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Aim: To evaluate sex differences in gastric emptying and the glycaemic response to a glucose drink and a high carbohydrate meal in type 2 diabetes (T2D). Methods: In cohort 1, 70 newly diagnosed, treatment‐naïve Chinese patients with T2D (44 men) recruited from a diabetes outpatient clinic ingested a 75‐g glucose drink containing 150 mg 13C‐acetate. In cohort 2, 101 Australian patients with T2D (67 male) recruited from the community, managed by diet and/or metformin monotherapy, ingested a semi‐solid mashed potato meal, labelled with 100 μl 13C‐octanoic acid. Breath samples were collected over 3 and 4 h, respectively, for assessment of gastric emptying, and venous blood was sampled for evaluation of glycaemia (with and without adjustment for each participant's estimated total blood volume). Results: Gastric emptying was slower in female than male subjects in both cohorts (both p <.01). Multiple linear regression analyses revealed that gastric emptying was independently associated with sex (both p <.05). Without adjustment for blood volume, the glycaemic responses to oral glucose and the mixed meal were greater in female subjects (both p <.001). However, after adjustment for blood volume, the glycaemic responses were greater in men (both p <.05). Conclusions: Gastric emptying is slower in women than men with T2D, associated with a reduced blood volume‐adjusted glycaemic response to oral glucose and a mixed meal in women. These observations highlight the sex difference in postprandial glucose handling, which is relevant to the personalized management of postprandial glycaemia in T2D. [ABSTRACT FROM AUTHOR]

Aim: To evaluate gastric emptying (GE) and the glycaemic response to a 75‐g oral glucose load in newly diagnosed, treatment‐naïve Han Chinese with type 2 diabetes (T2D) before insulin pump therapy, after 4 weeks of insulin pump therapy, and 12–15 months after insulin pump therapy. Materials and Methods: Twenty participants with T2D (baseline glycated haemoglobin [± SD] 10.7% [± 1.2%] 93 [± 10] mmol/mol) ingested a 75‐g glucose drink containing 150 mg 13C‐acetate, to determine the gastric half‐emptying time, and underwent assessment of plasma glucose and serum insulin, C‐peptide and glucagon‐like peptide‐1 (GLP‐1) over 180 min before and after 4 weeks of insulin pump therapy (discontinued for 48 h before re‐assessment). Data were compared to those in 19 healthy participants matched for sex and age. After 12–15 months, GE was re‐measured in 14 of the T2D participants. Results: At baseline, participants with T2D exhibited substantially augmented fasting and post‐glucose glycaemia, diminished insulin secretion, and more rapid GE (p < 0.05 each), but comparable GLP‐1, compared to healthy participants. Following insulin pump therapy, insulin secretion increased, GLP‐1 secretion was attenuated, fasting and post‐glucose glycaemia were lower, and GE was slowed (p < 0.05 each). The slowing of GE in T2D participants was sustained over 12–15 months of follow‐up. Conclusions: In newly diagnosed Han Chinese with T2D, GE is often accelerated despite poor glycaemic control and is slowed by short‐term insulin pump therapy. The effect on GE is maintained for at least 12 months. [ABSTRACT FROM AUTHOR]

To achieve accurate deformation prediction and assess the temporal stability of surrounding rock in underground mines, this study utilizes the G-P algorithm to determine the optimal embedding dimension and time delay for the reconstructed phase space of the deformation time series. Analyzing the dynamic evolution of the nearest phase point and employing grey prediction theory in the phase space reconstruction, we predict the time series of surrounding rock deformation. Results indicate that the optimal embedding dimension and time delay for the deformation time series are 3. The larger the average distance of the nearest phase point, the more pronounced the chaotic characteristics of perimeter rock deformation, signifying a complex intrinsic dynamical system. The grey theory proves effective in short-term, accurate deformation prediction for perimeter rock. Additionally, the identified stability of perimeter rock based on neighboring phase points and deformation prediction results offers a novel approach for evaluating surrounding rock stability in underground mining processes. [ABSTRACT FROM AUTHOR]

Busulfan is a bifunctional alkylating agent that is widely used before hematopoietic stem cell transplantation (HSCT), in combination with other chemotherapeutic drugs. As of 2020, there is no population pharmacokinetic (popPK) model for busulfan in Chinese pediatric patients. A systemic external evaluation of 11 published popPK models was conducted in Chinese pediatric patients undergoing HSCT. Forty pediatric patients were enrolled in this study, with a total of 183 blood concentrations. The relative prediction error (PE%), median PE%, median absolute PE%, and percentage of PE% within ±20% and ±30% were calculated in prediction‐based diagnostics. Simulation‐based diagnostics were conducted through a prediction‐ and variability‐corrected visual predictive check and the normalized prediction distribution error. The relative individual prediction error was calculated using Bayesian forecasting with 1 to 3 concentration points. The 1‐compartment open linear popPK model, which was built by Su‐jin Rhee et al (model H), incorporating the patient's body surface area, age, dosing day, and aspartate aminotransferase as significant covariates had preferable predictability than other popPK models. In prediction‐based diagnostics, the median PE%, percentage of PE% within ±20%, and percentage of PE% within ±30% of model H were 8.48%, 45.35%, and 59.56%, respectively. The normalized prediction distribution error of model H showed that it followed the normal distribution. Based on Bayesian forecasting, model H showed good predictive performance. Thus, model H was the most appropriate model that can be used clinically for individualized dosage adjustments in Chinese pediatric HSCT patients. [ABSTRACT FROM AUTHOR]

Context: Both gastric emptying and the secretion of glucagon-like peptide-1 (GLP-1) are major determinants of postprandial glycemia in health and type 2 diabetes (T2D). GLP-1 secretion after a meal is dependent on the entry of nutrients into the small intestine, which, in turn, slows gastric emptying. Objective: To define the relationship between gastric emptying and the GLP-1 response to both oral and small intestinal nutrients in subjects with and without T2D. Methods: We evaluated: (i) the relationship between gastric emptying (breath test) and postprandial GLP-1 levels after a mashed potato meal in 73 individuals with T2D; (ii) interindividual variations in GLP-1 response to (a) intraduodenal glucose (4 kcal/min) during euglycemia and hyperglycemia in 11 healthy and 12 T2D, subjects, (b) intraduodenal fat (2 kcal/min) in 15 T2D subjects, and (c) intraduodenal protein (3 kcal/min) in 10 healthy subjects; and (iii) the relationship between gastric emptying (breath test) of 75 g oral glucose and the GLP-1 response to intraduodenal glucose (4 kcal/min) in 21 subjects (9 healthy, 12 T2D). Results: The GLP-1 response to the mashed potato meal was unrelated to the gastric half-emptying time (T50). The GLP-1 responses to intraduodenal glucose, fat, and protein varied substantially between individuals, but intra-individual variation to glucose was modest. The T50 of oral glucose was related directly to the GLP-1 response to intraduodenal glucose (r = 0.65, P = 0.002). Conclusion: In a given individual, gastric emptying is not a determinant of the postprandial GLP-1 response. However, the intrinsic gastric emptying rate is determined in part by the responsiveness of GLP-1 to intestinal nutrients. [ABSTRACT FROM AUTHOR]

Calcium ions (Ca2+) take part in intra‐ and inter‐cellular signaling to mediate cellular functions. Sensing this ubiquitous messenger is instrumental in disentangling the specific functions of cellular sub‐compartments and/or intercellular communications. In this review, the authors first describe intra‐ and inter‐cellular Ca2+ signaling in relation to insulin secretion from the pancreatic islets, and then outline the development of diverse sensors, for example, chemically synthesized indicators, genetically encoded proteins, and ion‐selective microelectrodes, for intra‐ and extra‐cellular sensing of Ca2+. Particular emphasis is placed on emerging approaches in this field, such as low‐affinity Ca2+ indicators and unique Ca2+‐responsive composite materials. The authors conclude by remarking on the challenges and opportunities for further developments in this field, which may facilitate a more comprehensive understanding of Ca2+ signaling within and outside the islets, and its relevance in health and disease. [ABSTRACT FROM AUTHOR]

There is increasing evidence linking bitter taste receptor (BTR) signaling to gut hormone secretion and glucose homeostasis. However, its effect on islet hormone secretion has been poorly characterized. This study investigated the effect of the bitter substance, denatonium benzoate (DB), on hormone secretion from mouse pancreatic islets and INS-1 832/13 cells. DB (0.5-1 mM) augmented insulin secretion at both 2.8 mM and 16.7 mM glucose. This effect was no longer present at 5 mM DB likely due to the greater levels of cellular apoptosis. DB-stimulated insulin secretion involved closure of the K ATP channel, activation of T2R signaling in beta-cells, and intraislet glucagon-like peptide-1 (GLP-1) release. DB also enhanced glucagon and somatostatin secretion, but the underlying mechanism was less clear. Together, this study demonstrates that the bitter substance, DB, is a strong potentiator of islet hormone secretion independent of glucose. This observation highlights the potential for widespread off-target effects associated with the clinical use of bitter-tasting substances. NEW & NOTEWORTHY We show that the bitter substance, denatonium benzoate (DB), stimulates insulin, glucagon, somatostatin, and GLP-1 secretion from pancreatic islets, independent of glucose, and that DB augments insulin release via the K ATP channel, bitter taste receptor signaling, and intraislet GLP-1 secretion. Exposure to a high dose of DB (5 mM) induces cellular apoptosis in pancreatic islets. Therefore, clinical use of bitter substances to improve glucose homeostasis may have unintended negative impacts beyond the gut.

Extracellular Ca 2+ ([Ca 2+ ] ex ) is an important regulator of various physiological and pathological functions, including intercellular communication for synchronized cellular activities (e.g., coordinated hormone secretion from endocrine tissues). Yet it is rarely possible to concurrently quantify the dynamic changes of [Ca 2+ ] ex and related bioactive molecules with high accuracy and temporal resolution. This work aims to develop a multiplexed microfluidic platform to enable monitoring oscillatory [Ca 2+ ] ex and hormone(s) in a biomimetic environment. To this end, a low-affinity fluorescent indicator, Rhod-5N, is identified as a suitable sensor for a range of [Ca 2+ ] ex based on its demonstrated high sensitivity and selectivity to Ca 2+ in biomedical samples, including human serum and cell culture medium. A microfluidic chip is devised to allow for the immobilization of microscale subjects (analogous to biological tissues), precise control of the perfusion gradient at sites of interest, and integration of modalities for fluorescence measurement and enzyme-linked immunosorbent assay. As this analytical system is demonstrated to be viable to quantify the dynamic changes of Ca 2+ (0.2-2 mM) and insulin (15-150 mU L -1 ) concurrently, with high temporal resolution, it has the potential to provide key insights into the essential roles of [Ca 2+ ] ex in the secretory function of endocrine tissues and to identify novel therapeutic targets for human diseases.