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(Reference retrieved automatically from SciELO through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Abnormal subcellular distribution of GLUT4 protein in obese and insulin-treated diabetic female dogs

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Author(s):
A.M. Vargas [1] ; R.P.A. Barros [2] ; R.A. Zampieri [3] ; M.M. Okamoto [4] ; P. de Carvalho Papa [5] ; U.F. Machado [6]
Total Authors: 6
Affiliation:
[1] Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Fisiologia e Biofísica - Brasil
[2] Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Fisiologia e Biofísica - Brasil
[3] Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Fisiologia e Biofísica - Brasil
[4] Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Fisiologia e Biofísica - Brasil
[5] Universidade de São Paulo. Faculdade de Medicina Veterinária e Zootecnia. Departamento de Cirurgia - Brasil
[6] Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Fisiologia e Biofísica - Brasil
Total Affiliations: 6
Document type: Journal article
Source: Brazilian Journal of Medical and Biological Research; v. 37, n. 7, p. 1095-1101, 2004-07-00.
Abstract

The GLUT4 transporter plays a key role in insulin-induced glucose uptake, which is impaired in insulin resistance. The objective of the present study was to investigate the tissue content and the subcellular distribution of GLUT4 protein in 4- to 12-year-old control, obese and insulin-treated diabetic mongrel female dogs (4 animals per group). The parametrial white adipose tissue was sampled and processed to obtain both plasma membrane and microsome subcellular fractions for GLUT4 analysis by Western blotting. There was no significant difference in glycemia and insulinemia between control and obese animals. Diabetic dogs showed hyperglycemia (369.9 ± 89.9 mg/dl). Compared to control, the plasma membrane GLUT4, reported per g tissue, was reduced by 55% (P < 0.01) in obese dogs, and increased by 30% (P < 0.05) in diabetic dogs, and the microsomal GLUT4 was increased by ~45% (P < 0.001) in both obese and diabetic animals. Considering the sum of GLUT4 measured in plasma membrane and microsome as total cellular GLUT4, percent GLUT4 present in plasma membrane was reduced by ~65% (P < 0.001) in obese compared to control and diabetic animals. Since insulin stimulates GLUT4 translocation to the plasma membrane, percent GLUT4 in plasma membrane was divided by the insulinemia at the time of tissue removal and was found to be reduced by 75% (P < 0.01) in obese compared to control dogs. We conclude that the insulin-stimulated translocation of GLUT4 to the cell surface is reduced in obese female dogs. This probably contributes to insulin resistance, which plays an important role in glucose homeostasis in dogs. (AU)

FAPESP's process: 02/07384-4 - Regulation of glucose transporters gene expression in Diabetes Mellitus: Pathophysiological role and potential preventive and therapeutical approaches
Grantee:Ubiratan Fabres Machado
Support Opportunities: Research Projects - Thematic Grants