Effects of metformin on compensatory pancreatic β-cell hyperplasia in mice fed a high-fat diet

American Journal of Physiology. Endocrinology and Metabolism
Kazuki TajimaYasuo Terauchi

Abstract

Metformin has been widely used for the treatment of type 2 diabetes. However, the effect of metformin on pancreatic β-cells remains controversial. In this study, we investigated the impacts of treatment with metformin on pancreatic β-cells in a mouse model fed a high-fat diet (HFD), which triggers adaptive β-cell replication. An 8-wk treatment with metformin improved insulin resistance and suppressed the compensatory β-cell hyperplasia induced by HFD-feeding. In contrast, the increment in β-cell mass arising from 60 wk of HFD feeding was similar in mice treated with and those treated without metformin. Interestingly, metformin suppressed β-cell proliferation induced by 1 wk of HFD feeding without any changes in insulin resistance. Metformin directly suppressed glucose-induced β-cell proliferation in islets and INS-1 cells in accordance with a reduction in mammalian target of rapamycin phosphorylation. Taken together, metformin suppressed HFD-induced β-cell proliferation independent of the improvement of insulin resistance, partly via direct actions.

References

Feb 29, 1996·The New England Journal of Medicine·C J Bailey, R C Turner
May 16, 1998·Current Biology : CB·R T Peterson, S L Schreiber
Feb 8, 2002·The New England Journal of Medicine·William C KnowlerUNKNOWN Diabetes Prevention Program Research Group
Sep 10, 2002·American Journal of Physiology. Endocrinology and Metabolism·Bo Ahrén, Giovanni Pacini
Dec 28, 2002·Diabetes·Alexandra E ButlerPeter C Butler
Aug 18, 2004·Genes & Development·Nissim Hay, Nahum Sonenberg
Oct 7, 2004·The Journal of Clinical Investigation·Senta Georgia, Anil Bhushan
Nov 9, 2004·The Journal of Clinical Endocrinology and Metabolism·Piero MarchettiStefano Del Prato
Jul 11, 2006·The Journal of Clinical Investigation·Marc Prentki, Christopher J Nolan
Dec 26, 2006·The Journal of Clinical Investigation·Tanya HansotiaDaniel J Drucker
Jan 30, 2007·Diabetes·Pavlos PissiosRohit N Kulkarni
Apr 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Terumasa OkadaRohit N Kulkarni
Aug 19, 2007·Cell·Na Kyung LeeGerard Karsenty
Oct 3, 2007·The Journal of Clinical Investigation·Tomoaki MoriokaRohit N Kulkarni
Jul 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Latif RachdiErnesto Bernal-Mizrachi
Jul 25, 2009·Molecular Endocrinology·Lu Mei HeJake A Kushner
Oct 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Mira M SachdevaDoris A Stoffers
May 1, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Brad Q StarleyStephen A Harrison
Jul 27, 2010·Journal of Hepatology·Tadanobu NagayaToshifumi Aoyama
May 6, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Guilherme Z RochaJosé B C Carvalheira
Feb 27, 2013·PloS One·Johanne H EllenbroekEelco J de Koning
May 16, 2013·American Journal of Physiology. Endocrinology and Metabolism·Rachel E StamaterisLaura C Alonso
Jul 4, 2013·BMC Cancer·Mingo Ming Ho YungHextan Yuen-Sheung Ngan
Aug 22, 2013·American Journal of Physiology. Endocrinology and Metabolism·K TajimaY Terauchi
Nov 25, 2014·Cell·Peng YiDouglas A Melton
Jan 30, 2015·American Journal of Physiology. Endocrinology and Metabolism·Rockann E MosserMaureen Gannon
Dec 25, 2015·Cell Metabolism·Abdelfattah El OuaamariRohit N Kulkarni

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Citations

Sep 23, 2018·International Journal of Molecular Sciences·Joseph ZhouLixin Li
Aug 15, 2018·American Journal of Physiology. Endocrinology and Metabolism·Maxim D SeferovicMaureen Gannon
Dec 3, 2020·Nutrients·Nicole L Stott, Joseph S Marino
Jan 7, 2021·International Journal of Molecular Sciences·Hui HuangCatherine B Chan
Mar 23, 2019·Romanian Journal of Internal Medicine = Revue Roumaine De Médecine Interne·Larisa PinteMariana Jinga

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Methods Mentioned

BETA
fluorescence microscopy
PCR
Assay
gene knockdown

Software Mentioned

BIOREVO
ImageJ
WinROOF
Multi gauge

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