Increased Insulin Sensitivity in Gsα Knockout Mice
| Autor: | Lee S. Weinstein, Randy Lee, Arthur L. Castle, Min Chen, Kyoko Takeda, Shuhua Yu |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Basal rate Gs alpha subunit Monosaccharide Transport Proteins medicine.medical_treatment Muscle Proteins Stimulation Biochemistry Mice Insulin resistance Internal medicine GTP-Binding Protein alpha Subunits Gs medicine Animals Muscle Skeletal Molecular Biology Mice Knockout Glucose Transporter Type 4 biology Insulin Cell Biology medicine.disease Insulin receptor Endocrinology Knockout mouse biology.protein GLUT4 Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 276:19994-19998 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m010313200 |
| Popis: | The stimulatory guanine nucleotide-binding protein (G(s)) is required for hormone-stimulated cAMP generation. Gnas, the gene encoding the G(s) alpha-subunit, is imprinted, and targeted disruption of this gene in mice leads to distinct phenotypes in heterozygotes depending on whether the maternal (m-/+) or paternal (+/p-) allele is mutated. Notably, m-/+ mice become obese, whereas +/p- mice are thinner than normal. In this study we show that despite these opposite changes in energy metabolism, both m-/+ and +/p- mice have greater sensitivity to insulin, with low to normal fasting glucose levels, low fasting insulin levels, improved glucose tolerance, and exaggerated hypoglycemic response to administered insulin. The combination of increased insulin sensitivity with obesity in m-/+ mice is unusual, because obesity is typically associated with insulin resistance. In skeletal muscles isolated from both m-/+ and +/p- mice, the basal rate of 2-deoxyglucose uptake was normal, whereas the rate of 2-deoxyglucose uptake in response to maximal insulin stimulation was significantly increased. The similar changes in muscle sensitivity to insulin in m-/+ and +/p- mice may reflect the fact that muscle G(s)alpha expression is reduced by approximately 50% in both groups of mice. GLUT4 expression is unaffected in muscles from +/p- mice. Increased responsiveness to insulin is therefore the result of altered insulin signaling and/or GLUT4 translocation. This is the first direct demonstration in a genetically altered in vivo model that G(s)-coupled pathways negatively regulate insulin signaling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|