that the beta cell, which is mandatory for insulin secretion, has a unique context within the micro-organ of the pancreatic Islet of Langerhans. In this environment the beta cell both mediates and receives paracrine regulation, critical for the control of blood glucose homeostasis. Failure of an appropriate beta cell function leads to the development of diabetes mellitus. In our quest to understand the molecular events maintaining beta cell function we have faced two key challenges. Firstly, whilst there are many similarities between signal transduction in pancreatic islets between the much used rodent models and humans there are some notable differences. Critical distinctions between rodent and primate can be made in the structure of the islet, including the arrangement of the islet cells, the innervation pattern and the microcirculation. This means that important signaling interactions between islets cells, mediated through for example insulin, glucagon, GABA, glutamate and ATP, will have a unique human framework. The second challenge was to be able to take the discoveries we have made using in vitro systems and examine them in an in vivo context. Advances in in vivo imaging achieved by utilizing the anterior chamber of the eye as a transplantation site for pancreatic islets make it possible for non-invasive, longitudinal studies at single cell resolution in real time of islet cell physiology and pathology. Thus it is becoming possible to study the insulin secreting pancreatic beta cell within the framework of the unique micro-organ, the Islet of Langerhans, for the first time in a physiological context, i.e. when being innervated and connected to the blood supply. [Copyright &y& Elsevier]

Sveegaard, S., Teilmann, J., Berggren, P., Mouritsen, K. N., Gillespie, D., and Tougaard, J. 2011. Acoustic surveys confirm the high-density areas of harbour porpoises found by satellite tracking. – ICES Journal of Marine Science, 68: 929–936.The population status of the harbour porpoise (Phocoena phocoena) has long been of concern in European waters. Consequently, the European Commission (EC) Habitats Directive obligates all EC member states to designate marine protected areas (MPAs) for harbour porpoises before 2012. These will be designated areas having the greatest density of porpoises. However, little is known about comparability between the monitoring methods used to examine porpoise distribution and density, and conflicting results may arise, especially when considering their varying sample size and temporal and spatial scales. Here, vessel-based acoustic surveys are seen as an independent method of testing the temporal and spatial permanence of previously identified areas of high density of harbour porpoises found by satellite-tracking them in inner Danish waters. Based on six acoustic surveys, a strong spatial accord was found between the number of acoustic detections of harbour porpoises and their density distribution obtained from 10 years of satellite tracking. The results confirm the presence and permanence of areas of high density of porpoises and validate the two methods for identifying and monitoring future MPAs for the species. [ABSTRACT FROM PUBLISHER]

Abstract: Pancreatic β-cells release insulin in appropriate amounts in order to keep blood glucose levels within physiological limits. Failure to do so leads to the most common metabolic disorder in man, diabetes mellitus. The glucose-stimulus/insulin-secretion coupling represents a sophisticated interplay between glucose and a variety of modulatory factors. These factors are provided by the blood supply (such as nutrients, vitamins, incretins etc.), the nerval innervations, cell-cell contacts as well as by paracrine and autocrine feedback loops within the pancreatic islet of Langerhans. However, the underlying mechanisms of their action remain poorly understood. In the present mini-review we discuss novel aspects of selective insulin signaling in the β-cell and novel insights into the role of higher inositol phosphates in insulin secretion. Finally we present a newly developed experimental platform that allows non-invasive and longitudinal in vivo imaging of pancreatic islet/β-cell biology at single-cell resolution. [Copyright &y& Elsevier]

The appropriate function of insulin-producing pancreatic β-cells is crucial for the regulation of glucose homeostasis, and its impairment leads to diabetes mellitus, the most common metabolic disorder in man. In addition to glucose, the major nutrient factor, inputs from the nervous system, humoral components, and cell-cell communication within the islet of Langerhans act together to guarantee the release of appropriate amounts of insulin in response to changes in blood glucose levels. Data obtained within the past decade in several laboratories have revitalized controversy over the autocrine feedback action of secreted insulin on β-cell function. Although insulin historically has been suggested to exert a negative effect on β-cells, recent data provide evidence for a positive role of insulin in transcription, translation, ion flux, insulin secretion, proliferation, and β-cell survival. Current insights on the role of insulin on pancreatic β-cell function are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Insulin secretion from pancreatic β-cells has to be tightly regulated to ensure accurate glucose homeostasis. The capacity of β-cells to respond to extracellular stimulation is determined by several signaling pathways. One important feature of these pathways is phosphorylation and subsequent dephosphorylation of a wide range of cellular substrates. Protein phosphatase 1 (PP1) is a major eukaryotic serine/threonine protein phosphatase that controls a multitude of physiological processes. We have investigated the expression and cellular distribution of two endogenous inhibitors of PP1 activity in β-cells. RT-PCR, Western blotting, and immunohistochemistry showed that DARPP-32 and inhibitor-1 are present in insulin-secreting endocrine β-cells. Subcellular fractionation of mouse islets revealed that both PP1 inhibitors predominantly localized to cytosol-enriched fractions. Inhibitor-1 was also present in fractions containing plasma membrane-associated proteins. These data indicate a potential role for DARPP-32 and inhibitor-1 in the regulation of PP1 activity in pancreatic β-cell stimulus-secretion coupling. [Copyright &y& Elsevier]

ABSTRACT 1. Mixed species groups have long been noted in birds, but they also occur among different species of mammals ranging from closely related species to species from different orders. Mixed species groups of mammals occur in many different habitats, e.g. ungulates on the savannah, primates in various types of forests and cetaceans in the oceans. Mixed species groups are very different in their duration, frequency, predominant activity and structure depending on the species interacting and the habitat they occur in. 2. Functional explanations for mixed species groups usually fall within two categories: foraging advantages and predator avoidance. However, there could also be other social and reproductive advantages of mixed species groups that could contribute to their formation and stability. The advantages do not have to be equally distributed between the participating species and can also vary according to season and the presence of predators. 3. It is important that all investigators of mixed species groups take their studies one step further after the naturalistic description and test the function and benefits of mixed species groups in order to give more strength to their conclusions. In this paper we review and discuss the function of mixed species groups in mammals and suggest an approach on how to investigate the function of such groups. [ABSTRACT FROM AUTHOR]

Hypoglycemic sulfonylureas such as glibenclamide have been widely used to treat type 2 diabetic patients for 40 yr, but controversy remains about their mode of action. The widely held view is that they promote rapid insulin exocytosis by binding to and blocking pancreatic β-cell ATP-dependent K[sup +] (K[sub ATP]) channels in the plasma membrane. This event stimulates Ca[sup 2+] influx and sets in motion the exocytotic release of insulin. However, recent reports show that >90% of glibenclamide-binding sites are localized intracellularly and that the drug can stimulate insulin release independently of changes in K[sub ATP] channels and cytoplasmic free Ca[sup 2+]. Also, glibenclamide specifically and progressively accumulates in islets in association with secretory granules and mitochondria and causes long-lasting insulin secretion. It has been proposed that nutrient insulin secretagogues stimulate insulin release by increasing formation of malonyl-CoA, which, by blocking carnitine palmitoyltransferase 1 (CPT-1), switches fatty acid (FA) catabolism to synthesis of PKC-activating lipids. We show that glibenclamide dose-dependently inhibits β-cell CPT-1 activity, consequently suppressing FA oxidation to the same extent as glucose in cultured fetal rat islets. This is associated with enhanced diacylglycerol (DAG) formation, PKC activation, and K[sub ATP]-independent glibenclamide-stimulated insulin exocytosis. The fat oxidation inhibitor etomoxir stimulated K[sub ATP]-independent insulin secretion to the same extent as glibenclamide, and the action of both drugs was not additive. We propose a mechanism in which inhibition of CPT-1 activity by glibenclamide switches β-cell FA metabolism to DAG synthesis and subsequent PKC-dependent and K[sub ATP]-independent insulin exocytosis. We suggest that chronic CPT inhibition, through the progressive islet accumulation of glibenclamide, may explain the prolonged stimulation of insulin secretion in some diabetic... [ABSTRACT FROM AUTHOR]

Pancreatic β-cell function is essential for the regulation of glucose homeostasis and its impairment leads to diabetes mellitus. Besides glucose, the major nutrient factor, inputs from neural and humoral components and intraislet cell–cell communication act together to guarantee an appropriate pancreatic β-cell function. Data obtained over the last 5 years in several laboratories have revitalized a controversial concept, namely the autocrine feedback action of secreted insulin on β-cell function. While, historically, insulin was suggested to exert a negative effect on β-cells, recent data provide evidence for a positive role of insulin in transcription, translation, ion flux, insulin secretion and β-cell survival. [Copyright &y& Elsevier]

The imidazoline RX871024 increased basal- and glucose-stimulated insulin release in vitro and in vivo. The compound inhibited activity of ATP-sensitive K(+) channels as well as voltage-gated K(+) channels, which led to membrane depolarization, an increase in the cytosolic Ca(2+) concentration ([Ca(2+)](i)), and insulin release. Importantly, RX871024 also enhanced the insulinotropic effect of glucose in cells with clamped [Ca(2+)](i) but in the presence of high ATP and Ca(2+)concentration inside the cell. We believe that the latter effect on insulin exocytosis was at least in part mediated by a rise in diacylglycerol, which then activated protein kinase C (PKC) and increased the generation of arachidonic acid (AA) metabolites. Activation of both the PKC and AA pathways resulted in potentiation of glucose effects on insulin secretion. Unlike RX871024, the novel imidazoline BL11282 did not block ATP-dependent K(+) channels, but similarly to RX871024, it stimulated insulin secretion in depolarized or permeabilized islets. Accordingly, BL11282 did not influence glucose and insulin levels under basal conditions either in vitro or in vivo, but it markedly enhanced the insulinotropic effects of glucose. BL11282 restored the impaired insulin response to glucose in islets from spontaneously diabetic GK rats. We conclude that BL11282 belongs to a new class of insulinotropic compounds that demonstrate a strong glucose-dependent effect on insulin exocytosis. [ABSTRACT FROM AUTHOR]

Fluorescent proteins have been extensively used as protein "tags" to study the subcellular localization of proteins and/or their translocation upon stimulation or as markers for transfection in transient and stable expression systems. However, they have not been frequently used as reporter genes to monitor stimulus-induced gene expression in mammalian cells. Here we demonstrate the use of fluorescent proteins to study stimulus-induced gene transcription. The general applicability of the approach is exemplified by doxycyclin-(Tet-On) and phorbol 12-myristate 13-acetate-induced (c-fos) promoter activation, with green fluorescent protein (GFP) and red fluorescent protein (DsRed) as semiquantitative and immediate reporters, of transcription activation. Under the control of beta-cell-specific promoters, such as the rat insulin 1 promoter or the rat upstream glucokinase promoter, this approach allowed us to monitor online glucose-induced gene transcription in primary beta-cells at the single-cell level as well as in the context of the islet of Langerhans. Applying discretely detectable fluorescent proteins, for example GFP and DsRed, enabled us to simultaneously monitor stimulus-induced transcription by two different promoters in the same cell. [ABSTRACT FROM AUTHOR]