Alterações no metabolismo da glicose em dois modelos experimentais de obesidade

Abstract

The kallikrein-kinin system (KKS) is involved in several biological processes such as pain modulation, vasodilation, vascular permeability, edema, inflammation, and glucose homeostasis, and its effects mediated by two specific G protein coupled receptors, the B1 and B2 receptor of kinins. The aim of the present study is to investigate the participation of the B1 (B1R) receptor of kinins in metabolic processes related to obesity in obese mice. Leptin-deficient mice and kinase B1R knockouts (obB1) were used for this. The results showed that obB1 animals presented a reduction in food intake in all evaluated period (4th to 26th week of life), (obWT: 63.79 ± 1.59; obB1: 51.22 ± 1.09 g; P<0.001) at 6 months of age (obWT: 74.61 ± 1.04; obB1: 57.98 ± 1.58 g; P<0.001) and lower fat deposition. In the glucose tolerance test, obB1 animals presented higher glucose uptake than their controls when young (obWT: 46045 ± 3492; obB1: 30875 ± 2311 mg/dL/min; P<0.01). An increase in insulin resistance in the insulin sensitivity test and a poor gluconeogenesis capacity in the pyruvate challenge at 3 months of age were observed, with this parameter disappearing in older animals. Isolated islets of knockout animals had a greater ability to secrete insulin at 3 months of age. In older animals the controls increase this capacity by matching knockouts. In addition, increased liver weight was observed in these animals, when older (obWT: 3.29 ± 0.24; obB1 4.09 ± 0.06 g; P<0.001). These results suggest that kin receptor B1 deficiency in the model of mice with severe obesity reduces obesity and may be beneficial in protecting against related diseases at first. Animals with middle age, however, present aggravation of glucose metabolism and liver injury.