Laboratório de Enzimologia e Controle do Metabolismo-LabECoM, Faculdade de Farmácia, UFRJ, Brazil.
Arch Biochem Biophys. 2010 Apr 1;496(1):53-60. doi: 10.1016/j.abb.2010.01.013. Epub 2010 Feb 1.
The present work describes the effects of metformin on hexokinase (HK) and phosphofructokinase (PFK) activities and localization in different tissues from streptozotocin-induced diabetic mice. Diabetic mice present lower HK and PFK activities (50%) in skeletal muscle, liver and adipose tissue, as compared with control (P<0.05). Treatment with 250 mg/kg metformin reverses this pattern of enzyme inhibition with concomitant reversal of hyperglycemia and hypolactacidemia. Furthermore, the treatment increases the cytoskeleton-associated PFK activity in skeletal muscle; this activity has been described as an important mechanism for the enzyme activation. This effect might be due to the increased phosphorylation of serine residues in the enzyme, a modification which has been described to increase the interaction of PFK with f-actin. The current work supports the hypothesis that metformin hypoglycemic effects involve the activation of glycolysis through its regulatory enzymes, which may be potential targets for the development of new hypoglycemic drugs.
本研究描述了二甲双胍对链脲佐菌素诱导的糖尿病小鼠不同组织中己糖激酶（HK）和磷酸果糖激酶（PFK）活性和定位的影响。与对照组相比，糖尿病小鼠的骨骼肌、肝脏和脂肪组织中的 HK 和 PFK 活性（50%）降低（P<0.05）。用 250mg/kg 的二甲双胍治疗可逆转这种酶抑制模式，并伴有高血糖和低乳酸血症的逆转。此外，该治疗增加了骨骼肌中与细胞骨架相关的 PFK 活性；这种活性被描述为酶激活的重要机制。这种效应可能是由于酶的丝氨酸残基磷酸化增加所致，这种修饰已被描述为增加 PFK 与 f-肌动蛋白的相互作用。目前的研究支持这样一种假设，即二甲双胍的降血糖作用涉及通过其调节酶激活糖酵解，这可能是开发新的降血糖药物的潜在靶点。
