| First Author | Huang X | Year | 2008 |
| Journal | Diabetes | Volume | 57 |
| Issue | 1 | Pages | 77-85 |
| PubMed ID | 17928396 | Mgi Jnum | J:132416 |
| Mgi Id | MGI:3775902 | Doi | 10.2337/db07-0599 |
| Citation | Huang X, et al. (2008) Resistance to diet-induced obesity and improved insulin sensitivity in mice with a regulator of G protein signaling-insensitive G184S Gnai2 allele. Diabetes 57(1):77-85 |
| abstractText | OBJECTIVE: Guanine nucleotide binding protein (G protein)-mediated signaling plays major roles in endocrine/metabolic function. Regulators of G protein signaling (RGSs, or RGS proteins) are responsible for the subsecond turn off of G protein signaling and are inhibitors of signal transduction in vitro, but the physiological function of RGS proteins remains poorly defined in part because of functional redundancy. RESEARCH DESIGN AND METHODS: We explore the role of RGS proteins and G alpha(i2) in the physiologic regulation of body weight and glucose homeostasis by studying genomic 'knock-in' mice expressing RGS-insensitive G alpha(i2) with a G184S mutation that blocks RGS protein binding and GTPase acceleration. RESULTS: Homozygous G alpha(i2)(G184S) knock-in mice show slightly reduced adiposity. On a high-fat diet, male G alpha(i2)(G184S) mice are resistant to weight gain, have decreased body fat, and are protected from insulin resistance. This appears to be a result of increased energy expenditure. Both male and female G alpha(i2)(G184S) mice on a high-fat diet also exhibit enhanced insulin sensitivity and increased glucose tolerance despite females having similar weight gain and adiposity compared with wild-type female mice. CONCLUSIONS: RGS proteins and G alpha(i2) signaling play important roles in the control of insulin sensitivity and glucose metabolism. Identification of the specific RGS proteins involved might permit their consideration as potential therapeutic targets for obesity-related insulin resistance and type 2 diabetes. |
