Leptin and insulin induce mutual resistance for nitric oxide synthase III activation in adipocytes
| Autor: | Claude Forest, Anne-Marie Jaubert, Catherine Ribière, Fatoumata Niang, Nadia Mehebik-Mojaat |
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| Rok vydání: | 2009 |
| Předmět: |
Leptin
Male medicine.medical_specialty medicine.medical_treatment Adipose tissue Nitric Oxide Models Biological Biochemistry Rats Sprague-Dawley Phosphatidylinositol 3-Kinases Insulin resistance Insulin receptor substrate Internal medicine Adipocytes medicine Animals Insulin Phosphorylation Molecular Biology Leptin receptor biology digestive oral and skin physiology Cell Biology medicine.disease Rats Enzyme Activation Nitric oxide synthase Insulin receptor Endocrinology Adipose Tissue biology.protein Insulin Resistance Nitric Oxide Synthase hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Cellular Biochemistry. 108:982-988 |
| ISSN: | 1097-4644 0730-2312 |
| Popis: | Obesity-induced hyperleptinemia is frequently associated with insulin resistance suggesting a crosstalk between leptin and insulin signaling pathways. Our aim was to determine whether insulin and leptin together interfere on NOS activation in adipocytes. We examined insulin and leptin-induced nitric oxide synthase (NOS) activity, protein amount and NOS III phosphorylation at Ser1179 in isolated epididymal adipocytes from rat, in the presence or not of inhibitors of kinases implicated in insulin or leptin signaling pathways. Insulin or leptin induced NOS III phosphorylation at Ser1179 leading to increased NO production in rat adipocytes, in agreement with our previous observations. When insulin and leptin at a concentration found in obese rats (10 ng/ml) were combined, NOS activity was not increased, suggesting a negative crosstalk between insulin and leptin signaling mechanisms. Chemical inhibitors of kinases implicated in signaling pathways of insulin, such as PI-3 kinase, or of leptin, such as JAK-2, did not prevent this negative interaction. When leptin signaling was blocked by PKA inhibitors, insulin-induced NOS activity and NOS III phosphorylation at Ser1179 was observed. In the presence of leptin and insulin, (i) IRS-1 was phosphorylated on Ser307 and this effect was prevented by PKA inhibitors, (ii) JAK-2 was dephosphorylated, an effect prevented by SHP-1 inhibitor. A mutual resistance occurs with leptin and insulin. Leptin phosphorylates IRS-1 to induce insulin resistance while insulin dephosphorylates JAK-2 to favor leptin resistance. This interference between insulin and leptin signaling could play a crucial role in insulin- and leptin-resistance correlated with obesity. J. Cell. Biochem. 108: 982–988, 2009. © 2009 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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