CRFR1 and CRFR2 Receptors Are Expressed in Pancreatic Islets, Promote Beta Cell Proliferation and Potentiate Insulin Secretion in a Glucose-Dependent Manner.

2010 ◽  
pp. OR32-6-OR32-6
Author(s):  
MO Huising ◽  
T van der Meulen ◽  
AP Pilbrow ◽  
M Matsumoto ◽  
JM Vaughan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Beta Cell Proliferation ◽  
Dependent Manner

scholarly journals Vitamin B6 deficiency disrupts serotonin signaling in pancreatic islets and induces gestational diabetes in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ashley M. Fields ◽  
Kevin Welle ◽  
Elaine S. Ho ◽  
Clementina Mesaros ◽  
Martha Susiarjo
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Glucose Intolerance ◽  
Vitamin B6 ◽  
Serotonin Receptor ◽  
Dependent Manner ◽  
Β Cell ◽  
Vitamin B6 Deficiency ◽  
Maternal Glucose

AbstractIn pancreatic islets, catabolism of tryptophan into serotonin and serotonin receptor 2B (HTR2B) activation is crucial for β-cell proliferation and maternal glucose regulation during pregnancy. Factors that reduce serotonin synthesis and perturb HTR2B signaling are associated with decreased β-cell number, impaired insulin secretion, and gestational glucose intolerance in mice. Albeit the tryptophan-serotonin pathway is dependent on vitamin B6 bioavailability, how vitamin B6 deficiency impacts β-cell proliferation during pregnancy has not been investigated. In this study, we created a vitamin B6 deficient mouse model and investigated how gestational deficiency influences maternal glucose tolerance. Our studies show that gestational vitamin B6 deficiency decreases serotonin levels in maternal pancreatic islets and reduces β-cell proliferation in an HTR2B-dependent manner. These changes were associated with glucose intolerance and insulin resistance, however insulin secretion remained intact. Our findings suggest that vitamin B6 deficiency-induced gestational glucose intolerance involves additional mechanisms that are complex and insulin independent.

scholarly journals High-throughput analysis of ANRIL circRNA isoforms in human pancreatic islets

2022 ◽  
Author(s):  
Hannah J MacMillan ◽  
Yahui Kong ◽  
Ezequiel Calvo-Roitberg ◽  
Laura C Alonso ◽  
Athma A Pai
Keyword(s):  
Cell Proliferation ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Molecular Mechanisms ◽  
Circular Rna ◽  
Beta Cell Proliferation ◽  
High Throughput Analysis ◽  
Exon 2 ◽  
Human Pancreatic Islets ◽  
Protective Allele

The antisense non-coding RNA in the INK locus (ANRIL) is a hotspot for genetic variants associated with cardiometabolic disease. We recently found increased ANRIL abundance in human pancreatic islets from donors with certain Type II Diabetes (T2D) risk-SNPs, including a T2D risk-SNP located within ANRIL exon 2 associated with beta cell proliferation. Recent studies have found that expression of circular species of ANRIL is linked to the regulation of cardiovascular phenotypes. Less is known about how the abundance of circular ANRIL may influence T2D phenotypes. Herein, we sequence circular RNA in pancreatic islets to characterize circular isoforms of ANRIL. We identify highly expressed circular ANRIL isoforms whose expression is correlated across dozens of individuals and characterize ANRIL splice sites that are commonly involved in back-splicing. We find that samples with the T2D risk allele in ANRIL exon 2 had higher ratios of circular to linear ANRIL compared to protective-allele carriers, and that higher circular:linear ANRIL was associated with decreased beta cell proliferation. Our study points to a combined involvement of both linear and circular ANRIL species in T2D phenotypes and opens the door for future studies of the molecular mechanisms by which ANRIL impacts cellular function in pancreatic islets.

scholarly journals AAV8-mediated gene transfer of microRNA-132 improves beta cell function in mice fed a high-fat diet

2019 ◽  
Vol 240 (2) ◽  
pp. 123-132 ◽  
Author(s):  
Niels L Mulder ◽  
Rick Havinga ◽  
Joost Kluiver ◽  
Albert K Groen ◽  
Janine K Kruit
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
Gene Transfer ◽  
Beta Cell ◽  
Beta Cells ◽  
High Fat Diet ◽  
Beta Cell Function ◽  
Cell Function ◽  
Beta Cell Proliferation ◽  
High Fat

MicroRNAs have emerged as essential regulators of beta cell function and beta cell proliferation. One of these microRNAs, miR-132, is highly induced in several obesity models and increased expression of miR-132 in vitro modulates glucose-stimulated insulin secretion. The aim of this study was to investigate the therapeutic benefits of miR-132 overexpression on beta cell function in vivo. To overexpress miR-132 specifically in beta cells, we employed adeno-associated virus (AAV8)-mediated gene transfer using the rat insulin promoter in a double-stranded, self-complementary AAV vector to overexpress miR-132. Treatment of mice with dsAAV8-RIP-mir132 increased miR-132 expression in beta cells without impacting expression of miR-212 or miR-375. Surprisingly, overexpression of miR-132 did not impact glucose homeostasis in chow-fed animals. Overexpression of miR-132 did improve insulin secretion and hence glucose homeostasis in high-fat diet-fed mice. Furthermore, miR-132 overexpression increased beta cell proliferation in mice fed a high-fat diet. In conclusion, our data show that AAV8-mediated gene transfer of miR-132 to beta cells improves beta cell function in mice in response to a high-fat diet. This suggests that increased miR-132 expression is beneficial for beta cell function during hyperglycemia and obesity.

scholarly journals Neural crest stem cells increase beta cell proliferation and improve islet function in co-transplanted murine pancreatic islets

Diabetologia ◽  
2009 ◽  
Vol 52 (12) ◽  
pp. 2594-2601 ◽  
Author(s):  
J. Olerud ◽  
N. Kanaykina ◽  
S. Vasilovska ◽  
D. King ◽  
M. Sandberg ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Beta Cell ◽  
Neural Crest ◽  
Pancreatic Islets ◽  
Beta Cell Proliferation ◽  
Islet Function ◽  
Neural Crest Stem Cells

scholarly journals Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Hossein Rahavi ◽  
Seyed Mahmoud Hashemi ◽  
Masoud Soleimani ◽  
Jamal Mohammadi ◽  
Nader Tajik
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Dependent Manner ◽  
Diabetic Mice ◽  
Mice Model

Regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) might be applied for type 1 diabetes mellitus (T1DM) treatment. Thus, we proposed in vitro assessment of adipose tissue-derived MSCs (AT-MSCs) immunomodulation on autoimmune response along with beta cell protection in streptozotocin- (STZ-) induced diabetic C57BL/6 mice model. MSCs were extracted from abdominal adipose tissue of normal mice and cultured to proliferate. Diabetic mice were prepared by administration of multiple low-doses of streptozotocin. Pancreatic islets were isolated from normal mice and splenocytes prepared from normal and diabetic mice. Proliferation, cytokine production, and insulin secretion assays were performed in coculture experiments. AT-MSCs inhibited splenocytes proliferative response to specific (islet lysate) and nonspecific (PHA) triggers in a dose-dependent manner (P<0.05). Decreased production of proinflammatory cytokines, such as IFN-γ, IL-2, and IL-17, and increased secretion of regulatory cytokines such as TGF-β, IL-4, IL-10, and IL-13 by stimulated splenocytes were also shown in response to islet lysate or PHA stimulants (P<0.05). Finally, we demonstrated that AT-MSCs could effectively sustain viability as well as insulin secretion potential of pancreatic islets in the presence of reactive splenocytes (P<0.05). In conclusion, it seems that MSCs may provide a new horizon for T1DM cell therapy and islet transplantation in the future.

Effect of glucose on beta cell proliferation and population size in organ culture of foetal and neonatal rat pancreases

Development ◽  
1983 ◽  
Vol 75 (1) ◽  
pp. 303-312
Author(s):  
Hue-Lee Cheng Kaung
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
Organ Culture ◽  
Beta Cell ◽  
Population Size ◽  
Cell Population ◽  
Beta Cell Proliferation ◽  
Glucose Stimulation ◽  
Foetal Tissue ◽  
Effect Of Glucose

The effect of glucose on growth of the beta cell population was characterized in rat pancreatic organ culture. The effect was monitored by measuring [3H]thymidine labelling indices of beta cells during the culture period and by quantitation of beta cell population size at the end of the culture period. Foetal and neonatal pancreases and different glucose levels were compared. Glucose was found to be effective in stimulating the beta cell proliferation and beta cell population increase at 300 mg/100 ml in 18-day foetal pancreatic explants, but not in 3-day neonatal explants, when compared to the control level of 1OOmg/1OOml. A higher level of glucose (500 mg/100 ml) was ineffective and may even inhibit beta cell population growth. The higher than control levels of glucose (300 mg/100 ml and 500 mg/100 ml) were able to stimulate insulin secretion in neonatal tissue, but not in foetal tissue, although foetal tissue may develop such response later in culture. These results suggest that glucose stimulates beta cell proliferation and insulin secretion through different mechanisms. They further show that the potentiality for beta cell proliferation under glucose stimulation decreases with age of the explants and that the capacity for beta cell to proliferate as a function of glucose stimulation is limited.

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