Volume 10, Issue 7 p. 596-600

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

R. C. T. Mori

R. C. T. Mori

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

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S. M. Hirabara

S. M. Hirabara

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

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A. E. Hirata

A. E. Hirata

Department of Physiology, Federal University of São Paulo, São Paulo, Brazil

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M. M. Okamoto

M. M. Okamoto

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

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U. F. Machado

Corresponding Author

U. F. Machado

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

Dr Ubiratan F. Machado, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP 05508-900, Brazil.
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First published: 28 June 2008
Citations: 32

Abstract

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 (∼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.