| First Author | Chen M | Year | 2011 |
| Journal | Endocrinology | Volume | 152 |
| Issue | 9 | Pages | 3343-50 |
| PubMed ID | 21771891 | Mgi Jnum | J:177087 |
| Mgi Id | MGI:5293589 | Doi | 10.1210/en.2011-0012 |
| Citation | Chen M, et al. (2011) Absence of the glucagon-like peptide-1 receptor does not affect the metabolic phenotype of mice with liver-specific G(s)alpha deficiency. Endocrinology 152(9):3343-50 |
| abstractText | The stimulatory G protein alpha-subunit (G(s)alpha) couples hormone and other receptors to the generation of intracellular cAMP. We previously showed that mice with liver-specific G(s)alpha deficiency [liver-specific G(s)alpha knockout (LGsKO) mice] had reduced adiposity and improved glucose tolerance associated with increased glucose-stimulated insulin secretion, pancreatic islet hyperplasia, and very high serum glucagon and glucagon-like peptide 1 (GLP-1) levels. Because GLP-1 is known to stimulate insulin secretion and to have effects on energy balance, we mated LGsKO mice with germline GLP-1 receptor (GLP-1R) knockout mice (Glp1r(-/-)) and compared LGsKO to double-knockout (LGs/Glp1r(-/-)) mice to determine the contribution of excess GLP-1R signaling to the LGsKO phenotype. Loss of the GLP-1R failed to reverse most of the metabolic features of LGsKO mice, including reduced fat mass, increased glucose tolerance, and second-phase glucose-stimulated insulin secretion, islet cell hyperplasia, and very high glucagon and GLP-1 levels. However, loss of GLP-1R impaired first-phase insulin secretion in mice with or without liver-specific G(s)alpha deficiency. Thus, excess GLP-1 action (or at least through GLP-1R) does not contribute to the LGsKO metabolic phenotype, and other unknown factors involved in the cross talk between the liver G(s)alpha/cAMP pathway and pancreatic islet function need to be further elucidated. |
