GLP-1 signalling compensates for impaired insulin signalling in regulating beta cell proliferation in βIRKO mice

Diabetologia
Dan KawamoriRohit N Kulkarni

Abstract

We aimed to investigate potential interactions between insulin and glucagon-like peptide (GLP)-1 signalling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function. Beta cell-specific insulin receptor knockout (βIRKO) mice, which exhibit beta cell dysfunction and an age-dependent decrease in beta cell mass, were treated with the dipeptidyl peptidase-4 inhibitor vildagliptin. Following this, glucose homeostasis and beta cell proliferation were evaluated and underlying molecular mechanisms were investigated. The sustained elevation in circulating GLP-1 levels, caused by treatment of the knockout mice with vildagliptin for 6 weeks, significantly improved glucose tolerance secondary to enhanced insulin secretion and proliferation of beta cells. Treating βIRKO beta cell lines with the GLP-1 analogue, exendin-4, promoted Akt phosphorylation and protein expression of cyclins A, D1 and E two- to threefold, in addition to cyclin D2. Pancreases from the vildagliptin-treated βIRKO mice exhibited increased cyclin D1 expression, while cyclin D2 expression was impaired. Activation of GLP-1 signalling compensates for impaired growth factor (in...Continue Reading

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Citations

Nov 2, 2017·International Journal of Obesity : Journal of the International Association for the Study of Obesity·M DíazL Ibáñez
Aug 29, 2018·International Journal of Molecular Sciences·Julien B PujolEl Hadji M Dioum
Nov 20, 2018·Antioxidants & Redox Signaling·Petr JežekLydie Plecitá-Hlavatá
Jul 19, 2019·Diabetes/metabolism Research and Reviews·Bingwen LiuZhiguang Zhou
Oct 31, 2020·The Journal of Clinical Endocrinology and Metabolism·Andrea Mario BollaLorenzo Piemonti
Nov 27, 2019·Molecular Metabolism·T D MüllerM H Tschöp
May 20, 2021·Oxidative Medicine and Cellular Longevity·Habib YaribeygiAmirhossein Sahebkar

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