Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice.

Abstract

Glucagon, the counter-regulatory hormone to insulin, is secreted from pancreatic alpha cells in response to low blood glucose. To examine the role of glucagon in glucose homeostasis, mice were generated with a null mutation of the glucagon receptor (Gcgr(-/-)). These mice display lower blood glucose levels throughout the day and improved glucose tolerance but similar insulin levels compared with control animals. Gcgr(-/-) mice displayed supraphysiological glucagon levels associated with postnatal enlargement of the pancreas and hyperplasia of islets due predominantly to alpha cell, and to a lesser extent, delta cell proliferation. In addition, increased proglucagon expression and processing resulted in increased pancreatic glucogen-like peptide 1 (GLP-1) (1-37) and GLP-1 amide (1-36 amide) content and a 3- to 10-fold increase in circulating GLP-1 amide. Gcgr(-/-) mice also displayed reduced adiposity and leptin levels but normal body weight, food intake, and energy expenditure. These data indicate that glucagon is essential for maintenance of normal glycemia and postnatal regulation of islet and alpha and delta cell numbers. Furthermore, the lean phenotype of Gcgr(-/-) mice suggests glucagon action may be involved in the regulation of whole body composition.

7 Figures and Tables

05001000'02'04'06'08'10'12'14'16
Citations per Year

4,828 Citations

Semantic Scholar estimates that this publication has 4,828 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Gelling2003LowerBG, title={Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice.}, author={Richard Wayne Gelling and Xiu Quan Du and Darwin Sorento Dichmann and J . J . Romer and Hui Ling Huang and L Y Cui and Silvana Obici and Buyun Tang and Jens Juul Holst and Christian Fledelius and Peter Johansen and Luca Rossetti and Linda A. Jelicks and Palle Serup and Eiji Nishimura and Maureen J. Charron}, journal={Proceedings of the National Academy of Sciences of the United States of America}, year={2003}, volume={100 3}, pages={1438-43} }