Distinct effects of dipeptidyl peptidase-4 inhibitor and glucagon-like peptide-1 receptor agonist on islet morphology and function

Endocrine
Asuka MoritaTakashi Miki

Abstract

Although the two anti-diabetic drugs, dipeptidyl peptidase-4 inhibitors (DPP4is) and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP1RAs), have distinct effects on the dynamics of circulating incretins, little is known of the difference in their consequences on morphology and function of pancreatic islets. We examined these in a mouse model of β cell injury/regeneration. The model mice were generated so as to express diphtheria toxin (DT) receptor and a fluorescent protein (Tomato) specifically in β cells. The mice were treated with a DPP4i (MK-0626) and a GLP1RA (liraglutide), singly or doubly, and the morphology and function of the islets were compared. Prior administration of MK-0626 and/or liraglutide similarly protected β cells from DT-induced cell death, indicating that enhanced GLP-1 signaling can account for the cytoprotection. However, 2-week intervention of MK-0626 and/or liraglutide in DT-injected mice resulted in different islet morphology and function: β cell proliferation and glucose-stimulated insulin secretion (GSIS) were increased by MK-0626 but not by liraglutide; α cell mass was decreased by liraglutide but not by MK-0626. Although liraglutide administration nullified MK-0626-induced β cell proliferati...Continue Reading

References

Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·T MikiS Seino
Dec 28, 2002·Diabetes·Alexandra E ButlerPeter C Butler
May 3, 2003·The Journal of Clinical Endocrinology and Metabolism·Kun Ho YoonSusan Bonner-Weir
Dec 6, 2005·The Journal of Biological Chemistry·Ji-Yeon LeeLothar Hennighausen
Dec 6, 2006·The New England Journal of Medicine·Steven E KahnUNKNOWN ADOPT Study Group
Sep 6, 2007·The Journal of Clinical Investigation·Tomer NirYuval Dor
Oct 18, 2008·Diabetes, Obesity & Metabolism·J RahierJ C Henquin
Jul 21, 2010·Journal of Molecular Neuroscience : MN·Yusuke SakuraiAkemichi Baba
Aug 9, 2011·Progress in Biophysics and Molecular Biology·Daisuke Yabe, Yutaka Seino
Apr 6, 2012·The New England Journal of Medicine·Faramarz Ismail-Beigi
Aug 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Young LeeRoger H Unger
Apr 3, 2013·Cold Spring Harbor Perspectives in Biology·David R McIlwainTak W Mak
May 21, 2013·Cell Metabolism·Jonathan E Campbell, Daniel J Drucker
Dec 5, 2014·World Journal of Gastroenterology : WJG·Tatsuya OhyamaMasanobu Yamada

❮ Previous
Next ❯

Citations

Apr 30, 2016·Diabetes & Metabolism Journal·Suk Chon, Jean François Gautier
Mar 11, 2018·Journal of Cellular and Molecular Medicine·Katerina KapodistriaParaskevi Kitsiou
Jun 7, 2020·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Naoto KatakamiUNKNOWN J-DISCOVER Study Group

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antidiabetic Cellular Plasticity

This feed focuses on mechanisms that underlie cellular plasticity as a treatment for diabetes and other degenerative diseases.

Cardiovascular Biology of GLP-1

Glucagon-like peptide 1 (GLP-1) plays a role in glucose metabolism, energy homeostasis, and inflammation suppression. GLP-1 receptor signaling has been shown to impact cardiovascular function. This feed focuses on the role of GLP-1 and GLP-1 receptor agonists on cardiovascular biology.