Dissection of the metabolic actions of insulin in adipocytes from early growth-retarded male rats

Numerous studies have shown a relationship between early growth restriction and Type 2 diabetes. Studies have shown that offspring of rats fed a low p rotein (LP) diet during pregnancy and lactation have a worse glucose tolera nce in late adult life compared with controls. In contrast, in young adult life LP offspring have a better glucose tolerance which is associated with increased insulin-stimulated glucose uptake into skeletal muscle. The aim o f the present study was to compare the regulation of glucose uptake and lip olysis in adipocytes by insulin in control and LP offspring. LP adipocytes had increased basal and insulin-stimulated glucose uptake compared with con trols. There was no difference in basal rates of lipolysis. Isoproterenol s timulated lipolysis in both groups, but it was more effective on LP adipocy tes. Insulin reduced lipolytic rates in controls to basal levels but had a reduced effect in LP adipocytes. Protein kinase B activity matched glucose uptake, with LP adipocytes having elevated activities. These results sugges t that early growth retardation has long-term effects on adipocyte metaboli sm. In addition, they show selective resistance to different metabolic acti ons of insulin and provide insight into the mechanisms by which insulin reg ulates glucose uptake and lipolysis.