Molecular mechanism by which pioglitazone preserves pancreatic beta-cells in obese diabetic mice: evidence for acute and chronic actions as a PPARgamma agonist.

American Journal of Physiology. Endocrinology and Metabolism
Yukiko KandaKohei Kaku

Abstract

Pioglitazone preserves pancreatic beta-cell morphology and function in diabetic animal models. In this study, we investigated the molecular mechanisms by which pioglitazone protects beta-cells in diabetic db/db mice. In addition to the morphological analysis of the islets, gene expression profiles of the pancreatic islet were analyzed using laser capture microdissection and were compared with real-time RT-PCR of db/db and nondiabetic m/m mice treated with or without pioglitazone for 2 wk or 2 days. Pioglitazone treatment (2 wk) ameliorated dysmetabolism, increased islet insulin content, restored glucose-stimulated insulin secretion, and preserved beta-cell mass in db/db mice but had no significant effects in m/m mice. Pioglitazone upregulated genes that promote cell differentiation/proliferation in diabetic and nondiabetic mice. In db/db mice, pioglitazone downregulated the apoptosis-promoting caspase-activated DNase gene and upregulated anti-apoptosis-related genes. The above-mentioned effects of pioglitazone treatment were also observed after 2 days of treatment. By contrast, the oxidative stress-promoting NADPH oxidase gene was downregulated, and antioxidative stress-related genes were upregulated, in db/db mice treated with...Continue Reading

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Citations

Jan 10, 2013·Diabetology & Metabolic Syndrome·Rodrigo N LamounierMaria Lúcia Corrêa-Giannella
Apr 1, 2014·Metabolism: Clinical and Experimental·Hiroto HayashiNoriyasu Hirasawa
Jun 7, 2013·Chronobiology International·Shu-Chuan YangKun-Ruey Shieh
Jan 28, 2015·Molecular and Cellular Endocrinology·Lihua ChenPo Sing Leung
Jan 15, 2013·American Journal of Obstetrics and Gynecology·Arshag KalanderianEgle Bytautiene
Oct 28, 2015·Biochemical and Biophysical Research Communications·Seizo OkauchiHideaki Kaneto
Mar 11, 2018·Journal of Cellular and Molecular Medicine·Katerina KapodistriaParaskevi Kitsiou
Feb 7, 2018·Journal of Diabetes Investigation·Hidenori HirukawaUNKNOWN Pioglitazone and Sulfonylurea Remission from Type 2 Diabetes Mellitus and Anti-Atherosclerosis in Japan (PREVENT-J) study gr
Sep 13, 2017·International Journal of Obesity : Journal of the International Association for the Study of Obesity·G KimB-S Cha
Mar 12, 2016·Experimental & Molecular Medicine·Pia V RöderWeiping Han
Oct 2, 2012·Molecular Pharmacology·Martina DüferGisela Drews
Aug 18, 2017·Critical Reviews in Toxicology·Melissa A DavidsonDaniel Krewski
Aug 19, 2011·American Journal of Physiology. Endocrinology and Metabolism·Sung Soo ChungKyong Soo Park

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Methods Mentioned

BETA
ELISA
laser capture microdissection
PCR
electrophoresis

Software Mentioned

StatView
NIH Image
Primer Express
SAS

Related Concepts

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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