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Since the discovery of glucagon 100 years ago, the hormone and the pancreatic islet alpha cells that produce it have remained enigmatic relative to insulin-producing beta cells. Canonically, alpha cells have been described in the context of glucagon’s role in glucose metabolism in liver, with glucose as the primary nutrient signal regulating alpha cell function. However, current data reveal a more holistic model of metabolic signalling, involving glucagon-regulated metabolism of multiple nutrients by the liver and other tissues, including amino acids and lipids, providing reciprocal feedback to regulate glucagon secretion and even alpha cell mass. Here we describe how various nutrients are sensed, transported and metabolised in alpha cells, providing an integrative model for the metabolic regulation of glucagon secretion and action. Importantly, we discuss where these nutrient-sensing pathways intersect to regulate alpha cell function and highlight key areas for future research., Since the discovery of glucagon 100 years ago, the hormone and the pancreatic islet alpha cells that produce it have remained enigmatic relative to insulin-producing beta cells. Canonically, alpha cells have been described in the context of glucagon's role in glucose metabolism in liver, with glucose as the primary nutrient signal regulating alpha cell function. However, current data reveal a more holistic model of metabolic signalling, involving glucagon-regulated metabolism of multiple nutrients by the liver and other tissues, including amino acids and lipids, providing reciprocal feedback to regulate glucagon secretion and even alpha cell mass. Here we describe how various nutrients are sensed, transported and metabolised in alpha cells, providing an integrative model for the metabolic regulation of glucagon secretion and action. Importantly, we discuss where these nutrient-sensing pathways intersect to regulate alpha cell function and highlight key areas for future research.

The "Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases" Workshop was a 1.5-day scientific conference at the National Institutes of Health (Bethesda, MD) that engaged clinical and basic science investigators interested in diseases of the pancreas. This report summarizes the workshop proceedings. The goal of the workshop was to forge connections and identify gaps in knowledge that could guide future research directions. Presentations were segregated into 6 major themes, including (a) Pancreas Anatomy and Physiology; (b) Diabetes in the Setting of Exocrine Disease; (c) Metabolic Influences on the Exocrine Pancreas; (d) Genetic Drivers of Pancreatic Diseases; (e) Tools for Integrated Pancreatic Analysis; and (f) Implications of Exocrine-Endocrine Crosstalk. For each theme, there were multiple presentations followed by panel discussions on specific topics relevant to each area of research; these are summarized herein. Significantly, the discussions resulted in the identification of research gaps and opportunities for the field to address. In general, it was concluded that as a pancreas research community, we must more thoughtfully integrate our current knowledge of the normal physiology as well as the disease mechanisms that underlie endocrine and exocrine disorders so that there is a better understanding of the interplay between these compartments.

Серед великої кількості захворювань органів травлення у домашніх тварин є панкреатит – запалення підшлункової залози, яке виникає внаслідок передчасної активації проферментів в ацинарних клітинах. Враховуючи прогресивне розповсюдження панкреатитів у домашніх тварин, у тому числі котів, актуальним питанням є дослідження структурної організації підшлункової залози у хворих тварин. Тому метою нашого дослідження було з’ясувати морфологічні зміни підшлункової залози котів за гострого панкреатиту. Під час даної роботи з хребетними тваринами керувалися «Європейською конвенцією із захисту хребетних тварин, які використовуються в експериментальних та інших наукових цілях» (Страсбург, 1986 р.). У результаті гістологічних досліджень підшлункової залози котів за гострого панкреатиту відмічали патогістологічні зміни як у екзокринній частині залози, так відповідно і у ендокринній. Такі зміни виражались значним некрозом екзокринної паренхіми залози, розширенням та набряком міжацинарного простору, що свідчило про початкову стадію розвитку запального процесу. У вогнищах некрозу тканини, виявляли дистрофічні змінами, які супроводжувались лізисом ядер. Цитоплазма панкреатоцитів була каламутна, базальні та апікальні її зони – нечіткі, відмічався виражений інтерстиційний набряк тканини між часточками та нерівномірний помірний набряк всередині часточок. Міжклітинні щілини були розширеними. Морфометрично у хворих тварин відзначали достовірне збільшення питомої ваги стромального компонента (р<0,05), що дорівнював – 22,44±0,24 % у контрольної групи він, відповідно, становив – 17,78±0,15 %. При гістологічному аналізі острівців Лангерганса, виявляли крововиливи та дистрофічно змінені гормонально-активні клітини та нерівномірний розподіл клітин. У більшості острівців, клітини мали набряклу вакуолізовану цитоплазму. При аналізі морфометричних показників відзначено, що екзокринна паренхіма підшлункової залози котів за гострого перебігу панкреатиту збільшувалась у 1,12 раза і становила 48258,05±1, From among a great number of digestive system diseases in domestic animals there is pancreatitis which is caused by an early zymogenesis in the acinar cells. The problem of studying the structural organization of a pancreata in sick cats is topical because of a progressive spreading of pancreatitis in domestic animals. Thus, the purpose of the research was to study out the morphological changes of cats pancreata under acute pancreatitis. Working with vertebrate animals we were guided by «European Convention for the Protection of Vertebtate Animals used for Experimental and other Scientific Purposes» (Strasbourg, 1986). The results of the histological examination of cats pancreata under acute pancreatitis show some pathological changes both in endocrine and exocrine pancreas. Such changes were manifested in necrosis of exocrine pancreatitis as well as in spreading and swelling of acinar space, that testified to the infancy of an inflammatory process. Some dystrophic changes, followed by karyolysis, were found in the focus of tissue nicrosis. Pancreatocyte cytoplasm was cloudy, its basal and apical zones were obscure, clearly defined interstitial tissue swelling was found between the particles and unequal swelling was found inside the particles. Intercellular space was exaggerated. Morphometrically in a group of sick animals was detected an increase in specific weihgt of stromal component (р<0,05),which equalled 22,44±0,24 %, in a control group it equalled 17,78±0,15 %. Some hemorrhage and distrophicvally changed hormone- active cells as well as nonregular distribution of cells were detected under a histological examination of Langerhans islets. In most islets the cells had swelled vacuolar cytoplasm. While analyzing the morphometric indices it was stated that the cats exocrine pancreas under acute pancreatitis was 1.12 as large and occupied 48258,05±135,07 mkm2, (97,88±0,05 %). The cats endocrine pancreas under this pathology occupied 6858,85±315,05 mkm2, (2,12±0,05, Среди большого количества заболеваний органов пищеварения у домашних животных является панкреатит - воспаление поджелудочной железы, которое возникает в результате преждевременной активации проферментов в ацинарных клетках. Учитывая прогрессивное распространение панкреатитов у домашних животных, в том числе кошек, актуальным вопросом является исследование структурной организации поджелудочной железы у больных животных. Поэтому целью нашего исследования было выяснить морфологические изменения поджелудочной железы котов за острого панкреатита. Во время данной работы с позвоночными животными руководствовались «Европейской конвенцией по защите позвоночных животных, используемых в экспериментальных и других научных целях» (Страсбург, 1986 г.). В результате гистологических исследований поджелудочной железы котов за острого панкреатита отмечали патогистологические изменения как в экзокринной части железы, так соответственно и в эндокринной. Такие изменения выражались значительным некрозом экзокринной паренхимы железы, расширением и отеком мижацинарного пространства, что свидетельствовало о начальной стадии развития воспалительного процесса. В очагах некроза ткани, проявляли дистрофические изменениями, которые сопровождались лизисом ядер. Цитоплазма панкреатоцитив была мутная, базальные и апикальные ее зоны - нечеткие, отмечался выраженный интерстициальный отек ткани между дольками и неравномерный умеренный отек внутри долек. Межклеточные щели были расширенными. Морфометрически у больных животных отмечали достоверное увеличение удельного веса стромального компонента (р <0,05), равный - 22,44 ± 0,24% в контрольной группе он, соответственно, составил - 17,78 ± 0,15%. При гистологическом анализе островков Лангерганса, проявляли кровоизлияния и дистрофически изменены гормонально-активные клетки и неравномерное распределение клеток. В большинстве островков, клетки имели набухшую вакуолизированную цитоплазму. При анализе морфометрических показателей отмечено, что экзокринная паре

Aquaglyceroporins are a group of the aquaporin (AQP) family of transmembrane water channels. While AQPs facilitate the passage of water, small solutes, and gases across biological membranes, aquaglyceroporins allow passage of water, glycerol, urea and some other solutes. Thanks to their glycerol permeability, aquaglyceroporins are involved in energy homeostasis. This review provides an overview of what is currently known concerning the functional implication and control of aquaglyceroporins in tissues involved in energy metabolism, i.e. liver, adipose tissue and endocrine pancreas. The expression, role and (dys)regulation of aquaglyceroporins in disorders affecting energy metabolism, and the potential relevance of aquaglyceroporins as drug targets to treat the alterations of the energy balance is also addressed., SCOPUS: re.j, info:eu-repo/semantics/published

Aim During pregnancy, the maternal beta-cell mass is increased in order to adapt to the physiological changes in insulin demand. Lactogenic hormones stimulate rodent beta-cell attachment and proliferation in vitro. The aim of this study was to identify adhesion molecules involved in expansion of the beta-cell mass during pregnancy in the rat.Methods Quantitative RT-PCR was used to evaluate the expression of several integrins and laminins in isolated neonatal rat islets in response to growth hormone (GH) and prolactin (PRL) treatment. Double-immunofluorescence staining of rat pancreas was used to localize the expression of integrin alpha 6 beta 1. beta-cell proliferation was evaluated by incorporation of bromodeoxyuridine (BrdU). The role of STAT5 phosphorylation was tested by addition of STAT5 mutants.Results We found that the mRNA level of integrin-alpha 6A, was upregulated 2.5-fold by PRL or GH. During pregnancy, a biphasic 3.4-4.5-fold increase of integrin-alpha 6A and B mRNA levels was detected. A disintegrin peptide (DP) reduced the hormone-stimulated mitotic activity in neonatal rat beta-cells from 2.9 +/- 0.4-fold to 1.3 +/- 0.3-fold. The hormone-induced expression of alpha 6 beta 1 integrin was shown to be mediated via STAT5 as a dominant negative (DN) mutant prevented and a constitutive active (CA) mutant augmented the hGH-stimulated expression. The DP was found to inhibit hGH-induced transactivation of the PRL receptor promoter 1A and reduce the hGH-induced phosphorylation of STAT5.Conclusion These results show that integrin-alpha 6 in beta-cells is upregulated by lactogenic hormones and is required but not sufficient for the expansion of the beta-cell mass in pregnancy in the rat, which may have implications for the understanding and treatment of gestational diabetes mellitus.

Aim During pregnancy, the maternal beta-cell mass is increased in order to adapt to the physiological changes in insulin demand. Lactogenic hormones stimulate rodent beta-cell attachment and proliferation in vitro. The aim of this study was to identify adhesion molecules involved in expansion of the beta-cell mass during pregnancy in the rat.Methods Quantitative RT-PCR was used to evaluate the expression of several integrins and laminins in isolated neonatal rat islets in response to growth hormone (GH) and prolactin (PRL) treatment. Double-immunofluorescence staining of rat pancreas was used to localize the expression of integrin alpha 6 beta 1. beta-cell proliferation was evaluated by incorporation of bromodeoxyuridine (BrdU). The role of STAT5 phosphorylation was tested by addition of STAT5 mutants.Results We found that the mRNA level of integrin-alpha 6A, was upregulated 2.5-fold by PRL or GH. During pregnancy, a biphasic 3.4-4.5-fold increase of integrin-alpha 6A and B mRNA levels was detected. A disintegrin peptide (DP) reduced the hormone-stimulated mitotic activity in neonatal rat beta-cells from 2.9 +/- 0.4-fold to 1.3 +/- 0.3-fold. The hormone-induced expression of alpha 6 beta 1 integrin was shown to be mediated via STAT5 as a dominant negative (DN) mutant prevented and a constitutive active (CA) mutant augmented the hGH-stimulated expression. The DP was found to inhibit hGH-induced transactivation of the PRL receptor promoter 1A and reduce the hGH-induced phosphorylation of STAT5.Conclusion These results show that integrin-alpha 6 in beta-cells is upregulated by lactogenic hormones and is required but not sufficient for the expansion of the beta-cell mass in pregnancy in the rat, which may have implications for the understanding and treatment of gestational diabetes mellitus.

Aquaporins (AQPs) are a family of transmembrane channel proteins facilitating the transport of water, small solutes, and gasses across biological membranes. AQPs are expressed in all tissues and ensure multiple roles under normal and pathophysiological conditions. Aquaglyceroporins are a subfamily of AQPs permeable to glycerol in addition to water and participate thereby to energy metabolism. This review focalizes on the present knowledge of the expression, regulation and physiological roles of AQPs in adipose tissue, liver and endocrine pancreas, that are involved in energy metabolism. In addition, the review aims at summarizing the involvement of AQPs in metabolic disorders, such as obesity, diabetes and liver diseases. Finally, challenges and recent advances related to pharmacological modulation of AQPs expression and function to control and treat metabolic diseases are discussed., SCOPUS: re.j, info:eu-repo/semantics/published

Activating germline mutations in STAT3 were recently identified as a cause of neonatal diabetes mellitus associated with beta-cell autoimmunity. We have investigated the effect of an activating mutation, STAT3(K392R,) on pancreatic development using induced pluripotent stem cells (iPSCs) derived from a patient with neonatal diabetes and pancreatic hypoplasia. Early pancreatic endoderm differentiated similarly from STAT3(K392R) and healthy-control cells, but in later stages, NEUROG3 expressionwas upregulated prematurely in STAT3(K392R) cells together with insulin (INS) and glucagon (GCG). RNA sequencing (RNA-seq) showed robust NEUROG3 downstream targets upregulation. STAT3 mutation correction with CRISPR/Cas9 reversed completely the disease phenotype. STAT3(K392R) -activating properties were not explained fully by altered DNA-binding affinity or increased phosphorylation. Instead, reporter assays demonstrated NEUROG3 promoter activation by STAT3 in pancreatic cells. Furthermore, proteomic and immunocytochemical analyses revealed increased nuclear translocation of STAT3(K392R). Collectively, our results demonstrate that the STAT3(K392R) mutation causes premature endocrine differentiation through direct induction of NEUROG3 expression.

The recent discovery that genetically modified α cells can regenerate and convert into β-like cells in vivo holds great promise for diabetes research. However, to eventually translate these findings to human, it is crucial to discover compounds with similar activities. Herein, we report the identification of GABA as an inducer of α-to-β-like cell conversion in vivo. This conversion induces α cell replacement mechanisms through the mobilization of duct-lining precursor cells that adopt an α cell identity prior to being converted into β-like cells, solely upon sustained GABA exposure. Importantly, these neo-generated β-like cells are functional and can repeatedly reverse chemically induced diabetes in vivo. Similarly, the treatment of transplanted human islets with GABA results in a loss of α cells and a concomitant increase in β-like cell counts, suggestive of α-to-β-like cell conversion processes also in humans. This newly discovered GABA-induced α cell-mediated β-like cell neogenesis could therefore represent an unprecedented hope toward improved therapies for diabetes., SCOPUS: ar.j, info:eu-repo/semantics/published

AIMS/HYPOTHESIS: Type 2 diabetes is a bi-hormonal disease characterised by relative hypoinsulinaemia and hyperglucagonaemia with elevated blood glucose levels. Besides pancreatic beta cell defects, a low number of beta cells (low beta cell mass) may contribute to the insufficient secretion of insulin. In this study our aim was to determine whether the alpha cell mass is also altered. METHODS: Using a point counting method, we measured the ratio of alpha to beta cell areas in pancreas samples obtained at autopsy from 50 type 2 diabetic subjects, whose beta cell mass had previously been found to be 36% lower than that of 52 non-diabetic subjects. RESULTS: The topography of alpha and beta cells was similar in both groups: many alpha cells were localised in the centre of the islets and the ratio of alpha/beta cell areas increased with islet size. The average ratio was significantly higher in type 2 diabetic subjects (0.72) than in non-diabetic subjects (0.42), with, however, a large overlap between the two groups. In contrast, the alpha cell mass was virtually identical in type 2 diabetic subjects (366 mg) and non-diabetic subjects (342 mg), and was not influenced by sex, BMI or type of diabetes treatment. CONCLUSIONS: The higher proportion of alpha to beta cells in the islets of some type 2 diabetic subjects is due to a decrease in beta cell number rather than an increase in alpha cell number. This imbalance may contribute to alterations in the normal inhibitory influence exerted by beta cells on alpha cells, and lead to the relative hyperglucagonaemia observed in type 2 diabetes

BACKGROUND: Chromogranin (Cg) A is expressed in neuroendocrine and neuronal tissues. It is involved in the generation of secretory granules and is cleaved to form biologically active peptides. Targeted ablation of the Chga gene resulted in increased plasma catecholamines, high blood pressure, and decreased size and number of adrenal medullary chromaffin granules. The aim of this study was to determine whether Chga null mice display changes in the morphology and function of the endocrine pancreas. MATERIALS AND METHODS: Sections of pancreata from Chga-/-, Chga+/- and Chga+/+ mice, were immunostained with antibodies against synaptophysin, CgA, CgB, secretogranin II and the four major pancreatic islet hormones. Plasma was analysed for glucose, insulin, glucagon, somatostatin and pancreatic polypeptide (PP). RESULTS: CgA epitopes were undetectable in the islets of Chga-/- animals. CgB and secretogranin II epitopes were expressed in the islets of all animal groups albeit with decreased expression in Chga-/- islets. The islet number and size were decreased in the Chga-/- animals compared with Chga+/+. The proportion of insulin cells was decreased but somatostatin and PP cells were increased in Chga-/- mice compared to Chga+/+ mice. The nuclear size was decreased in insulin cells and increased in somatostatin cells in Chga-/- mice. Plasma insulin level was markedly decreased in the Chga-/- mice although fasting plasma glucose and glucagon were normal. CONCLUSION: Ablation of the Chga gene affected the islet volume, the composition, distribution and nuclear size of islet cell types and plasma insulin concentration. Our data indicate decreased insulin cell function and increased glucagon cell function. Our study shows that CgA exerts a significant influence on the endocrine pancreas with importance in maintaining islet volume, cellular composition and function.

Poor growth before birth increases the risk of non-insulin-dependent diabetes mellitus (NIDDM) and impairs insulin secretion relative to sensitivity. We investigated the effects of intrauterine growth restriction in sheep on insulin secretion, beta-cell mass, and function from before birth to young adulthood and its molecular basis. Pancreas was collected from control and placentally restricted sheep as fetuses (d 143 gestation), lambs (aged 42 d), and young adults (aged 556 d), following independent measures of in vivo insulin secretion and sensitivity. beta-Cells and islets were counted after immunohistochemical staining for insulin. In lambs, gene expression was measured by RT-PCR and expressed relative to 18S. beta-Cell mass correlated positively with fetal weight but negatively with birth weight in adult males. Glucose-stimulated insulin disposition and beta-cell function correlated negatively with fetal weight but positively with birth weight in adult males. Placental restriction increased pancreatic expression of IGF-II and IGF-I but decreased that of voltage-gated calcium channel, alpha1D subunit (CACNA1D) in lambs. In male lambs, pancreatic IGF-II and insulin receptor expression correlated strongly and positively with beta-cell mass and CACNA1D expression with glucose-stimulated insulin disposition. Restricted growth before birth in the sheep does not impair insulin secretion, relative to sensitivity, before birth or in young offspring. IGF-II and insulin receptor are implicated as key molecular regulators of beta-cell mass compensation, whereas impaired expression of the voltage-gated calcium channel may underlie impaired beta-cell function after intrauterine growth restriction. With aging, the insulin secretory capacity of the beta-cell is impaired in males, and their increases in beta-cell mass are inadequate to maintain adequate insulin secretion relative to sensitivity.

OBJECTIVE—Clinical islet transplantations are performed through infusion of islets via the portal vein into the liver. This study aimed at characterizing the influence of the implantation microenvironment on islet graft metabolism and function. RESEARCH DESIGN AND METHODS—Islets were transplanted into their normal environment, i.e., the pancreas, or intraportally into the liver of mice. One month posttransplantation, the transplanted islets were retrieved and investigated for changes in function and gene expression. RESULTS—Insulin content, glucose-stimulated insulin release, (pro)insulin biosynthesis, and glucose oxidation rate were markedly decreased in islets retrieved from the liver, both when compared with islets transplanted into the pancreas and endogenous islets. Islets transplanted into the pancreas showed normal insulin content, (pro)insulin biosynthesis, and glucose oxidation rate but increased basal insulin secretion and impaired glucose stimulation index. Gene expression data for retrieved islets showed downregulation of pancreatic and duodenal homeobox gene-1, GLUT-2, glucokinase, mitochondrial glycerol-phosphate dehydrogenase, and pyruvate carboxylase, preferentially in intraportally transplanted islets. CONCLUSIONS—Islets transplanted into their normal microenvironment, i.e., the pancreas, display gene expression changes when compared with endogenous islets but only moderate changes in metabolic functions. In contrast, site-specific properties of the liver markedly impaired the metabolic functions of intraportally transplanted islets.

[Persistent hyperinsulinemic hypoglycemia of infancy: the pathologist's experience]. Persistent hyperinsulinemic hypoglycemia of Infancy (PHHI) is characterized by episodes of severe hypoglycemia exposing the child to serious neurological sequelae. The morphologic pancreatic anomalies observed consist in either a focal lesion which can be totally cured by a selective surgical resection, or a diffuse and poorly understood lesion of pancreatic tissue, which may appear at first glance to be both macroscopically and microscopically normal, the treatment of which, requires a near-total pancreatectomy. The studies presented concentrate on several pathogenic hypotheses of this latter form of PHHI. We first demonstrate that nesidioblastosis, long considered as the original lesion for the diffuse form of hyperinsulinism, does indeed exist although it is not specific to this disease and does not correspond to a permanent proliferation of endocrine cells. We then dismiss the hypothesis of an enhanced B cell mass, as the volume density of B cells is not systematically increased in hyperinsulinemic children compared to controls. The third hypothesis looking to a decreased D cell mass has to be approached with circumspection as the difference in volume density of somatostatin cells, which tends to be slightly lower in hypoglycemic children, is small and inconsistent. The fourth hypothesis concerns an intrinsic functional lesion of the B cells, and is supported by an increased quantity of proinsulin detected in the Golgi area as well as by the observation of voluminous nuclei and a particularly abundant cytoplasm in certain B cells. These histological anomalies are detected on per-operative frozen sections and guide the surgical treatment.

Persistent hyperinsulinemic hypoglycemia of Infancy (PHHI) is characterized by episodes. of severe hypoglycemia exposing the child to serious neurological sequelae. The morphologic pancreatic anomalies observed consist in either a focal lesion which can be totally cured by a selective surgical resection, or a diffuse and poorly understood lesion of pancreatic tissue, which may appear at first glance to be both macroscopically and microscopically normal, the treatment of which, requires a near-total pancreatectomy. The studies presented concentrate on several pathogenic hypotheses of this latter form of PHHI. We first demonstrate that nesidioblastosis, long considered as the original lesion for the diffuse form of hyperinsulinism, does indeed exist although it is not specific to this disease and does not correspond to a permanent proliferation of endocrine cells. We then dismiss the hypothesis of an enhanced B cell moss, as the, volume density of 8 cells is not systematically increased in hyperinsulinemic children compared to controls. The third hypothesis looking to a decreased D cell moss has to be approached with circumspection as the difference in volume density of somatostatin cells, which tends to be slightly lower in hypoglycemic children, is small and inconsistent. The fourth hypothesis concerns an intrinsic functional lesion of the 8 cells, and is supported by on Increased quantity of proinsulin detected in the Golgi area as well as by the observation of voluminous nuclei and a particularly abundant cytoplasm in certain B cells. These histological anomalies ore detected on per-operative frozen sections and guide the surgical treatment.

info:eu-repo/semantics/published

info:eu-repo/semantics/published

The ontogeny of the endocrine pancreas of a teleost, the turbot (Scophthalmus maximus), was investigated by the use of double immunofluorescence. Clustered insulin (INS)-immunoreactive (IR) cells were observed on the first day after hatching. During the following days, the islet largely increased in size and some smaller islets appeared. All islets consisted only of INS-IR cells. Between day 5 (onset of exogenous feeding) and 7, somatostatin (SOM) and glucagon (GLUC) cells appeared. In the large (principal) islet, the SOM-IR cells intermingled with the INS-IR cells. In the secondary islets, they occurred at the periphery. The GLUC-IR cells were located at the periphery in all islets. Subsequently, two-four additional small principal islets appeared. At day 11, pancreatic polypeptide (PP)-IR cells were present in principal islets and secondary islets. Starting with day 11, in all islets, insulin-like growth factor 1 (IGF-1) immunoreactivity was localized in numerous PP-IR cells and GLUC-IR and some SOM-IR cells. It also occurred in enteroendocrine cells that seemed to contain none of the classical islet hormones. The early appearance of INS correlates with its key role in the regulation of fish protein and lipid metabolism. Islet-derived IGF-1 might inhibit the regulation of INS secretion in a paracrine manner and may be highly involved in growth-promoting processes.

SCOPUS: ar.j, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published