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 alpha 2-adrenoceptor-mediated antilipolytic effect of catecholamines was normal, but the beta-adrenoceptor-mediated lipolytic sensitivity was increased 10-fold (P less than .01) in diabetic subjects before and after exercise. The latter correlated inversely (r greater than .7) with the circulating norepinephrine level, which was significantly reduced in diabetic subjects. Basal lipolysis and lipolysis activated at different steps distal to the beta-receptor were similar in the two groups. There was no major change in the total number of beta- and alpha-adrenoceptors in the diabetic patients. However, the proportion of high-affinity beta-adrenoceptors was significantly increased in these patients compared with control subjects. In the diabetic patients, approximately 50% of the beta-adrenoceptors were in a high-affinity state, compared to approximately 30% in the control subjects (P less than .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) beta-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.
Wahrenberg
H
H
Department of Medicine, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden.
Lönnqvist
F
F
Engfeldt
P
P
Arner
P
P
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D004837:Epinephrine / Q000097:blood; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D012016:Reference Values; D015016:Yohimbine / Q000494:pharmacology
D007328:Insulin; D015016:Yohimbine; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine