Leptin Therapy Reverses Hyperglycemia in Mice With Streptozotocin-Induced Diabetes, Independent of Hepatic Leptin Signaling
| Autor: | Timothy J. Kieffer, Frank K. Huynh, Rhonda D. Wideman, Roveena M. Sequeira, Scott D. Covey, Jasna Levi, Heather C. Denroche |
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| Rok vydání: | 2011 |
| Předmět: |
Blood Glucose
Leptin Male medicine.medical_specialty endocrine system diseases Endocrinology Diabetes and Metabolism Glucose uptake Adipokine Enzyme-Linked Immunosorbent Assay 030209 endocrinology & metabolism Carbohydrate metabolism Biology Glucagon Diabetes Mellitus Experimental Mice 03 medical and health sciences 0302 clinical medicine Internal medicine Diabetes mellitus Internal Medicine medicine Animals 030304 developmental biology 0303 health sciences Type 1 diabetes Reverse Transcriptase Polymerase Chain Reaction digestive oral and skin physiology nutritional and metabolic diseases Postprandial Period medicine.disease Streptozotocin 3. Good health Mice Inbred C57BL Metabolism Endocrinology Liver Growth Hormone Hyperglycemia Receptors Leptin hormones hormone substitutes and hormone antagonists Signal Transduction medicine.drug |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | OBJECTIVE Leptin therapy has been found to reverse hyperglycemia and prevent mortality in several rodent models of type 1 diabetes. Yet the mechanism of leptin-mediated reversal of hyperglycemia has not been fully defined. The liver is a key organ regulating glucose metabolism and is also a target of leptin action. Thus we hypothesized that exogenous leptin administered to mice with streptozotocin (STZ)-induced diabetes reverses hyperglycemia through direct action on hepatocytes. RESEARCH DESIGN AND METHODS After the induction of diabetes in mice with a high dose of STZ, recombinant mouse leptin was delivered at a supraphysiological dose for 14 days by an osmotic pump implant. We characterized the effect of leptin administration in C57Bl/6J mice with STZ-induced diabetes and then examined whether leptin therapy could reverse STZ-induced hyperglycemia in mice in which hepatic leptin signaling was specifically disrupted. RESULTS Hyperleptinemia reversed hyperglycemia and hyperketonemia in diabetic C57Bl/6J mice and dramatically improved glucose tolerance. These effects were associated with reduced plasma glucagon and growth hormone levels and dramatically enhanced insulin sensitivity, without changes in glucose uptake by skeletal muscle. Leptin therapy also ameliorated STZ-induced hyperglycemia and hyperketonemia in mice with disrupted hepatic leptin signaling to a similar extent as observed in wild-type littermates with STZ-induced diabetes. CONCLUSIONS These observations reveal that hyperleptinemia reverses the symptoms of STZ-induced diabetes in mice and that this action does not require direct leptin signaling in the liver. |
| Databáze: | OpenAIRE |
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