| First Author | Neumann UH | Year | 2016 |
| Journal | Mol Metab | Volume | 5 |
| Issue | 8 | Pages | 731-736 |
| PubMed ID | 27656411 | Mgi Jnum | J:270437 |
| Mgi Id | MGI:6274150 | Doi | 10.1016/j.molmet.2016.05.014 |
| Citation | Neumann UH, et al. (2016) Glucagon receptor gene deletion in insulin knockout mice modestly reduces blood glucose and ketones but does not promote survival. Mol Metab 5(8):731-736 |
| abstractText | OBJECTIVE: It has been thought that the depletion of insulin is responsible for the catabolic consequences of diabetes; however, evidence suggests that glucagon also plays a role in diabetes pathogenesis. Glucagon suppression by glucagon receptor (Gcgr) gene deletion, glucagon immunoneutralization, or Gcgr antagonist can reverse or prevent type 1 diabetes in rodents suggesting that dysregulated glucagon is also required for development of diabetic symptoms. However, the models used in these studies were rendered diabetic by chemical- or immune-mediated beta-cell destruction, in which insulin depletion is incomplete. Therefore, it is unclear whether glucagon suppression could overcome the consequence of the complete lack of insulin. METHODS: To directly test this we characterized mice that lack the Gcgr and both insulin genes (GcgrKO/InsKO). RESULTS: In both P1 pups and mice that were kept alive to young adulthood using insulin therapy, blood glucose and plasma ketones were modestly normalized; however, mice survived for only up to 6 days, similar to GcgrHet/InsKO controls. In addition, Gcgr gene deletion was unable to normalize plasma leptin levels, triglycerides, fatty acids, or hepatic cholesterol accumulation compared to GcgrHet/InsKO controls. CONCLUSION: Therefore, the metabolic manifestations associated with a complete lack of insulin cannot be overcome by glucagon receptor gene inactivation. |
