The effect of metformin and lipoic acid on glycogen reserves of denervated and diabetic rat muscles

Abstract

Insulin elicits subsequent biological responses by binding to its cell surface receptor. The insulin receptor has a citosolic substrate that is required for insulin to elicit subsequent biological signalling. Studies of target tissue of patients with noninsulin-dependent diabetes mellitus reported a decreased response to insulin compared to normal individuals. Studies in various cell types including adipocyte, muscle and liver have shown that there is a decrease in the receptor activities in various insulin-resistance states. Many works suggested that therapeutic concentrations of the antidiabetic metformin (MET) stimulates insulin receptor substrate activity. Direct activation of the insulin receptor tyrosine kinase by MET may be important in resistance states of diabetes, since that is relative clinical efficacy of this drug in stimulating insulin receptor. Recent studies have suggested that thioctic acid (TA), an antioxidant substance used in the treatment of diabetes, also has a peripheral effect that improves glucose transport and metabolism. In the present study, the metabolic effects of TA (0.1 mg.ml-1and MET (1.4 mg.ml-1) were evaluated in insulin resistance induced by diabetes and muscle denervation. We observed that both denervation and diabetes reduced muscle glycogen (GLY) content soleus 60% and gastrocnemius 40% in. So and MET respectively induced an elevation in GLY reserves soleus 297% and gastrocnemius 393%. In muscle of diabetic rats we observed reduction in GLY soleus 50% and gastrocnemius 24%, however, in these muscles MET induced an elevation of GLY soleus 84% and gastrocnemius 44%. TA also induced a signicative increase of GLY content in diabetic muscle soleus 573% and gastrocnemius 296%. TA treatment did not have effect in normal and denervated muscle glycogen content. This study shows that administration of metformin is able to restore glycogen synthesis in denervated muscle and suggests that this biguanide may have potential therapeutic value to restore the metabolism of denervated muscle. However, TA is unlikely to be of therapeutic benefit in denervated muscle. This date suggests that, insulin resistance state in diabetes differ of the insulin resistance observed in denervated muscle.