IGF-1-dependent Protective Mechanisms under Hypoxia and Experimental Diabetes

The insulin-like growth factor IGF-1 may act as an insulin-independent stimulator for glucose transport and fatty acid oxidation. The components of insulin-like growth factor system are hypoxia-inducible, but the peculiarities of their hypoxic regulation have not been sufficiently investigated. The purpose of the work was to evaluate the induction of myocardial IGF-1 protein during adaptation to the effect of mild and periodic hypoxia in intact rats and in experimental diabetes. Materials and methods. The male Wistar rats, intact and with streptotrozotocin-induced diabetes, were subjects to a three-week adaptation to the middle altitude hypoxia (2100 m above sea level). A half of the rats in each group were additionally subjects to 2 weeks of periodic hypoxia séances (combined regimen, 5600 m, 1 h every 3 d). We determined the protein expression by immunoblotting. Results. The results of the study showed that a significant increase of IGF-1 protein expression in myocardium of diabetic rats were in middle altitude. This was accompanied by a decrease in hyperglycemia by 33%. Combined hypoxic treatment resulted in transient induction of the IGF-1 protein in both control and diabetic rats, more significantly in the right ventricle of the heart. The excessive induction of protein was limited. Conclusions. However, we identified the pathophysiological risks associated with the level of IGF-1. In particular, over-stimulation of IGF-1R with prolonged hyperinsulinemia over the therapeutic level required to compensate for insulin resistance, which may increase cardiovascular risk and stimulate mitogenic IGF-1 activity on cells. It is believed that the normal level of IGF-1 may be a biomarker for metabolic control in diabetes and, in combination with HbA1c, increase the reliability of the criteria for the prevention of cardiovascular risk. In view of this, the use of hypoxia may be a promising method of additional stimulatory effects on the system IGF-1 due to endogenous regulatory mechanisms to prevent excessive activation.We noted transient intensification of IGF-1-mediated protective mechanisms in the ventricles of the heart during adaptation to combined influence of hypoxia. In experimental diabetes, we observed a favorable enhancement of IGF-1 expression in the heart ventricles after both middle altitude and periodic hypoxia.