Abnormal Action of Catecholamines on Lipolysis in Adipocytes of Type I Diabetic Patients Treated With Insulin

Catecholamine-induced lipolysis was investigated in adipocytes obtained before and after 30 min of exercise from 10 insulin-treated type I (insulin-dependent) diabetic men and 10 male matched control subjects. The α2-adrenoceptor-mediated antilipolytic effect of catecholamines was normal, but the β-adrenoceptor-mediated lipolytic sensitivity was increased 10-fold (P < .01) in diabetic subjects before and after exercise. The latter correlated inversely (r > .7) with the circulating norepinephrine level, which was significantly reduced in diabetic subjects. Basal lipolysis and lipolysis activated at different steps distal to the β-receptor were similar in the two groups. There was no major change in the total number of β- and α-adrenoceptors in the diabetic patients. However, the proportion of high-affinity β-adrenoceptors was significantly increased in these patients compared with control subjects. In the diabetic patients, ∼50% of the β-adrenoceptors were in a high-affinity state, compared to ∼30% in the control subjects (P < .025). In diabetic subjects there was an enhanced plasma glycerol response to exercise, despite a blunted plasma norepinephrine response. The data suggest enhanced sensitivity of catecholamine-induced lipolysis in type I diabetes due to an increase in the number of high-affinity (i.e., coupled) β-adrenoceptors in fat cells. This mechanism may be due to low levels of circulating norepinephrine and may also explain the exaggerated lipolytic response to exercise in the diabetic state.