Vitamin D and pancreatic islet function I. Time course for changes in insulin secretion and content during vitamin D deprivation and repletion

1988 ◽  
Vol 11 (8) ◽  
pp. 577-584 ◽  
Author(s):  
H. Labriji-Mestaghanmi ◽  
B. Billaudel ◽  
P. E. Garnier ◽  
W. J. Malaisse ◽  
B. C. J. Sutter
Keyword(s):  
Vitamin D ◽  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Time Course ◽  
Islet Function

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 Chromomycin A2 potently inhibits glucose-stimulated insulin secretion from pancreatic β cells

2018 ◽  
Author(s):  
Michael A Kalwat ◽  
In Hyun Hwang ◽  
Jocelyn Macho ◽  
Magdalena G Grzemska ◽  
Jonathan Z Yang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Natural Product ◽  
Pancreatic Islet ◽  
Islet Function ◽  
Gene Promoters ◽  
Β Cells ◽  
Β Cell ◽  
Regulatory Pathways ◽  
Glucose Stimulated Insulin Secretion ◽  
Cell Gene

ABSTRACTEnhancers or inhibitors of insulin secretion could become therapeutics as well as lead to the identification of requisite β-cell regulatory pathways and increase our understanding of pancreatic islet function. Toward this goal, we previously used an insulin-linked luciferase that is co-secreted with insulin in MIN6 β-cells to perform a high-throughput natural product screen for chronic effects on glucose-stimulated insulin secretion. Using multiple phenotypic analyses, we identified that one of the top natural product hits, chromomycin A2 (CMA2), potently inhibited insulin secretion through at least three mechanisms: disruption of Wnt signaling, interfering with β-cell gene expression, and suppression of triggering calcium (Ca2+) influx. Chronic treatment with CMA2 largely ablated glucose-stimulated insulin secretion even post-washout, but did not inhibit glucose-stimulated generation of ATP or Ca2+ influx. However, by using the KATP channel-opener diazoxide, we uncovered defects in depolarization-induced Ca2+ influx which may contribute to the suppressed secretory response. Glucose-responsive ERK1/2 and S6 phosphorylation were also disrupted by chronic CMA2 treatment. The FUSION bioinformatic database indicated that the phenotypic effects of CMA2 clustered with a number of Wnt/GSK3 pathway-related genes. Consistently, CMA2 decreased GSK3 phosphorylation and suppressed activation of a β-catenin activity reporter. CMA2 and a related compound mithramycin are described to have DNA-interaction properties, possibly abrogating transcription factor binding to critical β-cell gene promoters. We observed that CMA2, but not mithramycin, suppressed expression of PDX1 and UCN3. However, neither expression of INSI/II nor insulin content was affected by chronic CMA2. The mechanisms of CMA2-induced insulin secretion defects may involve components both proximal and distal to Ca2+ influx. Therefore, CMA2 is an example of a chemical that can simultaneously disrupt β-cell function through both non-cytotoxic and cytotoxic mechanisms. Future applications of CMA2 and similar aureolic acid analogs for disease therapies should consider the potential impacts on pancreatic islet function.

scholarly journals Chromomycin A2 potently inhibits glucose-stimulated insulin secretion from pancreatic β cells

2018 ◽  
Vol 150 (12) ◽  
pp. 1747-1757 ◽  
Author(s):  
Michael A. Kalwat ◽  
In Hyun Hwang ◽  
Jocelyn Macho ◽  
Magdalena G. Grzemska ◽  
Jonathan Z. Yang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Cell Function ◽  
Islet Function ◽  
Gene Promoters ◽  
Β Cells ◽  
Β Cell ◽  
Regulatory Pathways ◽  
Glucose Stimulated Insulin Secretion ◽  
Cell Gene

Modulators of insulin secretion could be used to treat diabetes and as tools to investigate β cell regulatory pathways in order to increase our understanding of pancreatic islet function. Toward this goal, we previously used an insulin-linked luciferase that is cosecreted with insulin in MIN6 β cells to perform a high-throughput screen of natural products for chronic effects on glucose-stimulated insulin secretion. In this study, using multiple phenotypic analyses, we found that one of the top natural product hits, chromomycin A2 (CMA2), potently inhibited insulin secretion by at least three potential mechanisms: disruption of Wnt signaling, interference of β cell gene expression, and partial suppression of Ca2+ influx. Chronic treatment with CMA2 largely ablated glucose-stimulated insulin secretion even after washout, but it did not inhibit glucose-stimulated generation of ATP or Ca2+ influx. However, by using the KATP channel opener diazoxide, we uncovered defects in depolarization-induced Ca2+ influx that may contribute to the suppressed secretory response. Glucose-responsive ERK1/2 and S6 phosphorylation were also disrupted by chronic CMA2 treatment. By querying the FUSION bioinformatic database, we revealed that the phenotypic effects of CMA2 cluster with a number of Wnt–GSK3 pathway-related genes. Furthermore, CMA2 consistently decreased GSK3β phosphorylation and suppressed activation of a β-catenin activity reporter. CMA2 and a related compound, mithramycin, are known to have DNA interaction properties, possibly abrogating transcription factor binding to critical β cell gene promoters. We observed that CMA2 but not mithramycin suppressed expression of PDX1 and UCN3. However, neither expression of INSI/II nor insulin content was affected by chronic CMA2. The mechanisms of CMA2-induced insulin secretion defects may involve components both proximal and distal to Ca2+ influx. Therefore, CMA2 is an example of a chemical that can simultaneously disrupt β cell function through both noncytotoxic and cytotoxic mechanisms. Future therapeutic applications of CMA2 and similar aureolic acid analogues should consider their potential effects on pancreatic islet function.

scholarly journals SUN-640 Sex-Specific Difference in REG3G Expression Directs the Maintenance of Islet Function in Offspring of Obese Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jose Casasnovas ◽  
James C Jarrell ◽  
Kok Lim Kua
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Glucose Intolerance ◽  
Maternal Obesity ◽  
Fat Body ◽  
Cell Mass ◽  
Protective Role ◽  
Islet Function ◽  
Β Cell ◽  
The Impact

Abstract Offspring exposed to maternal obesity are more likely to develop pancreatic islet dysfunction, but the underlying mechanistic pathway is unclear. We previously reported that fetal rats exposed to in-utero hyperglycemia had decreased fetal β-cell REG3G, and then developed lower β-cell mass and insulin secretion at adulthood. REG3G is reported to bind EXTL3 which initiates heparan sulfate (HS) synthesize important for pancreatic islet integrity. In this study, we sought the delineate the impact of maternal obesity exposure in altering offspring islet Reg3g and HS, and determine how changes in Reg3g and HS alters offspring islet insulin secretion. We hypothesize that exposure to maternal obesity (MatOb) suppresses offspring β-cell REG3G leading to decreased HS affecting β-cell health/function. We induced maternal obesity by feeding female mice western style diet for 4 weeks, while control mice were fed with regular chow. Offspring were evaluated for fat body mass, glucose intolerance, insulin secretion at postnatal day 21 and at 2-month-old. MatOb mouse offspring had increased fat-to-lean ratio and glucose intolerance but no insulin resistance at postnatal day 21, indicating decreased islet function. We performed islet perifusion to measure insulin induced secretion in postnatal day 21 offsprings. We found that male offspring but not female had impaired insulin secretion. In 2-month old offspring fat-to-lean ratio persisted but only males presented glucose intolerance. We found that pancreatic islet Reg3g expression was higher in MatOb females than males. This was accompanied increased HS in pancreatic islets of MatOb females compared to males. All together our data indicates a sex-specific protective role of Reg3g/HS in pancreatic islet function.

scholarly journals Delta-like Ligand-4-Notch Signaling Inhibition Regulates Pancreatic Islet Function and Insulin Secretion

Cell Reports ◽  
2018 ◽  
Vol 22 (4) ◽  
pp. 895-904 ◽  
Author(s):  
Fabienne Billiard ◽  
Sevasti Karaliota ◽  
Bei Wang ◽  
Dimitrios Stellas ◽  
Ioannis Serafimidis ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Notch Signaling ◽  
Pancreatic Islet ◽  
Islet Function

Vitamin D and pancreatic islet function II. Dynamics of insulin release and cationic fluxes

1988 ◽  
Vol 11 (8) ◽  
pp. 585-593 ◽  
Author(s):  
B. Billaudel ◽  
H. Labriji-Mestaghanmi ◽  
B. C. J. Sutter ◽  
W. J. Malaisse
Keyword(s):  
Vitamin D ◽  
Insulin Release ◽  
Pancreatic Islet ◽  
Islet Function

Soy isoflavones recovers pancreatic islet function and prevents metabolic dysfunction in male rats

2021 ◽  
Author(s):  
Tatiane Aparecida Ribeiro ◽  
Audrei Pavanello ◽  
Laize Peron Tófolo ◽  
Júlio Cezar de Oliveira ◽  
Ana Maria Praxedes de Moraes ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Soy Isoflavones ◽  
Male Rats ◽  
Islet Function ◽  
Metabolic Dysfunction ◽  
Adult Rats ◽  
Long Term Treatment ◽  
Insulin Homeostasis

We tested whether chronic supplementation with soy isoflavones could modulate insulin secretion levels and subsequent recovery of pancreatic islet function as well as prevent metabolic dysfunction induced by early overfeeding in adult male rats. Wistar rats raised in small litters (SL, 3 pups/dam) and normal litters (NL, 9 pups/dam) were used as models of early overfeeding and normal feeding, respectively. At 30 to 90 days old, animals in the SL and NL groups received either soy isoflavones extract (ISO) or water (W) gavage serving as controls. At 90 days old, body weight, visceral fat deposits, glycemia, insulinemia were evaluated. Glucose-insulin homeostasis and pancreatic-islet insulinotropic response were also determined. The early life overnutrition induced by small litter displayed metabolic dysfunction, glucose and insulin homeostasis disruption in adult rats. However, adult SL rats treated with soy isoflavones showed improvement in glucose tolerance, insulin sensitivity, insulinemia, fat tissue accretion and body weight gain, compared with SL-W group. Pancreatic-islet response to cholinergic, adrenergic and glucose stimuli was improved in both isoflavone-treated groups. In addition, different isoflavone concentrations increased glucose-stimulated insulin secretion in islets of all groups with higher magnitude in both NL and SL isoflavone treated groups. These results indicate that long-term treatment with soy isoflavones inhibits early overfeeding-induced metabolic dysfunction in adult rats and modulated the process of insulin secretion in pancreatic islets.

scholarly journals Abnormal Glucose Homeostasis and Pancreatic Islet Function in Mice with Inactivation of the Fem1b Gene

2005 ◽  
Vol 25 (15) ◽  
pp. 6570-6577 ◽  
Author(s):  
Deyin Lu ◽  
Tereza Ventura-Holman ◽  
Jing Li ◽  
Robert W. McMurray ◽  
Jose S. Subauste ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Sex Determination ◽  
Pancreatic Islet ◽  
Glucose Homeostasis ◽  
Islet Function ◽  
Β Cells

ABSTRACT Type 2 diabetes mellitus is a disorder of glucose homeostasis involving complex gene and environmental interactions that are incompletely understood. Mammalian homologs of nematode sex determination genes have recently been implicated in glucose homeostasis and type 2 diabetes mellitus. These are the Hedgehog receptor Patched and Calpain-10, which have homology to the nematode tra-2 and tra-3 sex determination genes, respectively. Here, we have developed Fem1b knockout (Fem1b-KO) mice, with targeted inactivation of Fem1b, a homolog of the nematode fem-1 sex determination gene. We show that the Fem1b-KO mice display abnormal glucose tolerance and that this is due predominantly to defective glucose-stimulated insulin secretion. Arginine-stimulated insulin secretion is also affected. The Fem1b gene is expressed in pancreatic islets, within both β cells and non-β cells, and is highly expressed in INS-1E cells, a pancreatic β-cell line. In conclusion, these data implicate Fem1b in pancreatic islet function and insulin secretion, strengthening evidence that a genetic pathway homologous to nematode sex determination may be involved in glucose homeostasis and suggesting novel genes and processes as potential candidates in the pathogenesis of diabetes mellitus.

Sign in / Sign up

Export Citation Format

Share Document