Iron Regulation of Pancreatic Beta-Cell Functions and Oxidative Stress

Prenatal androgen exposure induces metabolic disorders in female offspring. However, the long-term effect of maternal testosterone excess on glucose metabolism, especially on pancreatic beta cell function, is rarely investigated. Our current study mainly focused on the effects of prenatal testosterone exposure on glucose metabolism and pancreatic beta cell function in aged female offspring. By using maternal mice and their female offspring as animal models, we found that prenatal androgen treatment induced obesity and glucose intolerance in aged offspring. These influences were accompanied by decreased fasting serum insulin concentration, elevated serum triglyceride and testosterone concentrations. Glucose stimulated insulin secretion in pancreatic beta cells of aged female offspring was also affected by prenatal testosterone exposure. We further confirmed that increased serum testosterone contributed to down regulation of Sirtuin 3 expression, activated oxidative stress and impaired pancreatic beta cell function in aged female offspring. Moreover, over-expression of Sirtuin 3 in islets isolated from female offspring treated with prenatal testosterone normalized the oxidative stress level, restored cyclic adenosine monophosphate and adenosine triphosphate generation, which finally improved glucose stimulated insulin secretion in beta cells. Taken together, these results demonstrated that prenatal testosterone exposure caused metabolic disturbance in aged female offspring via suppression of Sirtuin 3 expression and activation of oxidative stress in pancreatic beta cells.

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Role for inducible cAMP early repressor in promoting pancreatic beta cell dysfunction evoked by oxidative stress in human and rat islets

Diabetologia ◽

10.1007/s00125-011-2165-x ◽

2011 ◽

Vol 54 (9) ◽

pp. 2337-2346 ◽

Cited By ~ 22

Author(s):

D. Favre ◽

G. Niederhauser ◽

D. Fahmi ◽

V. Plaisance ◽

S. Brajkovic ◽

...

Keyword(s):

Oxidative Stress ◽

Beta Cell ◽

Pancreatic Beta Cell ◽

Beta Cell Dysfunction ◽

Rat Islets ◽

Cell Dysfunction ◽

Inducible Camp Early Repressor

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Cocoa flavonoid epicatechin protects pancreatic beta cell viability and function against oxidative stress

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201300291 ◽

2013 ◽

Vol 58 (3) ◽

pp. 447-456 ◽

Cited By ~ 59

Author(s):

María Ángeles Martín ◽

Elisa Fernández-Millán ◽

Sonia Ramos ◽

Laura Bravo ◽

Luis Goya

Keyword(s):

Oxidative Stress ◽

Beta Cell ◽

Cell Viability ◽

Pancreatic Beta Cell ◽

And Function ◽

Beta Cell Viability

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Flavonoids Identification and Pancreatic Beta-Cell Protective Effect of Lotus Seedpod

Antioxidants ◽

10.3390/antiox9080658 ◽

2020 ◽

Vol 9 (8) ◽

pp. 658 ◽

Cited By ~ 1

Author(s):

Ming-Shih Lee ◽

Charng-Cherng Chyau ◽

Chi-Ping Wang ◽

Ting-Hsuan Wang ◽

Jing-Hsien Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Beta Cell ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Cell Injury ◽

Pancreatic Beta Cell ◽

B Cell Lymphoma ◽

Pancreatic Cell ◽

Traditional Chinese Herbal Medicine ◽

Lotus Seedpod

Oxidative stress is highly associated with the development of diabetes mellitus (DM), especially pancreatic beta-cell injury. Flavonoids derived from plants have caused important attention in the prevention or treatment of DM. Lotus seedpod belongs to a traditional Chinese herbal medicine and has been indicated to possess antioxidant, anti-age, anti-glycative, and hepatoprotective activities. The purpose of this study was to demonstrate the pancreatic beta-cell protective effects of lotus seedpod aqueous extracts (LSE) against oxidative injury. According to HPLC/ESI-MS-MS method, LSE was confirmed to have flavonoids derivatives, especially quercetin-3-glucuronide (Q3G). In vitro, LSE dose-dependently improved the survival and function of rat pancreatic beta-cells (RIN-m5F) from hydrogen peroxide (H2O2)-mediated loss of cell viability, impairment of insulin secretion, and promotion of oxidative stress. LSE showed potential in decreasing the H2O2-induced occurrence of apoptosis. In addition, H2O2-triggered acidic vesicular organelle formation and microtubule-associated protein light chain 3 (LC3)-II upregulation, markers of autophagy, were increased by LSE. Molecular data explored that antiapoptotic and autophagic effects of LSE, comparable to that of Q3G, might receptively be mediated via phospho-Bcl-2-associated death promoter (p-Bad)/B-cell lymphoma 2 (Bcl-2) and class III phosphatidylinositol-3 kinase (PI3K)/LC3-II signal pathway. In vivo, LSE improved the DM symptoms and pancreatic cell injury better than metformin, a drug that is routinely prescribed to treat DM. These data implied that LSE induces the autophagic signaling, leading to protect beta-cells from oxidative stress-related apoptosis and injury.

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Glucose metabolism and insulin release in mouse beta HC9 cells, as model for wild-type pancreatic beta-cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.5.e846 ◽

1996 ◽

Vol 270 (5) ◽

pp. E846-E857 ◽

Cited By ~ 14

Author(s):

Y. Liang ◽

G. Bai ◽

N. Doliba ◽

C. Buettger ◽

L. Wang ◽

...

Keyword(s):

Glucose Metabolism ◽

Beta Cell ◽

Cell Line ◽

Insulin Release ◽

Cell Lines ◽

Pancreatic Beta Cells ◽

Pancreatic Beta Cell ◽

Glucose Sensing ◽

Cell Functions ◽

Glucose Phosphorylation

Glucose metabolism and its relationship with glucose-induced insulin release were studied in beta HC9 and beta TC3 cells to identify and characterize key factors controlling the intermediary metabolism of glucose and glucose-induced insulin release. The beta HC9 cell line, derived from pancreatic islets with beta-cell hyperplasia, is characterized by a normal concentration-dependency curve for glucose-stimulated insulin release, whereas the beta TC3 cell line, derived from pancreatic beta-cell tumors, shows a marked leftward shift of this curve. Maximum velocity and the Michaelis-Menten constant of glucose uptake in beta HC9 and beta TC3 cells were similar, even though GLUT-2 expression in these two cell lines differed. In both cell lines, the kinetic characteristics of glucose usage, glucose oxidation, and glucose-induced oxygen consumption were similar to those of glucose phosphorylation, indicating that the kinetics of glucose metabolism from the glucose phosphorylation step in the cytosol to the mitochondrial process of oxidative phosphorylation are determined by the glucose-phosphorylating enzyme, that is, by glucokinase in beta HC9 cells and by hexokinase in beta TC3 cells. Thus beta HC9 cells provide an opportunity for the quantitative analysis of glucose metabolism, the associated generation of coupling factors, and other essential beta-cell functions involved in glucose sensing and insulin secretion.

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