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Glucagon-like peptide-1 receptor agonist treatment reduces beta cell mass in normoglycaemic mice

J H Ellenbroek1, H A M Töns, M J A Westerouen van Meeteren

  • 1Department of Nephrology, Leiden University Medical Center, Postal Zone C7-P, PO Box 9600, 2300 RC Leiden, the Netherlands.

Diabetologia
|June 18, 2013
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like liraglutide improve insulin sensitivity and beta cell function. However, in normoglycaemic mice, GLP-1RA treatment reduces beta cell mass while maintaining overall glycaemic control.

Area of Science:

  • Endocrinology
  • Metabolic research
  • Diabetes research

Background:

  • Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), are established treatments for type 2 diabetes.
  • GLP-1RAs have demonstrated the ability to increase beta cell mass in animal models of diabetes.
  • The impact of GLP-1RAs on beta cell mass in non-diabetic, normoglycaemic individuals remains unclear, particularly concerning their use in managing obesity and cardiovascular disease.

Purpose of the Study:

  • To investigate the effects of the GLP-1RA liraglutide on beta cell mass and function in normoglycaemic mice.
  • To determine if liraglutide influences beta cell proliferation and mass under non-diabetic conditions.
  • To assess the impact of liraglutide on insulin sensitivity and glucose metabolism in normoglycaemic mice, with and without a high-fat diet.

Main Methods:

  • C57BL/6J mice were administered liraglutide or a placebo (PBS) and maintained on either a control or high-fat diet (HFD) for 6 weeks.
  • Glucose and insulin tolerance tests were conducted after 6 weeks of treatment.
  • Beta cell proliferation was assessed using BrdU labeling, and pancreatic tissue was analyzed via histology and islet isolation for glucose-induced insulin secretion assays.

Main Results:

  • Liraglutide treatment for 6 weeks enhanced insulin sensitivity and mitigated HFD-induced insulin resistance.
  • A significant reduction in beta cell mass was observed in liraglutide-treated mice (both control and HFD groups) at 6 weeks, correlating with decreased beta cell proliferation after 1 week.
  • Islets from liraglutide-treated normoglycaemic mice exhibited improved glucose-induced insulin secretion, despite the reduction in beta cell mass.

Conclusions:

  • GLP-1RA treatment, exemplified by liraglutide, can improve insulin sensitivity and beta cell function in normoglycaemic conditions.
  • The observed increase in insulin sensitivity and function is associated with a decrease in beta cell mass, suggesting a regulatory mechanism to maintain normoglycaemia.
  • These findings highlight a potential role for GLP-1RAs in metabolic regulation beyond their established use in diabetes treatment.

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