Can Insulin Secreting Pancreatic β-cells Provide Novel Insights into the Metabolic Regulation of the DNA Damage Response?

Overview

Journal Biochem Pharmacol

Specialties Biochemistry
Pharmacology

Date 2020 Mar 16

PMID 32171728

Citations 4

Authors

Bryndon J Oleson

John A Corbett

Affiliations

Soon will be listed here.

Abstract

Insulin, produced by pancreatic β-cells, is responsible for the control of whole-body glucose metabolism. Insulin is secreted by pancreatic β-cells in a tightly regulated process that is controlled by the serum level of glucose, glucose sensing and glucose oxidative metabolism. The regulation of intermediary metabolism in β-cells is unique as these cells oxidize glucose to CO on substrate supply while mitochondrial oxidative metabolism occurs on demand, for the production of intermediates or energy production, in most cell types. This review discusses recent findings that the regulation of intermediary metabolism by nitric oxide attenuates the DNA damage response (DDR) and DNA damage-dependent apoptosis in a β-cell selective manner. Specific focus is placed on the mechanisms by which iNOS derived nitric oxide (low micromolar levels) regulates DDR activation via the inhibition of intermediary metabolism. The physiological significance of the association of metabolism, nitric oxide and DDR signaling for cancer biology and diabetes is discussed.

Citing Articles

β-Cell-selective regulation of gene expression by nitric oxide.

Naatz A, Yeo C, Hogg N, Corbett J Am J Physiol Regul Integr Comp Physiol. 2024; 326(6):R552-R566.

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Regulation of ATR-dependent DNA damage response by nitric oxide.

Yeo C, Stancill J, Oleson B, Schnuck J, Stafford J, Naatz A J Biol Chem. 2021; 296:100388.

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Expression of immunoreactive inducible nitric oxide synthase in pancreatic islet cells from newly diagnosed and long-term type 1 diabetic donors is heterogeneous and not disease-associated.

Reddy S, Krogvold L, Martin C, Sun K, Martin O, Al-Ani A Cell Tissue Res. 2021; 384(3):655-674.

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Inhibition of mitochondrial oxidative metabolism attenuates EMCV replication and protects β-cells from virally mediated lysis.

Stafford J, Shaheen Z, Yeo C, Corbett J J Biol Chem. 2020; 295(49):16655-16664.

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