Glimepiride as insulin sensitizer: increased liver and muscle responses to insulin

Autor(es)

Mori‚ RCT ; Hirabara‚ SM ; Hirata‚ AE ; Okamoto‚ MM ; Machado‚ UF

• Tipo de documento: Artigo Científico
• Fonte: DIABETES OBESITY & METABOLISM; v. 10, n. 7, p. 596-600, 2008.

Resumo

Aim: Glimepiride, a low-potency insulin secretagogue, is as efficient on glycaemic control as other sulphonylureas, suggesting an additional insulin-sensitizer role. The aim of the present study was to confirm the insulin-sensitizer role of glimepiride and to show extra-pancreatic effects of the drug. Methods: Three-month-old monosodium glutamate (MSG)-induced obese insulin-resistant rats were treated (OG) or not treated (O) with glimepiride for 4 weeks and compared with age-matched non-obese rats (C). Insulin sensitivity in whole body, glucose transporter 4 (GLUT4) protein content, glucose uptake and glycogen synthesis in oxidative skeletal muscle and phospho-glycogen synthase kinase (p-GSK3) and glycogen content in liver were analysed. Results: Insulin sensitivity, analysed by the insulin tolerance test, was 30% lower in O than in C rats (p < 0.05), and OG rats recovered this parameter (p < 0.05). In oxidative muscle, glimepiride increased the GLUT4 protein content (50%, p < 0.001) and recovered the obesity-induced reduction (similar to 20%) of the in vitro insulin-stimulated glucose uptake and incorporation into glycogen. In liver, glimepiride increased p-GSK3 (p < 0.01) and glycogen (p < 0.05) contents. Conclusion: The increased GLUT4 protein expression and glucose utilization in oxidative muscle and the increased insulin sensitivity and glycogen storage in liver evidence the insulin-sensitizer effect of glimepiride, which must be important to enable the glimepiride drug to promote an efficient glycaemic control. (AU)

• Processo FAPESP: 02/13692-3 - Efeito do Glimepiride sobre a expressão do gene do GLUT4 em ratos obesos e resistentes à insulina
• Beneficiário: Rosana Cristina Tieko Mori
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 02/07384-4 - Regulação da expressão gênica dos transportadores de glicose no diabetes mellitus: papel na fisiopatologia e potencialidades preventivas e terapêuticas
• Beneficiário: Ubiratan Fabres Machado
• Modalidade de apoio: Auxílio à Pesquisa - Temático