The effect of insulin on oxidative phosphorylation in normal and diabetic mitochondria

1960 Journal of Biological Chemistry  
Several investigators have confirmed that insulin exerts a direct effect on carbohydrate oxidation in vitro. The stimulation of oxygen consumption by insulin was first shown in muscle homogenates by Krebs (1) and in intact muscle by Hall (2). Villee and Hastings (3) found pyruvate oxidation depressed in diabetic rat diaphragm and corrected by insulin. Previous work in this laboratory (4) has shown that the oxygen consumption of intact diabetic mammalian muscle is depressed and that insulin
more » ... d that insulin stimulates this in vitro in the presence or absence of substrate. Lee and Williams (5) and Lee and Wiseman (6) have demonstrated that insulin in a physiological active form becomes intimately bound to mitochondria and microsomes. Thus it seemed logical to postulate that insulin affects oxidative phosphorylation in mitochondria. Goranson and Erulkar (7) reported that phosphate utilization was decreased in the diabetic rat; but most work with mitochondrial preparations has produced negative results. Parks et al. (8) found no difference in the uptake of inorganic phosphate and oxygen consumption between mitochondria from normal and alloxan-diabetic rats and no effect of insulin added in vitro. Vester and Stadie (9) confirmed these results, but found that mitochondria from depancreatized cats had low P:O ratios which were not affected by insulin in vitro. However, these ratios were restored to normal by 3 days of insulin injection in vivo. Because of these conflicting results the oxidative phosphorylation of mitochondria from alloxan-diabetic rats and depancreatized cats and the effects of insulin thereon in vivo and in vitro have been investigated.' The results obtained have shown a clear cut defect in oxidative phosphorylation in diabetic mitochondria which is sensitive to insulin both in vivo and in V&O. EXPERIMENTAL Production of Diabetes-Alloxan diabetes in rats was induced by the subcutaneous injection of alloxan monohydrate (180 mg per kg) into male Sherman strain rats weighing 150 to 180 g. The animals were fasted 24 hours before injection and were given two doses 24 hours apart The animals were used after 2 weeks of established diabetes with blood glucose levels in excess of 300 mg per 100 ml and if pronounced polydipsia, polyurea, glycosuria, and ketonuria were present. Animals were maintained on
pmid:14399044 fatcat:gfe6sgud5nh5vfcdc7ohc2inla