| First Author | Lin HV | Year | 2011 |
| Journal | Diabetes | Volume | 60 |
| Issue | 3 | Pages | 700-9 |
| PubMed ID | 21266328 | Mgi Jnum | J:169404 |
| Mgi Id | MGI:4940936 | Doi | 10.2337/db10-1056 |
| Citation | Lin HV, et al. (2011) Diabetes in mice with selective impairment of insulin action in glut4-expressing tissues. Diabetes 60(3):700-9 |
| abstractText | OBJECTIVE Impaired insulin-dependent glucose disposal in muscle and fat is a harbinger of type 2 diabetes, but murine models of selective insulin resistance at these two sites are conspicuous by their failure to cause hyperglycemia. A defining feature of muscle and fat vis-a-vis insulin signaling is that they both express the insulin-sensitive glucose transporter Glut4. We hypothesized that diabetes is the result of impaired insulin signaling in all Glut4-expressing tissues. RESEARCH DESIGN AND METHODS To test the hypothesis, we generated mice lacking insulin receptors at these sites ('GIRKO' mice), including muscle, fat, and a subset of Glut4-positive neurons scattered throughout the central nervous system. RESULTS GIRKO mice develop diabetes with high frequency because of reduced glucose uptake in peripheral organs, excessive hepatic glucose production, and beta-cell failure. CONCLUSIONS The conceptual advance of the present findings lies in the identification of a tissue constellation that melds cell-autonomous mechanisms of insulin resistance (in muscle/fat) with cell-nonautonomous mechanisms (in liver and beta-cell) to cause overt diabetes. The data are consistent with the identification of Glut4 neurons as a distinct neuroanatomic entity with a likely metabolic role. |
