Bradykinin inhibits hepatic gluconeogenesis in obese mice.

摘要: The kallikrein-kinin system (KKS) has been previously linked to glucose homeostasis. In isolated muscle or fat cells, acute bradykinin (BK) stimulation was shown improve insulin action and increase uptake by promoting transporter 4 translocation plasma membrane. However, the role for BK in pathophysiology of obesity type 2 diabetes remains largely unknown. To address this, we generated genetically obese mice (ob/ob) lacking B2 receptor (obB2KO). Despite similar body weight accumulation, obB2KO showed increased fasting glycemia (162.3 ± 28.2 mg/dl vs 85.3 13.3 mg/dl), hyperinsulinemia (7.71 1.75 ng/ml 4.09 0.51 ng/ml) impaired tolerance when compared with ob/ob control (obWT), indicating resistance This corroborated production response a pyruvate challenge. Increased gluconeogenesis accompanied hepatic mRNA expression forkhead box protein O1 (FoxO1, four-fold), peroxisome proliferator-activated gamma co-activator 1-alpha (seven-fold), phosphoenolpyruvate carboxykinase (PEPCK, three-fold) glucose-6-phosphatase (eight-fold). FoxO1 nuclear exclusion also impaired, as levels this transcription factor nucleus fraction liver homogenates during random feeding. Intraportal injection lean able decrease PEPCK. conclusion, modulates homeostasis affecting obWT. These results point protective KKS mellitus.