Glucose-induced glutathione reduction in mitochondria is involved in the first phase of pancreatic β-cell insulin secretion

Liu, Xiaojing; Han, Shuai; Yang, Ying; Wu, Jiarui

doi:10.1016/j.bbrc.2015.07.016

Cited by 13 publications

(8 citation statements)

References 30 publications

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“…31 Moreover, PDI did not facilitate oxidative folding of proinsulin in the ER of pancreatic β cells and had been implicated in retrotranslocation of certain ER-associated degradation (ERAD) substrates. 34 Substantial evidence suggested glutathione was a fundamental function in cellular redox homeostasis, 35,36 and cytosol derived reduced glutathione (GSH) could enter endoplasmic reticulum (ER), which did not only as an indicator of oxidative stress but also played an essential role on the rearrangement of aberrant disulfide bonds. 37 Additionally, reactive oxygen species (ROS) plays an essential role in GSIS, and induction of endogenous antioxidative enzymes in β cells abrogates ROS signaling and reduces GSIS.…”

Section: Discussionmentioning

confidence: 99%

<p>Geniposide Balances the Redox Signaling to Mediate Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells</p>

Liu

Hao

Yin

et al. 2020

DMSO

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Purpose: To investigate the effect of geniposide on the biosynthesis of insulin and the expression protein disulfide isomerase (PDI) and endoplasmic reticulum oxidoreductin 1 (ERO1) in the presence of low (5 mM) and high (25 mM) glucose in pancreatic β cells. Methods: The content of insulin was measured by ELISA, the number of SH groups was determined with the classical chromogenic reagent, 5,5ʹ-dithiobis-(2-nitrobenzoic) acid (DTNB; also known as Ellman's reagent), the expressions of PDI and ERO1 were analyzed by Western blot. Results: Geniposide played contrary roles on the accumulation of H 2 O 2 , the ratio of GSH/ GSSG and the thiol-disulfide balance in the presence of low (5 mM) and high (25 mM) glucose in rat pancreatic INS-1 cells. Geniposide also regulated the protein levels of protein disulfide isomerase (PDI) and endoplasmic reticulum oxidoreductin1 (ERO1), the two key enzymes for the production of H 2 O 2 during the biosynthesis of insulin in INS-1 cells. Conclusion: Geniposide affects glucose-stimulated insulin secretion by modulating the thiol-disulfide balance that is controlled by the redox signaling in pancreatic β cells.

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Section: Discussionmentioning

confidence: 99%

<p>Geniposide Balances the Redox Signaling to Mediate Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells</p>

Liu

Hao

Yin

et al. 2020

DMSO

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“…While more-reduced redox centers drive hyperpolarization of ΔψM in general, fluxes through mitochondrial metabolism and the respiratory chain are also greatly increased during GSIS, making predictions of the redox states of actual ROS-forming centers difficult. ROS levels in turn are also defined by their removal, which is known to increase when glucose is present [91].…”

Section: Discussionmentioning

confidence: 99%

Metabolic activation-driven mitochondrial hyperpolarization predicts insulin secretion in human pancreatic beta-cells

Gerencser

2018

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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Mitochondrial metabolism plays a central role in insulin secretion in pancreatic beta-cells. Generation of protonmotive force and ATP synthesis from glucose-originated pyruvate are critical steps in the canonical pathway of glucose-stimulated insulin secretion. Mitochondrial metabolism is intertwined with pathways that are thought to amplify insulin secretion with mechanisms distinct from the canonical pathway, and the relative importance of these two pathways is controversial. Here I show that glucose-induced mitochondrial membrane potential (MMP) hyperpolarization is necessary for, and predicts, the rate of insulin secretion in primary cultured human beta-cells. When glucose concentration is elevated, increased metabolism results in a substantial MMP hyperpolarization, as well as in increased rates of ATP synthesis and turnover marked by faster cell respiration. Using modular kinetic analysis I explored what properties of cellular energy metabolism enable a large glucose-induced change in MMP in human beta-cells. I found that an ATP-dependent pathway activates glucose or substrate oxidation, acting as a positive feedback in energy metabolism. This activation mechanism is essential for concomitant fast respiration and high MMP, and for a high magnitude glucose-induced MMP hyperpolarization and therefore for insulin secretion.

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“…It was previously shown that the Grx system has positive impact on insulin secretion [16, 46, 47]. Furthermore, tissue-specific expression of Grx was reported [48].…”

Section: Discussionmentioning

confidence: 99%

Differential expression of islet glutaredoxin 1 and 5 with high reactive oxygen species production in a mouse model of diabesity

et al. 2017

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The onset and progression of diabetes mellitus type 2 is highly contingent on the amount of functional beta-cell mass. An underlying cause of beta-cell decay in diabetes is oxidative stress, which markedly affects the insulin producing pancreatic cells due to their poor antioxidant defence capacity. Consequently, disturbances of cellular redox signaling have been implicated to play a major role in beta-cell loss in diabetes mellitus type 2. There is evidence suggesting that the glutaredoxin (Grx) system exerts a protective role for pancreatic islets, but the exact mechanisms have not yet been elucidated. In this study, a mouse model for diabetes mellitus type 2 was used to gain further insight into the significance of Grx for the islets of Langerhans in the diabetic metabolism. We have observed distinct differences in the expression levels of Grx in pancreatic islets between obese, diabetic db mice and lean, non-diabetic controls. This finding is the first report about a decrease of Grx expression levels in pancreatic islets of diabetic mice which was accompanied by declining insulin secretion, increase of reactive oxygen species (ROS) production level, and cell cycle alterations. These data demonstrate the essential role of the Grx system for the beta-cell during metabolic stress which may provide a new target for diabetes mellitus type 2 treatment.

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Glucose-induced glutathione reduction in mitochondria is involved in the first phase of pancreatic β-cell insulin secretion

Cited by 13 publications

References 30 publications

<p>Geniposide Balances the Redox Signaling to Mediate Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells</p>

<p>Geniposide Balances the Redox Signaling to Mediate Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells</p>

Metabolic activation-driven mitochondrial hyperpolarization predicts insulin secretion in human pancreatic beta-cells

Differential expression of islet glutaredoxin 1 and 5 with high reactive oxygen species production in a mouse model of diabesity

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