Beta-adrenoceptors desensitization may modulate catecholamine induced insulin resistance in human pheochromocytoma.
Catecholamines acutely exert a pronounced insulin-antagonistic effect, which is mediated by beta-adrenergic receptors stimulation. Nevertheless, several patients with pheochromocytoma fail to exhibit an overt diabetic syndrome, in spite of steadily elevated plasma levels of catecholamines. This prompted us to investigate a 16 years old male patient, bearing an extra-adrenal pheochromocytoma, who displayed a slightly impaired glucose tolerance to oral glucose tolerance test, whereas fasting and post-prandial blood glucose, as well as glycaemic response to intravenous glucagon, were in the normal range. Peripheral insulin sensitivity, as evaluated by intravenous insulin tolerance test, was slightly decreased. Supine norepinephrine plasma levels were steadily upon 9 ng/ml; plasma insulin, both fasting and post-prandial, was within the normal range. beta-adrenergic receptors density of peripheral mononuclear cells was strongly reduced when compared to controls (0.97 +/- 0.08 vs 2.82 +/- 0.37 fmol/10(6) cells), without any concomitant change of affinity. Insulin binding to circulating monocytes was reduced as well (2.38 +/- 0.27 vs 5.1 +/- 0.4%/10(7) monocytes); insulin receptor affinity was quite normal (1.7 ng/ml) and total receptor number was 9,200 sites/cell. In desensitization experiments, 1 microM isoproterenol caused only a 20% decrease of beta-adrenergic receptors density in the patient's cells (70% decrease in controls). Six months after surgery, all the above modifications of receptor binding, as well as the mild glucose intolerance, were almost completely reversed. Thus, high levels of norepinephrine were able to induce a decrease of both beta-adrenoceptor and insulin receptor binding, together with a marked reduction of in vitro agonist-induced redistribution of beta-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
di Paolo
S
S
Clinica Medica III, Università di Bari, Italy.
de Pergola
G
G
Cospite
M R
MR
Guastamacchia
E
E
Cignarelli
M
M
Balice
A
A
Cospite
M R
MR
Nardelli
G M
GM
Giorgino
R
R
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000097:blood / Q000503:physiopathology* / Q000601:surgery; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002395:Catecholamines / Q000097:blood*; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D010673:Pheochromocytoma / Q000097:blood / Q000503:physiopathology* / Q000601:surgery; D011972:Receptor, Insulin / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D011972:Receptor, Insulin; D007545:Isoproterenol