Introduction: Metformin improves hyperglycaemia via mechanisms which include activation of AMP-activated protein kinase (AMPK). Recent findings indicate that some metabolic actions of metformin occur also by AMPK-independent mechanisms.
Objective: To study the action of metformin on expression of GLUT1 glucose transporter in rat models of severe and mild stretozotocin diabetes mellitus.
Materials and methods: Severe diabetes mellitus in rats was induced by single injection of streptozotocin 50 mg/kg, i.v. To induce mild diabetes mellitus with hyperlipidaemia, rats were fed by high-fat chaw for 2 weeks, then two i.p. injections of streptozotocin (35 and 30 mg/kg) followed with a week interval. Rats were treated with metformin (100 mg/kg daily, per os) for 6 weeks while monitoring parameters of carbohydrate and lipid metabolism. GLUT1 mRNA and protein expression in kidneys, heart and liver were studied by means of real time RT-PCR and immunohistochemistry correspondingly.
Results: In severely diabetic rats, metformin treatment decreased glucose concentration, glycated haemoglobin % and improved glucose tolerance. In mildly diabetic rats, only decrease in glycated haemoglobin % was observed in the end of the metformin treatment. Streptozotocin diabetes provoked increase of both GLUT1 gene and protein expression in kidneys of both severely and mildly diabetic rats. Metformin treatment produced normalization of the GLUT1 gene and protein expression levels in severely diabetic rats, in mildly diabetic rats only GLUT1 protein expression was normalized. In the liver, severe (but not mild) diabetes triggered an increase in GLUT1 protein expression, which was normalized by metformin. GLUT1 protein expression was increased in the hearts of severely and mildly diabetic rats. Metformin normalized the parameter only in severely diabetic rats.
Conclusion: Metformin decreases GLUT1 hyperexpression in kidneys, induced by streptozotocin severe diabetes mellitus and mild diabetes mellitus with hyperlipidaemia. Therefore, it is prospective for treatment of diabetic nephropathy.
30 Apr - 04 May 2011
European Society of Endocrinology