Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2022 Sep 23

PMID 36139067

Authors

Eri Mukai

Shimpei Fujimoto

Nobuya Inagaki

Affiliations

Soon will be listed here.

Abstract

The dysfunction of pancreatic β-cells plays a central role in the onset and progression of type 2 diabetes mellitus (T2DM). Insulin secretory defects in β-cells are characterized by a selective impairment of glucose stimulation, and a reduction in glucose-induced ATP production, which is essential for insulin secretion. High glucose metabolism for insulin secretion generates reactive oxygen species (ROS) in mitochondria. In addition, the expression of antioxidant enzymes is very low in β-cells. Therefore, β-cells are easily exposed to oxidative stress. In islet studies using a nonobese T2DM animal model that exhibits selective impairment of glucose-induced insulin secretion (GSIS), quenching ROS generated by glucose stimulation and accumulated under glucose toxicity can improve impaired GSIS. Acute ROS generation and toxicity cause glucose metabolism disorders through different molecular mechanisms. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor, is a master regulator of antioxidant defense and a potential therapeutic target in oxidative stress-related diseases, suggesting the possible involvement of Nrf2 in β-cell dysfunction caused by ROS. In this review, we describe the mechanisms of insulin secretory defects induced by oxidative stress in diabetic β-cells.

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References

Hughes S, Suzuki K, Goto Y . The role of islet secretory function in the development of diabetes in the GK Wistar rat. Diabetologia. 1994; 37(9):863-70. DOI: 10.1007/BF00400940. View

Cattaneo F, Guerra G, Parisi M, De Marinis M, Tafuri D, Cinelli M . Cell-surface receptors transactivation mediated by g protein-coupled receptors. Int J Mol Sci. 2014; 15(11):19700-28. PMC: 4264134. DOI: 10.3390/ijms151119700. View

Prentki M, Matschinsky F, Murthy Madiraju S . Metabolic signaling in fuel-induced insulin secretion. Cell Metab. 2013; 18(2):162-85. DOI: 10.1016/j.cmet.2013.05.018. View

Rutter G, Pullen T, Hodson D, Martinez-Sanchez A . Pancreatic β-cell identity, glucose sensing and the control of insulin secretion. Biochem J. 2015; 466(2):203-18. DOI: 10.1042/BJ20141384. View

Portha B, Giroix M, Tourrel-Cuzin C, Le-Stunff H, Movassat J . The GK rat: a prototype for the study of non-overweight type 2 diabetes. Methods Mol Biol. 2012; 933:125-59. DOI: 10.1007/978-1-62703-068-7_9. View

Pi J, Bai Y, Zhang Q, Wong V, Floering L, Daniel K . Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes. 2007; 56(7):1783-91. DOI: 10.2337/db06-1601. View

Matschinsky F . Regulation of pancreatic beta-cell glucokinase: from basics to therapeutics. Diabetes. 2002; 51 Suppl 3:S394-404. DOI: 10.2337/diabetes.51.2007.s394. View

Joseph J, Jensen M, Ilkayeva O, Palmieri F, Alarcon C, Rhodes C . The mitochondrial citrate/isocitrate carrier plays a regulatory role in glucose-stimulated insulin secretion. J Biol Chem. 2006; 281(47):35624-32. DOI: 10.1074/jbc.M602606200. View

Schuit F, de Vos A, Farfari S, Moens K, Pipeleers D, Brun T . Metabolic fate of glucose in purified islet cells. Glucose-regulated anaplerosis in beta cells. J Biol Chem. 1997; 272(30):18572-9. DOI: 10.1074/jbc.272.30.18572. View

10.

Leloup C, Tourrel-Cuzin C, Magnan C, Karaca M, Castel J, Carneiro L . Mitochondrial reactive oxygen species are obligatory signals for glucose-induced insulin secretion. Diabetes. 2008; 58(3):673-81. PMC: 2646066. DOI: 10.2337/db07-1056. View

11.

Ainscow E, Zhao C, Rutter G . Acute overexpression of lactate dehydrogenase-A perturbs beta-cell mitochondrial metabolism and insulin secretion. Diabetes. 2000; 49(7):1149-55. DOI: 10.2337/diabetes.49.7.1149. View

12.

Thorens B . GLUT2, glucose sensing and glucose homeostasis. Diabetologia. 2014; 58(2):221-32. DOI: 10.1007/s00125-014-3451-1. View

13.

Ingley E . Src family kinases: regulation of their activities, levels and identification of new pathways. Biochim Biophys Acta. 2007; 1784(1):56-65. DOI: 10.1016/j.bbapap.2007.08.012. View

14.

Jha V, Macchia M, Tuccinardi T, Poli G . Three-Dimensional Interactions Analysis of the Anticancer Target c-Src Kinase with Its Inhibitors. Cancers (Basel). 2020; 12(8). PMC: 7466017. DOI: 10.3390/cancers12082327. View

15.

Marselli L, Suleiman M, Masini M, Campani D, Bugliani M, Syed F . Are we overestimating the loss of beta cells in type 2 diabetes?. Diabetologia. 2013; 57(2):362-5. DOI: 10.1007/s00125-013-3098-3. View

16.

Bindokas V, Kuznetsov A, Sreenan S, Polonsky K, Roe M, Philipson L . Visualizing superoxide production in normal and diabetic rat islets of Langerhans. J Biol Chem. 2003; 278(11):9796-801. DOI: 10.1074/jbc.M206913200. View

17.

Tsuura Y, Ishida H, Okamoto Y, Kato S, Sakamoto K, Horie M . Glucose sensitivity of ATP-sensitive K+ channels is impaired in beta-cells of the GK rat. A new genetic model of NIDDM. Diabetes. 1993; 42(10):1446-53. DOI: 10.2337/diab.42.10.1446. View

18.

McCulloch L, van de Bunt M, Braun M, Frayn K, Clark A, Gloyn A . GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic beta cells: implications for understanding genetic association signals at this locus. Mol Genet Metab. 2011; 104(4):648-53. DOI: 10.1016/j.ymgme.2011.08.026. View

19.

Shalev A . Minireview: Thioredoxin-interacting protein: regulation and function in the pancreatic β-cell. Mol Endocrinol. 2014; 28(8):1211-20. PMC: 4116588. DOI: 10.1210/me.2014-1095. View

20.

Ostenson C, Khan A, Abdel-Halim S, Guenifi A, Suzuki K, Goto Y . Abnormal insulin secretion and glucose metabolism in pancreatic islets from the spontaneously diabetic GK rat. Diabetologia. 1993; 36(1):3-8. DOI: 10.1007/BF00399086. View