Glimepiride as insulin sensitizer: increased liver and muscle responses to insulin.
OBJECTIVE
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 ( approximately 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.


CONCLUSIONS
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.
Mori
R C T
RC
Hirabara
S M
SM
Hirata
A E
AE
Okamoto
M M
MM
Machado
U F
UF
D000818:Animals; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C057619:glimepiride