Cited by 63Pancreatic function and diabetesPeroxisome Proliferator-Activated ReceptorsDiabetes Treatment and Management

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

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Kanda, Yukiko, Shimoda, Masashi, Hamamoto, Sumiko, Tawaramoto, Kazuhito, Kawasaki, Fumiko, Hashiramoto, Mitsuru, Nakashima, Koji, Matsuki, Michihiro +1 more·2010·American Journal of Physiology-Endocrinology and Metabolism

Abstract

Pioglitazone preserves pancreatic β-cell morphology and function in diabetic animal models. In this study, we investigated the molecular mechanisms by which pioglitazone protects β-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 β-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 pioglitazone for 2 wk, rather than 2 days. Morphometric results for proliferative cell number antigen and 4-hydroxy-2-noneal modified protein were consistent with the results of gene expression analysis. The present results strongly suggest that pioglitazone preserves β-cell mass in diabetic mice mostly by two ways; directly, by acceleration of cell differentiation/proliferation and suppression of apoptosis (acute effect); and indirectly, by deceleration of oxidative stress because of amelioration of the underlying metabolic disorder (chronic effect).

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Crossref · 10.1152/ajpendo.00388.2009

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  • Pioglitazone increases β-cell mass by upregulating cell differentiation/proliferation genes.

    “Furthermore, pioglitazone increases β-cell mass by upregulating cell differentiation/proliferation genes.364”

    From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [364]

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Authors
Kanda, Y., Shimoda, M., Hamamoto, S., Tawaramoto, K., Kawasaki, F., Hashiramoto, M., Nakashima, K., Matsuki, M., & Kaku, K.
Affiliations
Kawasaki Medical School (JP)
Corresponding author
Kaku, Kohei
Venue
American Journal of Physiology-Endocrinology and Metabolism
Published
2010-02
Volume
298
Issue
2
Pages
E278-E286
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
OpenAlex
W1970871128
Cited by
63
References
40
Citations by year
2025: 1 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 7 · 2017: 2 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 6 · 2012: 5
FWCI
3.37
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Japan Diabetes Society
  • Kawasaki Medical School
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
pioglitazone, pancreatic beta-cell protection, PPARγ agonists, db/db mice, type 2 diabetes, beta-cell mass, apoptosis, oxidative stress, NADPH oxidase, insulin secretion, beta-cell proliferation, gene expression profiling, islets
MeSH terms
Pioglitazone, Animals, Cell Differentiation, Diabetes Mellitus, Type 2, Disease Models, Animal, Hypoglycemic Agents, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Obese, Obesity, Organ Size, Pancreas, Apoptosis, Oxidative Stress, Gene Expression Profiling, Thiazolidinediones, PPAR gamma, Cell Proliferation, Insulin-Secreting Cells, Mice

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