Premium
Metformin reverses hexokinase and phosphofructokinase downregulation and intracellular distribution in the heart of diabetic mice
Author(s) -
Da Silva Daniel,
Ausina Priscila,
Alencar Edgard M.,
Coelho Wagner S.,
Zancan Patricia,
SolaPenna Mauro
Publication year - 2012
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1063
Subject(s) - metformin , phosphofructokinase , hexokinase , medicine , endocrinology , diabetic cardiomyopathy , diabetes mellitus , glycolysis , streptozotocin , intracellular , downregulation and upregulation , cardiomyopathy , chemistry , heart failure , metabolism , biochemistry , gene
Diabetes mellitus is characterized by hyperglycemia and its associated complications, including cardiomyopathy. Metformin, in addition to lowering blood glucose levels, provides cardioprotection for diabetic subjects. Glycolysis is essential to cardiac metabolism and its reduction may contribute to diabetic cardiomyopathy. Hexokinase (HK) and phosphofructokinase (PFK), rate‐limiting enzymes of glycolysis, are downregulated in cardiac muscle from diabetic subjects, playing a central role on the decreased glucose utilization in the heart of diabetic subjects. Thus, the aim of this study was to determine whether metformin modulates heart HK and PFK from diabetic mice. Diabetes was induced by streptozotocin injection on male Swiss mice, which were treated for three consecutive days with 250 mg/kg metformin before evaluating HK and PFK activity, expression, and intracellular distribution on the heart of these subjects. We show that metformin abrogates the downregulation of HK and PFK in the heart of streptozotocin‐induced diabetic mice. This effect is not correlated to alteration on the enzymes' transcription and expression. However, the intracellular distribution of both enzymes is altered in diabetic hearts that show increased activity of the soluble fraction when compared to the particulate fraction. Moreover, this pattern is reversed upon the treatment with metformin, which is correlated with the effects of the drug on the enzymes activity. Altogether, our results support evidences that metformin alter the intracellular localization of HK and PFK augmenting glucose utilization by diabetic hearts and, thus, conferring cardiac protection to diabetic subjects. © 2012 IUBMB IUBMB Life, 64(9): 766–774, 2012