Adenovirus-mediated chronic 'hyper-resistinemia' leads to in vivo insulin resistance in normal rats
| Autor: | Hiroaki Satoh, M. T. Audrey Nguyen, Jerrold M. Olefsky, Philip D.G. Miles, Isao Usui, Takeshi Imamura |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Adipose tissue AMP-Activated Protein Kinases Fatty Acids Nonesterified Protein Serine-Threonine Kinases Biology Article Adenoviridae Mice Insulin resistance AMP-activated protein kinase Multienzyme Complexes Proto-Oncogene Proteins Internal medicine Glucose Intolerance medicine Hyperinsulinemia Animals Humans Resistin Rats Wistar Muscle Skeletal Metabolic Syndrome Glucose tolerance test medicine.diagnostic_test Insulin Intracellular Signaling Peptides and Proteins nutritional and metabolic diseases General Medicine Glucose Tolerance Test Phosphoproteins medicine.disease Diet Rats Insulin receptor Glucose Endocrinology Adipose Tissue Liver Hormones Ectopic Insulin Receptor Substrate Proteins biology.protein Insulin Resistance Proto-Oncogene Proteins c-akt hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Journal of Clinical Investigation. 114:224-231 |
| ISSN: | 0021-9738 |
| Popis: | We investigated the chronic in vivo effect of resistin on insulin sensitivity and glucose metabolism by overexpressing resistin protein in male Wistar rats using intravenous administration of an adenovirus encoding mouse resistin. After 7 days of elevated resistin levels at a supraphysiological concentration, the animals displayed glucose intolerance and hyperinsulinemia during glucose tolerance tests, and insulin tolerance tests demonstrated an impaired glucose-lowering effect of insulin. The glucose clamp studies were performed at submaximal (4 mU/kg/min) and maximal (25 mU/kg/min) insulin infusion rates and demonstrated the presence of insulin resistance induced by elevated resistin levels. Indeed, the insulin-stimulated glucose infusion rate was decreased by 12-31%; suppression of hepatic glucose output was attenuated by 28-55%; and insulin suppression of circulating FFA levels was inhibited by 7%. Insulin receptor substrate-1 and -2 phosphorylation and Akt activation were impaired in muscle and adipose tissue. Interestingly, activation of AMP-activated protein kinase in skeletal muscle, liver, and adipose tissue was also significantly downregulated. Together, these results indicate that chronic "hyper-resistinemia" leads to whole-body insulin resistance involving impaired insulin signaling in skeletal muscle, liver, and adipose tissue, resulting in glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. Thus elevated resistin levels in normal rats fed a regular chow diet produce many of the features of human syndrome X. |
| Databáze: | OpenAIRE |
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