MECHANISMS MODIFYING GLUCOSE-OXIDATION IN DIABETES-MELLITUS

The Glucose Fatty Acid Cycle as formulated 30 years ago and reviewed i n the Minkowski lecture in 1966 described short term effects of fatty acids (minutes) to decrease uptake, glycolysis and oxidation of glucos e in heart and skeletal muscles. Such short term effects have since be en extended to include inhibition of glucose uptake and glycolysis and stimulation of gluconeogenesis in liver and these effects have also b een convincingly demonstrated in man in vivo. More recently a longer t erm effect of fatty acid metabolism to decrease glucose oxidation (hou rs) has been shown in heart and skeletal muscle and Liver. This effect increases the specific activity of pyruvate dehydrogenase kinase, whi ch in turn results in enhanced phosphorylation and inactivation of the pyruvate dehydrogenase complex. Activity of the pyruvate dehydrogenas e complex is the major determinant of glucose oxidation rate. It seems likely that longer term effects of fatty acids on this and other aspe cts of glucose metabolism could be important in the development of ins ulin resistance in diabetes mellitus in man.