Sequential Changes in Adipose Tissue Metabolism in Alloxan-Diabetic Rats

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Abstract
In order to study changes in adipose tissue metabolism which developed during insulin deficiency, alloxan-diabetic rats were maintained on daily insulin injections, which were then terminated and the resulting metabolic changes studied during the next 96 hr. The results of these experiments are reported in the present communication. Insulin deficiency of 1 to 3 hr. duration produced by injection of antibodies to insulin produces an accumulation of free fatty acids in adipose tissue and this precedes any impairment of glucose uptake or glyceride-glycerol formation by the tissue in vitro. Insulin has been shown to have a direct effect on lipolysis in adipose tissue independent of its effect on glucose metabolism. In this case insulin appears to prevent the activation of lipolysis by catecholamines and other lipolytic hormones. However, in rats which have been alloxan diabetic for several weeks, glucose uptake by adipose tissue is severely impaired. Free fatty acid release from such tissue is thought to be related to reduced re-esterification which results from a lack of [alpha]-glycerolphosphate which in turn is related to reduced glucose utilization. It would appear then that in long-standing diabetes re-esterification of fatty acids rather than increased lipolysis is the major defect in adipose tissue leading to increased free fatty acid release.