GdCl3 reduces hyperglycaemia through Akt/FoxO1-induced suppression of hepatic gluconeogenesis in Type 2 diabetic mice

GdCl3 (gadoliniumchloride) can reduce blood glucose, however, the underlying mechanism remains unclear. Liver gluconeogenesis is an important pathway involved in the maintenance of glucose homeostasis. The aim of the present study was to investigate the role of GdCl3 on hepatic gluconeogenesis and explore the precisemolecular mechanism. A classical Type 2 diabetic mouse model, created by exposing C57BL/6J mice to a high fat diet for 4 months, was treated with GdCl3 or saline. Bodyweight, blood glucose, and insulin sensitivity were monitored. It was observed that GdCl3 significantly reduced blood glucose levels and improved insulin sensitivity. Pyruvate tolerance test further showed that GdCl3 could suppress gluconeogenesis ofdiabetic mice. And in the livers of GdCl3 treated-mice, the expression of Pepck (phosphoenolpyruvate carboxykinase) and G6pase (glucose-6-phosphatase), the key enzymes for gluconeogenesis exhibited an outstanding reduction. Furthermore,experiments in hepatocarcinoma cells revealed that GdCl3 could activate the Akt pathway to promote the phosphorylation of FoxO1, leading to the suppression of gluconeogenesis by reducing the expression of PEPCK and G6Pase, resulting indecreased cellular production of glucose. Comparable results were observed in the livers of GdCl3-treated mice. In addition, it was demonstrated that GdCl3 augmented the role of insulin to control hepatic glucose production. We conclude that GdCl3 reduces hyperglycaemia via Akt/FoxO1-induced s...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research