scholarly journals Androgens impair β-cell function in a mouse model of polycystic ovary syndrome by activating endoplasmic reticulum stress

2021 ◽  
Author(s):  
Bo Zhu ◽  
Yumei Chen ◽  
Fang Xu ◽  
Xiaolu Shen ◽  
Xuanyu Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Polycystic Ovary Syndrome ◽  
Mouse Model ◽  
Er Stress ◽  
Cell Function ◽  
Polycystic Ovary ◽  
Β Cells ◽  
Β Cell ◽  
Ovary Syndrome ◽  
Β Cell Function

Background: Androgens excess results in endoplasmic reticulum (ER) stress, which is an important cause of β cells dysfunction. Here, we investigated the molecular regulation of androgens excess, ER stress, and β-cell function in polycystic ovary syndrome (PCOS). Methods: PCOS mouse model was established by injection of dehydroepiandrosterone (DHEA). Primary cultured mouse islets were used to detect testosterone (TE)-induced ER stress. The response of ER stress, apoptosis, and hyperinsulinemia were analyzed in INS-1 cells with or without TE exposure. Androgen receptor (AR) antagonist and ER stress inhibitor treatment was performed to evaluate the role of TE in ER stress and proinsulin secretion of PCOS mice. Results: PCOS mice had higher ER stress in islets. TE exposure induced ER stress and apoptosis significantly through sustaining insulin overexpression in β cells, which in turn impaired proinsulin maturation and secretion. Blocking this process could significantly relieve ER stress and apoptosis and improve insulin homeostasis. Conclusion: ER stress activated by androgens excess in PCOS contributes to β cell dysfunction and hyperinsulinemia.

scholarly journals Diazoxide-induced β-cell rest reduces endoplasmic reticulum stress in lipotoxic β-cells

2008 ◽  
Vol 199 (1) ◽  
pp. 41-50 ◽  
Author(s):  
Ernest Sargsyan ◽  
Henrik Ortsäter ◽  
Kristofer Thorn ◽  
Peter Bergsten
Keyword(s):  
Endoplasmic Reticulum ◽  
Insulin Secretion ◽  
Er Stress ◽  
Cell Function ◽  
Β Cells ◽  
Β Cell ◽  
Eukaryotic Translation ◽  
Β Cell Function ◽  
Activating Transcription Factor ◽  
The Unfolded Protein Response

Elevated levels of glucose and lipids are characteristics of individuals with type 2 diabetes mellitus (T2DM). The enhanced nutrient levels have been connected with deterioration of β-cell function and impaired insulin secretion observed in these individuals. A strategy to improve β-cell function in individuals with T2DM has been intermittent administration of KATP channel openers. After such treatment, both the magnitude and kinetics of insulin secretion are markedly improved. In an attempt to further delineate mechanisms of how openers of KATP channels improve β-cell function, the effects of diazoxide on markers of endoplasmic reticulum (ER) stress was determined in β-cells exposed to the fatty acid palmitate. The eukaryotic translation factor 2-alpha kinase 3 (EIF2AK3; also known as PERK) and endoplasmic reticulum to nucleus signaling 1 (ERN1; also known as IRE1) pathways, but not the activating transcription factor (ATF6) pathway of the unfolded protein response, are activated in such lipotoxic β-cells. Inclusion of diazoxide during culture attenuated activation of the EIF2AK3 pathway but not the ERN1 pathway. This attenuation was associated with reduced levels of DNA-damage inducible transcript 3 (DDIT3; also known as CHOP) and β-cell apoptosis was decreased. It is concluded that reduction of ER stress may be a mechanism by which diazoxide improves β-cell function.

scholarly journals β-Cell Function: A Key Pathological Determinant in Polycystic Ovary Syndrome

2005 ◽  
Vol 90 (1) ◽  
pp. 310-315 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Stephen Erickson ◽  
Sidney C. Port ◽  
Robert I. Jennrich ◽  
Stanley G. Korenman
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Cell Function ◽  
Polycystic Ovary ◽  
Β Cell ◽  
Ovary Syndrome ◽  
Β Cell Function ◽  
Pathological Determinant

The Relation Between Clinical Manifestations of Polycystic Ovary Syndrome and β-Cell Function

1993 ◽  
Vol 48 (8) ◽  
pp. 558-559
Author(s):  
R. F. A. Weber ◽  
T. D. Pache ◽  
M. L. Jacobs ◽  
R. Docter ◽  
D. Lynn Loriaux ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Cell Function ◽  
Polycystic Ovary ◽  
Clinical Manifestations ◽  
Β Cell ◽  
Ovary Syndrome ◽  
Β Cell Function

β cell function and insulin resistance in lean cases with polycystic ovary syndrome

2017 ◽  
Vol 33 (11) ◽  
pp. 877-881
Author(s):  
Arunkumar R. Pande ◽  
Ashwani Kumar Guleria ◽  
Sudhanshu Dev Singh ◽  
Manoj Shukla ◽  
Preeti Dabadghao
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Cell Function ◽  
Polycystic Ovary ◽  
Β Cell ◽  
Ovary Syndrome ◽  
Β Cell Function

scholarly journals The effect of atorvastatin on pancreatic beta cell requirement in women with polycystic ovary syndrome

2017 ◽  
Vol 6 (8) ◽  
pp. 811-816 ◽  
Author(s):  
Thozhukat Sathyapalan ◽  
Anne-Marie Coady ◽  
Eric S Kilpatrick ◽  
Stephen L Atkin
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Cell Function ◽  
Polycystic Ovary ◽  
Pancreatic Beta Cell ◽  
Controlled Study ◽  
Β Cell ◽  
Ovary Syndrome ◽  
Increased Risk ◽  
Β Cell Function

Background There is an increased risk of developing T2DM in women with polycystic ovary syndrome (PCOS), and there is evidence that statins improve metabolic parameters in these patients. However, there are some data to show that statins increase the risk of incipient diabetes. Materials and methods We have previously shown that 12 weeks of atorvastatin improves insulin resistance when measured using HOMA-IR. This post hoc analysis was designed to look at the effect of atorvastatin on pancreatic β cell function using HOMA-β in the same study. In this randomised, double-blind placebo controlled study, 40 medication-naïve patients with PCOS were randomised to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo. Results There was a significant reduction in HOMA-β (240 ± 3.2 vs 177 ± 2.3; P value <0.01) after 12 weeks of atorvastatin treatment, which was maintained by metformin in the subsequent 12 weeks. There were no changes in HOMA-β after the placebo or after subsequent metformin treatment. There was no linear correlation between reduction in HOMA-β with improvement of free androgen index (FAI) (r2 = 0.02; P = 0.72), testosterone (r2 = 0.13; P = 0.49), SHBG (r2 = 0.22; P = 0.48), hsCRP (r2 = 0.19; P = 0.64), triglycerides (r2 = 0.09; P = 0.12), total cholesterol (r2 = 0.11; P = 0.32) or LDL-C (r2 = 0.19; P = 0.38). Conclusion Treatment with atorvastatin for 12 weeks in women with PCOS significantly reduced HOMA-β. This could be potentially due to fall in β-cell requirement with improvement of insulin resistance rather than a reduction of β-cell function.

The relation between clinical manifestations of polycystic ovary syndrome and β-cell function

1993 ◽  
Vol 38 (3) ◽  
pp. 295-300 ◽  
Author(s):  
R. F. A. Weber ◽  
T. D. Pache ◽  
M. L. Jacobs ◽  
R. Doctor ◽  
D. Lynn Loriaux ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Cell Function ◽  
Polycystic Ovary ◽  
Clinical Manifestations ◽  
Β Cell ◽  
Ovary Syndrome ◽  
Β Cell Function

scholarly journals Lipotoxicity and β-Cell Failure in Type 2 Diabetes: Oxidative Stress Linked to NADPH Oxidase and ER Stress

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3328
Author(s):  
Eloisa Aparecida Vilas-Boas ◽  
Davidson Correa Almeida ◽  
Leticia Prates Roma ◽  
Fernanda Ortis ◽  
Angelo Rafael Carpinelli
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Nadph Oxidase ◽  
Er Stress ◽  
Cell Function ◽  
Caloric Intake ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function

A high caloric intake, rich in saturated fats, greatly contributes to the development of obesity, which is the leading risk factor for type 2 diabetes (T2D). A persistent caloric surplus increases plasma levels of fatty acids (FAs), especially saturated ones, which were shown to negatively impact pancreatic β-cell function and survival in a process called lipotoxicity. Lipotoxicity in β-cells activates different stress pathways, culminating in β-cells dysfunction and death. Among all stresses, endoplasmic reticulum (ER) stress and oxidative stress have been shown to be strongly correlated. One main source of oxidative stress in pancreatic β-cells appears to be the reactive oxygen species producer NADPH oxidase (NOX) enzyme, which has a role in the glucose-stimulated insulin secretion and in the β-cell demise during both T1 and T2D. In this review, we focus on the acute and chronic effects of FAs and the lipotoxicity-induced β-cell failure during T2D development, with special emphasis on the oxidative stress induced by NOX, the ER stress, and the crosstalk between NOX and ER stress.

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