scholarly journals Low-Level Arsenic Impairs Glucose-Stimulated Insulin Secretion in Pancreatic Beta Cells: Involvement of Cellular Adaptive Response to Oxidative Stress

2010 ◽  
Vol 118 (6) ◽  
pp. 864-870 ◽  
Author(s):  
Jingqi Fu ◽  
Courtney G. Woods ◽  
Einav Yehuda-Shnaidman ◽  
Qiang Zhang ◽  
Victoria Wong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Secretion ◽  
Beta Cells ◽  
Adaptive Response ◽  
Pancreatic Beta Cells ◽  
Low Level ◽  
Glucose Stimulated Insulin Secretion

scholarly journals Precise expression of Fis1 is important for glucose responsiveness of beta cells

2016 ◽  
Vol 230 (1) ◽  
pp. 81-91 ◽  
Author(s):  
Julia Schultz ◽  
Rica Waterstradt ◽  
Tobias Kantowski ◽  
Annekatrin Rickmann ◽  
Florian Reinhardt ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Morphology ◽  
Mitochondrial Network ◽  
Primary Mouse ◽  
Glucose Stimulated Insulin Secretion ◽  
Glucose Responsiveness ◽  
Precise Expression

Mitochondrial network functionality is vital for glucose-stimulated insulin secretion in pancreatic beta cells. Altered mitochondrial dynamics in pancreatic beta cells are thought to trigger the development of type 2 diabetes mellitus. Fission protein 1 (Fis1) might be a key player in this process. Thus, the aim of this study was to investigate mitochondrial morphology in dependence of beta cell function, after knockdown and overexpression of Fis1. We demonstrate that glucose-unresponsive cells with impaired glucose-stimulated insulin secretion (INS1-832/2) showed decreased mitochondrial dynamics compared with glucose-responsive cells (INS1-832/13). Accordingly, mitochondrial morphology visualised using MitoTracker staining differed between the two cell lines. INS1-832/2 cells formed elongated and clustered mitochondria, whereas INS1-832/13 cells showed a homogenous mitochondrial network. Fis1 overexpression using lentiviral transduction significantly improved glucose-stimulated insulin secretion and mitochondrial network homogeneity in glucose-unresponsive cells. Conversely, Fis1 downregulation by shRNA, both in primary mouse beta cells and glucose-responsive INS1-832/13 cells, caused unresponsiveness and significantly greater numbers of elongated mitochondria. Overexpression of FIS1 in primary mouse beta cells indicated an upper limit at which higher FIS1 expression reduced glucose-stimulated insulin secretion. Thus, FIS1 was overexpressed stepwise up to a high concentration in RINm5F cells using the RheoSwitch system. Moderate FIS1 expression improved glucose-stimulated insulin secretion, whereas high expression resulted in loss of glucose responsiveness and in mitochondrial artificial loop structures and clustering. Our data confirm that FIS1 is a key regulator in pancreatic beta cells, because both glucose-stimulated insulin secretion and mitochondrial dynamics were clearly adapted to precise expression levels of this fission protein.

scholarly journals Metabolic concomitants in pure, pancreatic beta cells during glucose-stimulated insulin secretion.

1986 ◽  
Vol 261 (30) ◽  
pp. 14057-14061
Author(s):  
F M Matschinsky ◽  
A K Ghosh ◽  
M D Meglasson ◽  
M Prentki ◽  
V June ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glucose Stimulated Insulin Secretion

scholarly journals Fatty Aldehyde Dehydrogenase (ALDH3A2)-Dependent Neutralization of Advanced Lipid Peroxidation End Products (ALEs) at the Bifurcation of Hormetic and Degenerative Pathways in Pancreatic Beta Cells

Proceedings ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 10
Author(s):  
Sasson
Keyword(s):  
Lipid Peroxidation ◽  
Insulin Secretion ◽  
Palmitic Acid ◽  
Beta Cells ◽  
Aldehyde Dehydrogenase ◽  
Adaptive Response ◽  
Pancreatic Beta Cells ◽  
Fatty Aldehyde ◽  
End Products ◽  
And Function

Hyperglycemia and hyperlipidemia synergistically and adversely impair insulin secretion and ultimately lead to pancreatic beta cell decomposition. We found that both nutrient overload conditions displace arachidonic and linoleic acids from membrane phospholipids and subject them to free radical-mediated peroxidation and generation of advanced lipid peroxidation end products (ALEs), of which the aldehyde 4-hydroxy-2-nonenal (4-HNE) is prominent. When present at high levels this electrophilic molecule binds covalently to nucleophilic moieties in proteins, phospholipids and nucleic acid, modifies their structure and function and leads to severe cellular dysfunction and apoptosis. However, when present at low and unharmful levels this same molecule activates the nuclear receptor PPARδ and augments insulin secretion. The level of endogenous 4-HNE is determined by the extent of lipid peroxidation on one hand, and by enzymatic neutralization of the aldehyde, on the other. The latter step is mediated by enzymatic processes of which the transformation of the aldehyde to the corresponding inactive carboxylic derivative 4-hydroxy-2-nonenoic acid (4-HNA) is significant. The enzyme responsible for this transformation, which belongs to the large family of aldehyde dehydrogenases and selectively neutralizes fatty acid-derived aldehydes, is ALDH3A2, which is also known as fatty aldehyde dehydrogenase (FALDH). Consequently, we hypothesized that the expression level and function of ALDH3A2 may determine the fate of beta cells under nutrient overload conditions: insufficient neutralization of 4-HNE by the enzyme will lead to cell demise, whereas increased expression and function will extend the adaptive response of beta cells. This adaptive response that is characterized with increased insulin secretion enables effective storage of the nutrient surplus in peripheral tissues and organs while minimizing the dire consequences of the nutrient overload. We aimed at investigating the expression pattern of ALDH3A2 in pancreatic beta cells (the INS-1E cell line) under hyperglycemic condition without or with supplementation with saturated fatty acids (e.g., palmitic acid). Our results show significant glucose- and palmitic acid-dependent induction of ALDH3A2 expression in the cells. We also found that the transformation of palmitic acid (16:1) to mono-unsaturated palmitoleic acid (16:1, cis 9) by the enzyme Stearoyl-CoA desaturase-1 (SCD1) decreased the burden of the lipid stress on the cells and abrogated the stimulus for the induction of ALDH3A2. Preliminary experiments indicated that the upregulation of the induction of ALDH3A2 was partly induced by PPARδ. These findings correlate to our previous discovery that the hormetic effects of 4HNE were mediated via activation of this nuclear receptor. In summary, this study assigns a central role to the enzyme ALDH3A2 in the protective mechanism beta cells employ to mitigate detrimental effects of ALEs, and divert them into hormetic agents, that by feedback mechanism through PPARδ increase ALDH3A2 expression.

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