scholarly journals Microfluidic device integrating a network of hyper-elastic valves for automated glucose stimulation and insulin secretion collection from a single pancreatic islet

2021 ◽  
Author(s):  
Clement Quintard ◽  
Emily Tubbs ◽  
Jean-Luc Achard ◽  
Fabrice Navarro ◽  
Xavier Gidrol ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Large Scale ◽  
Biological Tissues ◽  
Microfluidic Platforms ◽  
User Friendliness ◽  
Glucose Stimulation ◽  
Automated Control ◽  
Microphysiological Systems ◽  
Hyper Elastic

Advances in microphysiological systems have prompted the need for robust and reliable cell culture devices. While microfluidic technology has made significant progress, devices often lack user-friendliness and are not designed to be industrialized on a large scale. Pancreatic islets are often being studied using microfluidic platforms in which the monitoring of fluxes is generally very limited, especially because the integration of valves to direct the flow is difficult to achieve. Considering these constraints, we present a thermoplastic manufactured microfluidic chip with an automated control of fluxes for the stimulation and secretion collection of pancreatic islet. The islet was directed toward precise locations through passive hydrodynamic trapping and both dynamic glucose stimulation and insulin harvesting were done automatically via a network of large deformation valves, directing the reagents and the pancreatic islet toward different pathways. This device we developed enables monitoring of insulin secretion from a single islet and can be adapted for the study of a wide variety of biological tissues and secretomes.

scholarly journals Dapagliflozin Does Not Directly Affect Human α or β Cells

Endocrinology ◽  
2020 ◽  
Vol 161 (8) ◽  
Author(s):  
Chunhua Dai ◽  
John T Walker ◽  
Alena Shostak ◽  
Yasir Bouchi ◽  
Greg Poffenberger ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Human Insulin ◽  
Pancreatic Islet ◽  
Glucagon Secretion ◽  
Human Islets ◽  
Glucose Stimulation ◽  
Lower Blood Glucose ◽  
Lower Blood

Abstract Selective inhibitors of sodium glucose cotransporter-2 (SGLT2) are widely used for the treatment of type 2 diabetes and act primarily to lower blood glucose by preventing glucose reabsorption in the kidney. However, it is controversial whether these agents also act on the pancreatic islet, specifically the α cell, to increase glucagon secretion. To determine the effects of SGLT2 on human islets, we analyzed SGLT2 expression and hormone secretion by human islets treated with the SGLT2 inhibitor dapagliflozin (DAPA) in vitro and in vivo. Compared to the human kidney, SLC5A2 transcript expression was 1600-fold lower in human islets and SGLT2 protein was not detected. In vitro, DAPA treatment had no effect on glucagon or insulin secretion by human islets at either high or low glucose concentrations. In mice bearing transplanted human islets, 1 and 4 weeks of DAPA treatment did not alter fasting blood glucose, human insulin, and total glucagon levels. Upon glucose stimulation, DAPA treatment led to lower blood glucose levels and proportionally lower human insulin levels, irrespective of treatment duration. In contrast, after glucose stimulation, total glucagon was increased after 1 week of DAPA treatment but normalized after 4 weeks of treatment. Furthermore, the human islet grafts showed no effects of DAPA treatment on hormone content, endocrine cell proliferation or apoptosis, or amyloid deposition. These data indicate that DAPA does not directly affect the human pancreatic islet, but rather suggest an indirect effect where lower blood glucose leads to reduced insulin secretion and a transient increase in glucagon secretion.

Synchronized Microfluidic System to Dynamically Assess Pancreatic Islet Function beyond Glucose-Stimulated Insulin Secretion

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2162-P
Author(s):  
STEPHAN NIEUWOUDT ◽  
RUTH MCDOWELL ◽  
HUI ZHANG ◽  
JOHN P. KIRWAN
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Microfluidic System ◽  
Islet Function ◽  
Glucose Stimulated Insulin Secretion

scholarly journals GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonathan Snyder ◽  
Atreju I Lackey ◽  
G. Schuyler Brown ◽  
Melisa Diaz ◽  
Tian Yuzhen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Cell Model ◽  
Metabolic Phenotype ◽  
Atp Production ◽  
Pancreatic Islets Of Langerhans ◽  
Cardiac Mitochondrion ◽  
Pre Treatment ◽  
Insulin Responses

AbstractDiabetes is a metabolic syndrome rooted in impaired insulin and/or glucagon secretory responses within the pancreatic islets of Langerhans (islets). Insulin secretion is primarily regulated by two key factors: glucose-mediated ATP production and G-protein coupled receptors (GPCRs) signaling. GPCR kinase 2 (GRK2), a key regulator of GPCRs, is reported to be downregulated in the pancreas of spontaneously obesogenic and diabetogenic mice (ob/ob). Moreover, recent studies have shown that GRK2 non-canonically localizes to the cardiac mitochondrion, where it can contribute to glucose metabolism. Thus, islet GRK2 may impact insulin secretion through either mechanism. Utilizing Min6 cells, a pancreatic ß-cell model, we knocked down GRK2 and measured glucose-mediated intracellular calcium responses and insulin secretion. Silencing of GRK2 attenuated calcium responses, which were rescued by pertussis toxin pre-treatment, suggesting a Gαi/o-dependent mechanism. Pancreatic deletion of GRK2 in mice resulted in glucose intolerance with diminished insulin secretion. These differences were due to diminished insulin release rather than decreased insulin content or gross differences in islet architecture. Furthermore, a high fat diet feeding regimen exacerbated the metabolic phenotype in this model. These results suggest a new role for pancreatic islet GRK2 in glucose-mediated insulin responses that is relevant to type 2 diabetes disease progression.

scholarly journals Improved in vivo imaging method for individual islets across the mouse pancreas reveals a heterogeneous insulin secretion response to glucose

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Henriette Frikke-Schmidt ◽  
Peter Arvan ◽  
Randy J. Seeley ◽  
Corentin Cras-Méneur
Keyword(s):  
Insulin Secretion ◽  
In Vivo Imaging ◽  
Motion Blur ◽  
Isolated Islets ◽  
Imaging Method ◽  
Glucose Stimulation ◽  
Powerful Approach ◽  
Glucose Challenge ◽  
The Impact

AbstractWhile numerous techniques can be used to measure and analyze insulin secretion in isolated islets in culture, assessments of insulin secretion in vivo are typically indirect and only semiquantitative. The CpepSfGFP reporter mouse line allows the in vivo imaging of insulin secretion from individual islets after a glucose stimulation, in live, anesthetized mice. Imaging the whole pancreas at high resolution in live mice to track the response of each individual islet over time includes numerous technical challenges and previous reports were only limited in scope and non-quantitative. Elaborating on this previous model—through the development of an improved methodology addressing anesthesia, temperature control and motion blur—we were able to track and quantify longitudinally insulin content throughout a glucose challenge in up to two hundred individual islets simultaneously. Through this approach we demonstrate quantitatively for the first time that while isolated islets respond homogeneously to glucose in culture, their profiles differ significantly in vivo. Independent of size or location, some islets respond sharply to a glucose stimulation while others barely secrete at all. This platform therefore provides a powerful approach to study the impact of disease, diet, surgery or pharmacological treatments on insulin secretion in the intact pancreas in vivo.

scholarly journals PWD/PhJ and WSB/EiJ Mice Are Resistant to Diet-Induced Obesity But Have Abnormal Insulin Secretion

Endocrinology ◽  
2011 ◽  
Vol 152 (8) ◽  
pp. 3005-3017 ◽  
Author(s):  
Katie T. Y. Lee ◽  
Subashini Karunakaran ◽  
Maggie M. Ho ◽  
Susanne M. Clee
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Large Scale ◽  
Mouse Strains ◽  
Second Phase ◽  
Fasting Insulin ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes

Recently, novel inbred mouse strains that are genetically distinct from the commonly used models have been developed from wild-caught mice. These wild-derived inbred strains have been included in many of the large-scale genomic projects, but their potential as models of altered obesity and diabetes susceptibility has not been assessed. We examined obesity and diabetes-related traits in response to high-fat feeding in two of these strains, PWD/PhJ (PWD) and WSB/EiJ (WSB), in comparison with C57BL/6J (B6). Young PWD mice displayed high fasting insulin levels, although they had normal insulin sensitivity. PWD mice subsequently developed a much milder and delayed-onset obesity compared with B6 mice but became as insulin resistant. PWD mice had a robust first-phase and increased second-phase glucose-stimulated insulin secretion in vivo, rendering them more glucose tolerant. WSB mice were remarkably resistant to diet-induced obesity and maintained very low fasting insulin throughout the study. WSB mice exhibited more rapid glucose clearance in response to an insulin challenge compared with B6 mice, consistent with their low percent body fat. Interestingly, in the absence of a measurable in vivo insulin secretion, glucose tolerance of WSB mice was better than B6 mice, likely due to their enhanced insulin sensitivity. Thus PWD and WSB are two obesity-resistant strains with unique insulin secretion phenotypes. PWD mice are an interesting model that dissociates hyperinsulinemia from obesity and insulin resistance, whereas WSB mice are a model of extraordinary resistance to a high-fat diet.

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