Methylglyoxal Impairs Insulin Secretion of Pancreatic β-Cells through Increased Production of ROS and Mitochondrial Dysfunction Mediated by Upregulation of UCP2 and MAPKs

Journal of Diabetes Research
Jinshuang BoQing H Meng

Abstract

Methylglyoxal (MG) is a highly reactive glucose metabolic intermediate and a major precursor of advanced glycation end products. MG level is elevated in hyperglycemic disorders such as diabetes mellitus. Substantial evidence has shown that MG is involved in the pathogenesis of diabetes and diabetic complications. We investigated the impact of MG on insulin secretion by MIN6 and INS-1 cells and the potential mechanisms of this effect. Our study demonstrates that MG impaired insulin secretion by MIN6 or ISN-1 cells in a dose-dependent manner. It increased reactive oxygen species (ROS) production and apoptosis rate in MIN6 or ISN-1 cells and inhibited mitochondrial membrane potential (MMP) and ATP production. Furthermore, the expression of UCP2, JNK, and P38 as well as the phosphorylation JNK and P38 was increased by MG. These effects of MG were attenuated by MG scavenger N-acetyl cysteine. Collectively, these data indicate that MG impairs insulin secretion of pancreatic β-cells through increasing ROS production. High levels of ROS can damage β-cells directly via JNK/P38 upregulation and through activation of UCP2 resulting in reduced MMP and ATP production, leading to β-cell dysfunction and impairment of insulin production.

References

Jan 1, 1993·Molecular Aspects of Medicine·P J Thornalley
Jun 10, 1998·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·S SamecA G Dulloo
Jan 30, 2004·Diabetes·Catherine B ChanMichael B Wheeler
Dec 21, 2004·Free Radical Biology & Medicine·Tuanjie ChangLingyun Wu
Mar 11, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Hideaki KanetoYoshimitsu Yamasaki
Apr 13, 2005·Lancet·Michael StumvollTimon W van Haeften
Jul 11, 2006·The Journal of Clinical Investigation·Marc Prentki, Christopher J Nolan
Feb 17, 2007·Current Opinion in Cell Biology·Claire R Weston, Roger J Davis
Jul 31, 2007·Molecular and Cellular Biochemistry·Xuming Jia, Lingyun Wu
Dec 7, 2007·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·Mei-Ping LuQing H Meng
May 12, 2009·Biochemical Pharmacology·Hui WangLingyun Wu
Mar 13, 2010·Diabetologia·S JitrapakdeeM J MacDonald
Oct 30, 2010·Circulation Research·Ferdinando Giacco, Michael Brownlee
Nov 6, 2010·Antioxidants & Redox Signaling·Christopher RunchelHidenori Ichijo
Mar 20, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Cristina M SenaRaquel M Seiça
Apr 27, 2013·Biochimica Et Biophysica Acta·Yuval SamuniMichael Berk
May 15, 2013·Journal of Diabetes Research·Tiago RodriguesRaquel Seiça
Jul 11, 2013·Journal of Diabetes Research·Jing LiuChun-Ming Wang
Apr 16, 2014·Journal of Diabetes Research·Lingli ZhouLinong Ji
Jun 10, 2014·Lancet·Yuankai Shi, Frank B Hu
Jun 28, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jong Seok LeeEock Kee Hong

❮ Previous
Next ❯

Citations

Dec 1, 2015·International Journal of Biological Macromolecules·Yingnv GaoYu Ou
Jun 19, 2020·Journal of Diabetes and Metabolic Disorders·Alisha ReyazSarita Agarwal
Jul 28, 2017·European Journal of Applied Physiology·Carla Busquets-CortésAntoni Pons
Jul 25, 2019·Cells·Cecilia NigroClaudia Miele
Jun 21, 2019·JCI Insight·Elisabeth LoddJens Kroll
Aug 15, 2020·Frontiers in Immunology·Gholamreza DaryaborKurosh Kalantar
Feb 9, 2021·Journal of Physiology and Biochemistry·Mehdi KaramianMina Hemmati
Feb 15, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Dan-Dan HuangChuanlin Zhu
Mar 23, 2020·Environmental Toxicology and Pharmacology·Muhammad Sajid Hamid AkashKanwal Rehman
Mar 12, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Aramsri MeepromSirichai Adisakwattana

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
ELISA
Protein Assay
PCR
electrophoresis
fluorescence
flow cytometry
chemical modification

Software Mentioned

SPSS

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis