Lixisenatide accelerates restoration of normoglycemia and improves human beta-cell function and survival in diabetic immunodeficient NOD-scid IL-2rg(null) RIP-DTR mice engrafted with human islets

Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy
Chaoxing YangRita Bortell

Abstract

Glucagon-like peptide-1 induces glucose-dependent insulin secretion and, in rodents, increases proliferation and survival of pancreatic beta cells. To investigate the effects on human beta cells, we used immunodeficient mice transplanted with human islets. The goal was to determine whether lixisenatide, a glucagon-like peptide-1 receptor agonist, improves human islet function and survival in vivo. Five independent transplant studies were conducted with human islets from five individual donors. Diabetic human islet-engrafted immunodeficient mice were treated with lixisenatide (50, 150, and 500 µg/kg) or vehicle. Islet function was determined by blood glucose, plasma human insulin/C-peptide, and glucose tolerance tests. Grafts were analyzed for total beta- and alpha-cell number, percent proliferation, and levels of apoptosis. Diabetic mice transplanted with marginal human islet mass and treated with lixisenatide were restored to euglycemia more rapidly than vehicle-treated mice. Glucose tolerance tests, human plasma insulin, and glucose-stimulation indices of lixisenatide-treated mice were significantly improved compared to vehicle-treated mice. The percentages of proliferating or apoptotic beta cells at graft recovery were not d...Continue Reading

Citations

Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sambra D RedickAgata Jurczyk
Nov 2, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Michael A BrehmLeonard D Shultz
Mar 13, 2020·Frontiers in Cell and Developmental Biology·Thomas Aga LegøySimona Chera
Aug 3, 2021·Frontiers in Endocrinology·Peng WangAndrew F Stewart

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Methods Mentioned

BETA
transgenic
enzyme-linked immunosorbent assay
fluorescence microscopy

Software Mentioned

GraphPad Prism

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