Carbohydrate metabolism and lipid storage and breakdown in diabetes.

Abstract

Interactions between the metabolism of glucose and lipids provide the basis for a number of metabolic disturbances which have been observed in clinical and experimental diabetes. Particular examples are abnormalities which may be seen in the storage and mobilisation of lipid and in the relative contribution of glucose and fatty acid to energy needs. The concept of a Glucose Fatty Acid Cycle is reviewed and forms the basis for recent studies which are outlined. An essential feature of the Cycle is the proposal that the normal relationship between glucose and fatty acid metabolism is reciprocal and not dependent; and that the augmented release of fatty acids for oxidation in muscle and other tissues in diabetes is not primarily due to defective glucose metabolism. The release and oxidation of fatty acids may depend upon lipolysis which may be directly regulated by hormone action and not dependent upon glucose metabolism. It can also depend upon esterification of fatty acids which may involve the metabolism of glucose to glycerol phosphate. Evidence is presented that lipid mobilization in the alloxan-diabetic rat which may be insensitive to inhibition by insulin action is primarily dependent upon activation of lipolysis. Although the concentration of glycerol phosphate is diminished in muscle in this form of diabetes this is not a consequence of diminished glucose uptake and it is moreover associated with an increased rate of esterification of fatty acids. In adipose tissue the concentration of glycerol phosphate is not reduced, even though glucose uptake is diminished, and the rate of esterification of fatty acid is accelerated. The concentration of triglyceride in muscle is increased in alloxan-diabetes in the rat and this may be attributed to increased mobilisation of fatty acids from adipose tissue associated with increased esterification to triglyceride in muscle. An increased rate of glucose uptake may be an important factor leading to triglyceride storage in adipose tissue and possibly in muscle when insulin acts on these tissues in the normal animal. The evidence for the possibility that lipid mobilisation may have consequential effects on carbohydrate metabolism and insulin sensitivity in alloxan-diabetes has been briefly reviewed and suggestions made for future studies. It is suggested that our understanding of the mechanisms which may control insulin sensitivity is incomplete, and as a consequence the quantitative importance of the contributions which fatty acid oxidation may make to insulin insensitivity in diabetes remains to be established.