Intermediate rather than high doses of insulin specifically improve hepatic insulin action and decrease gluconeogenic enzymes gene expression in diabetic rats (2010)
- Authors:
- Autor USP: MACHADO, UBIRATAN FABRES - ICB
- Unidade: ICB
- Assunto: FISIOLOGIA
- Language: Inglês
- Abstract: OBJETIVOS: Considering that peripheral hyperinsulinemia is observed in insulin diabetes type 1, we hipothesize that tight glycemic control by using high doses of insulin might induce insulin resistance. The present study investigated in diabetic rats the effect of different doses of insulin on hepatic sensitivity, as well as potential involved molecular mechanisms. MÉTODO E RESULTADOS: Three month-old rats were rendered diabetic by injection of alloxan (38mg/kg b.w.). Two weeks later they were submitted to treatment with saline (DS) or NPH insulin in different daily doses 1.5U (I1.5), 3U (I3), 6U (I6) and 9U (I9) for 7 Days. Non Diabetic Rats (ND) were studied as a control group. We analyzed: A) Basal glycemia; B) Liver insulin signaling; C)Foxo-1 protein subcellular distribution; D)Glucenogenic enzymes gene expressions: PEPCK (phosphoenolpyruvate Carboxykinase) and G6pase (glucose-6-phosphatase). A)Basal glycemia: As expected, DS rats were markedly hyperglycemic (p<0,001 vs ND). I3 reduced basal Glycemia (~34%, P<0.05) without bringing it back to ND values (p<0.05 vs ND). I6 And I9 restored the basal glycemia to values similar to that found in ND rats (I6 ~61%, I9 ~71%, P<0.01 vs DS)B)Liver insulin signaling analysis: I3-treated rats showed increased basal values of phosphorylated-(p)-IRbeta(~100%, P<0.01) and P-Akt Ser (~35%, P<0.05 Vs I6 And I9). C)Subcellular distribution analysis of Foxo-1: Akt is translocated to the nucleus after insulin treatment where it can phosphorylate Foxo-1. Phosphorylation of Foxo-1 leads to nuclear exclusion and inhibition of Foxo1-dependent transcription of G6pase and PEPCK, which are rate limiting enzymes for gluconeogenesis. DS decreased cytosol content of Foxo-1 DS (~39%, P<0. 001 Vs ND). I3 increased cytosol Foxo-1 content(~72%, P<0.001 vs DS, I1.5, I6 and I9. D) Gluconeogenic enzymes gene expressions: I3 reduced PEPCK (p<0.05 vs DS, I1.5, I6 and I9) and G6pase (p<0.05 Vs DS, I1.5, I6 And I9) gene expressions. I6 and I9 overexpressed these genes: PEPCK (~169% vs ND, ~46% vs DS) and G6pase (~190% vs ND, ~53% vs DS, P<0.05). CONCLUSÃO: Intermediary insulin dose (I3) improved liver insulin sensitivity rather than high doses of insulin (I6 And I9) by supressing PEPCK and G6pase gene expressions
- Imprenta:
- Source:
- Título do periódico: Resumos
- Conference titles: Reunião Anual da Federação de Sociedades de Biologia Experimental
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ABNT
OKAMOTO, M. M. et al. Intermediate rather than high doses of insulin specifically improve hepatic insulin action and decrease gluconeogenic enzymes gene expression in diabetic rats. 2010, Anais.. São Paulo: FeSBE, 2010. . Acesso em: 24 abr. 2024. -
APA
Okamoto, M. M., Sabino, R., Ferreira, M., Freitas, H. S., Mori, R. C., & Machado, U. F. (2010). Intermediate rather than high doses of insulin specifically improve hepatic insulin action and decrease gluconeogenic enzymes gene expression in diabetic rats. In Resumos. São Paulo: FeSBE. -
NLM
Okamoto MM, Sabino R, Ferreira M, Freitas HS, Mori RC, Machado UF. Intermediate rather than high doses of insulin specifically improve hepatic insulin action and decrease gluconeogenic enzymes gene expression in diabetic rats. Resumos. 2010 ;[citado 2024 abr. 24 ] -
Vancouver
Okamoto MM, Sabino R, Ferreira M, Freitas HS, Mori RC, Machado UF. Intermediate rather than high doses of insulin specifically improve hepatic insulin action and decrease gluconeogenic enzymes gene expression in diabetic rats. Resumos. 2010 ;[citado 2024 abr. 24 ] - 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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