Glimepiride improves insulin sensitivity in MSG-obese rats without aggravating the obesity (2008)
- Authors:
- Autor USP: MACHADO, UBIRATAN FABRES - ICB
- Unidade: ICB
- Assunto: FISIOLOGIA
- Language: Português
- Abstract: Introduction: Glimepiride is an anti-hyperglycemic drug used in the treatment of DM2 to increase insulin secretion. Compared to other compounds belonging to its group (sulfonyurea drugs), glimepiride presents low affinity to the specific receptors in the B cells, but its effect on glycemic control is maintained, indicating a higher efficacy in ameliorating insulin sensitivity. In vitro, the glimepiride drug acutely stimulates GLUT4 translocation and increases glucose uptake. Notwithstanding, the molecular mechanisms activated in vivo are yet to be clarified. Objective: To identify extra-pancreatic responses to the glimepiride treatment which could explain the increase in the whole body insulin sensitivity. Methods: Insulin resistance was induced in male Wistar rats by neonatal treatment with MSG (4mg/g/day, s.c.). At the age of three months, obese animals received glimepiride (0.1mg/kg/day, in the drinkig water) for 4 weeks, resulting in 3 experimental groups: control (C), obese (O) and obese treated with glimepiride (OG). Animals were then submitted to: 1) insulin tolerance tests (ITT), 2) GLUT4 mRNA and protein analyses in adipose tissue and soleus, 3)glucose uptake/ incorporation to glycogen assays in soleus in vitro, 4) hepatic glycogen content analysis and 5) hepatic p-GSK3 (phospho- glycogen sinthase kinase 3) content analysis. Results: O rats were resistant to insulin, showing significantly slower glucose decay constant after an insulin overload (3,26%/min, p <0,05 vs. C: 4,67%/min and OG: 4,53%/min). This result was accompanied by tissue-specific alterations in the GLUT4 expression: In adipose tissue, both GLUT4 mRNA and protein contents were significantly higher in the obese animals (30% and 100% increases, p < 0,05 vs. C, respectively), and these features were completely abolished by the glimepiride treatment. ) This effect must have been important to avoid the exacerbation of the obesity, in spite of the elevated insulinemia due to the secretagogue effect of the drug. In soleus muscle, a 30% increase in GLUT4 mRNA level was observed in O rats (p < 0.05 vs. C), but the protein expression was similar to C (p > 0,05). The glimepiride drug significantly elevated the GLUT4 protein in 50% (OG vs. O, p < 0,05). When functionally evaluated, the O soleus presented lower insulin-stimulated glucose uptake (p < 0,01) and lower [U-14C]-D-glucose incorporation to glycogen (p < 0,05) as compared to the other groups. Similarly, in the liver, O rats had lower glycogen content (p < 0,05 vs. C and OG) and lower p-GSK3 content (p < 0,01 vs. C and OG). Conclusion: The glimepiride drug increased GLUT4 expression in the oxidative muscle fibres of insulin resistant animals. Functionally, this effect was reflected in an ameliorated insulin-stimulated glucose uptake and glycogen synthesis in these fibres. These effects, added to the increased glycogenesis observed in the liver, provide the glimepiride drug its insulin sensitizereffect, since the hepatic and muscular tissues are the most important insulin-stimulated glucose disposal sites. Additionally, the reduced GLUT4 content in adipose tissue of OG rats avoided the aggravation of the obesity.
- Imprenta:
- Source:
- Título do periódico: Arquivos Brasileiros de Endocrinologia e Metabologia
- Volume/Número/Paginação/Ano: v. 52, suppl. 2, 2008
- Conference titles: Congresso Paulista de Diabetes e Metabolismo
-
ABNT
MORI, R. C. T. e MACHADO, Ubiratan Fabres. Glimepiride improves insulin sensitivity in MSG-obese rats without aggravating the obesity. Arquivos Brasileiros de Endocrinologia e Metabologia. São Paulo: Instituto de Ciências Biomédicas, Universidade de São Paulo. . Acesso em: 23 abr. 2024. , 2008 -
APA
Mori, R. C. T., & Machado, U. F. (2008). Glimepiride improves insulin sensitivity in MSG-obese rats without aggravating the obesity. Arquivos Brasileiros de Endocrinologia e Metabologia. São Paulo: Instituto de Ciências Biomédicas, Universidade de São Paulo. -
NLM
Mori RCT, Machado UF. Glimepiride improves insulin sensitivity in MSG-obese rats without aggravating the obesity. Arquivos Brasileiros de Endocrinologia e Metabologia. 2008 ; 52[citado 2024 abr. 23 ] -
Vancouver
Mori RCT, Machado UF. Glimepiride improves insulin sensitivity in MSG-obese rats without aggravating the obesity. Arquivos Brasileiros de Endocrinologia e Metabologia. 2008 ; 52[citado 2024 abr. 23 ] - High salt diet improves insulin sensitivity in pair-weight rats by increasing the glut, independently of leptin and TNF-'arroba' levels
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