Abnormally decreased NO and augmented CO production in islets of the leptin-deficient ob/ob mouse might contribute to explain hyperinsulinemia and islet survival in leptin-resistant type 2 obese diabetes
| Autor: | Javier Jimenez-Feltstrom, Albert Salehi, Ragnar Henningsson, Ingmar Lundquist, Sandra Meidute Abaraviciene |
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| Rok vydání: | 2011 |
| Předmět: |
Blood Glucose
Leptin endocrine system medicine.medical_specialty endocrine system diseases Physiology medicine.medical_treatment Clinical Biochemistry Mice Obese Nitric Oxide Synthase Type II Nitric Oxide Synthase Type I In Vitro Techniques Biology Nitric Oxide Biochemistry Glucagon Islets of Langerhans Mice Cellular and Molecular Neuroscience Endocrinology Hyperinsulinism Internal medicine Insulin Secretion medicine Hyperinsulinemia Animals Humans Insulin Enzyme Assays Carbon Monoxide geography geography.geographical_feature_category Leptin Deficiency ob/ob mouse Islet medicine.disease Insulin oscillation Mice Inbred C57BL Glucose Diabetes Mellitus Type 2 Female |
| Zdroj: | Regulatory Peptides. 170:43-51 |
| ISSN: | 0167-0115 |
| Popis: | The role of the gaseous messengers NO and CO for β-cell function and survival is controversial. We examined this issue in the hyperglycemic-hyperinsulinemic ob/ob mouse, an animal model of type 2 obese diabetes, by studying islets from obese vs lean mice regarding glucose-stimulated insulin release in relation to islet NO and CO production and the influence of modulating peptide hormones. Glucose-stimulated increase in ncNOS-activity in incubated lean islets was converted to a decrease in ob/ob islets associated with markedly increased insulin release. Both types of islets displayed iNOS activity appearing after ~60 min in high-glucose. In ob/ob islets the insulinotropic peptides glucagon, GLP-1 and GIP suppressed NOS activities and amplified glucose-stimulated insulin release. The insulinostatic peptide leptin induced the opposite effects. Suppression of islet CO production inhibited, while stimulation amplified glucose-stimulated insulin release. Nonincubated isolated islets from young and adult obese mice displayed very low ncNOS and negligible iNOS activity. In contrast, production of CO, a NOS inhibitor, was impressively raised. Glucose injections induced strong activities of islet NOS isoforms in lean but not in obese mice and confocal microscopy revealed iNOS expression only in lean islets. Islets from ob/ob mice existing in a hyperglycemic in vivo milieu maintain elevated insulin secretion and protection from glucotoxicity through a general suppression of islet NOS activities achieved by leptin deficiency, high CO production and insulinotropic cyclic-AMP-generating hormones. Such a beneficial effect on islet function and survival might have its clinical counterpart in human leptin-resistant type 2 obese diabetes with hyperinsulinemia. |
| Databáze: | OpenAIRE |
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