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Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Knauf, Claude Cani, Patrice D. Perrin, Christophe Iglesias, Miguel Ángel Araujo Maury, Jean François Bernard, Elodie Benhamed, Fadilha Grémeaux, Thierry Drucker, Daniel J. Kahn, C. Ronald Girard, Jean Tanti, Jean François Delzenne, Nathalie M. Postic, Catherine Burcelin, Remy |
| Copyright Year | 2005 |
| Abstract | Intestinal glucagon-like peptide-1 (GLP-1) is a hormone released into the hepatoportal circulation that stimulates pancreatic insulin secretion. GLP-1 also acts as a neuropeptide to control food intake and cardiovascular functions, but its neural role in glucose homeostasis is unknown. We show that brain GLP-1 controlled whole-body glucose fate during hyperglycemic conditions. In mice undergoing a hyperglycemic hyperinsulinemic clamp, icv administration of the specific GLP-1 receptor antagonist exendin 9-39 (Ex9) increased muscle glucose utilization and glycogen content. This effect did not require muscle insulin action, as it also occurred in muscle insulin receptor KO mice. Conversely, icv infusion of the GLP-1 receptor agonist exendin 4 (Ex4) reduced insulin-stimulated muscle glucose utilization. In hyperglycemia achieved by i.v. infusion of glucose, icv Ex4, but not Ex9, caused a 4-fold increase in insulin secretion and enhanced liver glycogen storage. However, when glucose was infused intragastrically, icv Ex9 infusion lowered insulin secretion and hepatic glycogen levels, whereas no effects of icv Ex4 were observed. In diabetic mice fed a high-fat diet, a 1-month chronic i.p. Ex9 treatment improved glucose tolerance and fasting glycemia. Our data show that during hyperglycemia, brain GLP-1 inhibited muscle glucose utilization and increased insulin secretion to favor hepatic glycogen stores, preparing efficiently for the next fasting state. |
| File Format | PDF HTM / HTML |
| DOI | 10.1172/JCI25764 |
| PubMed reference number | 16322793 |
| Journal | Medline |
| Volume Number | 115 |
| Issue Number | 12 |
| Alternate Webpage(s) | http://dm5migu4zj3pb.cloudfront.net/manuscripts/25000/25764/JCI0525764.pdf |
| Alternate Webpage(s) | http://www.farm.ucl.ac.be/Full-texts-FARM/Knauf-2005-1.pdf |
| Alternate Webpage(s) | https://dm5migu4zj3pb.cloudfront.net/manuscripts/25000/25764/cache/25764.1-20150227135457-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf |
| Alternate Webpage(s) | https://doi.org/10.1172/JCI25764 |
| Journal | The Journal of clinical investigation |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
