Influence of metformin on GLUT1 gene and protein expression in rat streptozotocin diabetes mellitus model

Abstract

Context: 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 streptozotocin model of diabetes mellitus.

Materials and methods: Streptozotocin-induced rats were treated with metformin while monitoring parameters of carbohydrate and lipid metabolism. GLUT1 mRNA and protein expression in kidneys, heart, liver and muscles were studied by means of real time quantitative RT-PCR and immunohistochemistry correspondingly.

Results: Metformin treatment decreased glucose concentration, glycated haemoglobin % and improved glucose tolerance. Streptozotocin diabetes provoked increase of both GLUT1 gene and protein expression in kidneys, metformin treatment produced normalization of the GLUT1 expression levels. In the liver, diabetes triggered an increase in GLUT1 protein expression, which was normalized by metformin.

Conclusion: Metformin is prospective for treatment of diabetic nephropathy.

Keywords::

• Experimental
• glycaemia
• glycated haemoglobin
• glucose transport
• anti diabetic

Acknowledgements

This study was a part of a market-oriented project ‘Influence of mildronate on carbohydrate metabolism and its regulating mechanisms in the rat experimental diabetes models’ supported by Ministry of Education of Republic of Latvia and the Joint Stock Company Grindeks of Riga, Latvia. We thank Dr. I. Stonans and Ms. D. Borovikova (JSC Grindeks, Riga) for helpful discussion of the results.

Declaration of interest

The authors confirm that data included in this manuscript cannot cause any potential conflict of interest. This study was funded from a market-oriented project Nr 08_05 ‘Influence of mildronate on carbohydrate metabolism and its regulating mechanisms in the rat experimental diabetes models’ supported by Ministry of Education of Republic of Latvia and the Joint Stock Company Grindeks of Riga, Latvia.