Des-aspartate-angiotensin-I and angiotensin IV improve glucose tolerance and insulin signalling in diet-induced hyperglycaemic mice
Autor: | Yong-Chiat Wong, Meng-Kwoon Sim, Kok-Onn Lee |
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Rok vydání: | 2011 |
Předmět: |
Blood Glucose
Male medicine.medical_specialty medicine.medical_treatment Indomethacin Biochemistry Drug Administration Schedule Losartan Receptor Angiotensin Type 1 Mice Phosphatidylinositol 3-Kinases Insulin resistance Dietary Sucrose Diabetes mellitus Internal medicine Glucose Intolerance Renin–angiotensin system medicine Hyperinsulinemia Animals Insulin Cystinyl Aminopeptidase Protein kinase B PI3K/AKT/mTOR pathway Pharmacology biology Angiotensin II nutritional and metabolic diseases Janus Kinase 2 medicine.disease Dietary Fats Mice Inbred C57BL Endocrinology Hyperglycemia Insulin Receptor Substrate Proteins biology.protein Angiotensin I hormones hormone substitutes and hormone antagonists GLUT4 Signal Transduction |
Zdroj: | Biochemical Pharmacology. 82:1198-1208 |
ISSN: | 0006-2952 |
Popis: | Although clinical studies suggested that blockade of the renin-angiotensin system may prevent diabetes, the mechanism is uncertain. As a follow-up to an earlier study, we investigated how des-aspartate-angiotensin-1 (DAA-1) and its metabolite, angiotensin IV (Ang-IV) improved glucose tolerance in diet-induced hyperglycaemic mice. Male C57BL/6J mice were fed a high-fat-high-sucrose (HFD) or normal (ND) diet for 52 weeks. HFD animals were orally administered either DAA-I (600 nmol/kg/day), Ang-IV (400 nmol/kg/day) or distilled water. Body weight, blood glucose and insulin were measured fortnightly. Inflammatory and insulin signalling transducers that are implicated in hyperglycaemia were analyzed in skeletal muscles at 52 weeks. HFD animals developed hyperglycemia, hyperinsulinemia and obesity. DAA-I and Ang-IV improved glucose tolerance but had no effect on hyperinsulinemia and obesity. Skeletal muscles of HFD animals showed increased level of ROS, gp91 of NADPH oxidase, pJNK and AT 1 R-JAK-2-IRS-1 complex. Both DAA-I and Ang-IV attenuated these increases. Insulin-induced activation of IR, IRS-1, IRS-1-PI3K coupling, phosphorylation of Akt, and GLUT4 translocation were attenuated in skeletal muscles of HFD animals. The attenuation was significantly ameliorated in DAA-I-treated HFD animals. In corresponding Ang-IV treated animals, insulin induced IRAP and PI3K interaction, activation of pAkt and GLUT4 translocation, but no corresponding activation of IR, IRS-1 and IRS-1-PI3 K coupling were observed. DAA-I and Ang-IV improved glucose tolerance, insulin signalling, and para-inflammatory processes linked to hyperglycaemia. DAA-I acts via the angiotensin AT 1 receptor and activates the insulin pathway. Ang-IV acts via IRAP, which couples PI3K and activates the later part of the insulin pathway. |
Databáze: | OpenAIRE |
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