Chronic and endogenous regulation of insulin receptors by catecholamines in adipocytes from patients with a phaeochromocytoma

Abstract

Insulin binding in adipocytes from patients with a phaeochromocytoma (PH) approached that of the controls (C) at low and higher concentrations of unlabeled insulin. The apparent receptor affinity was unchanged (ED50: PH 0.50 x 10(-9) M and C 0.60 x 10(-9) M). Scatchard analysis of the binding data using the negative cooperative model revealed a 46% decrease in the total number of receptors together with no changes in both K-e (PH 0.55 x 10(9) M-1 and C 0.36 x 10(9) M-1) and K-f (PH 0.13 x 10(9) M-1 and C 0.07 x 10(9) M-1). According to the two site model, an altered proportion in the two classes of insulin binding sites was detected. This was accompanied by a catecholamine-desensitization of the adipocytes to the antilipolytic action of insulin. These events could represent a final situation of a chronic and endogenous regulation by high levels of catecholamines of insulin receptors in human adipose tissue.

Tissue‐specific modulation of insulin receptor mRNA levels in a patient with a phaeochromocytoma

“…These findings are in partial agreement with the results of our previous studies on insulin binding in adipocytes from patients with this pathology. In those studies (Carranza et al, 1990) a decrease in the total number of insulin receptors and a catecholamine-induced desensitization of the adipocytes to the antilipolytic action of insulin were demonstrated. However, such a correlation cannot be established in the case of liver or muscle because no insulin binding and/or postbinding studies have been performed using these tissues from patients with a phaeochromocytoma.…”

“…Patients with a phaeochromocytoma represent a pathophysiological model of insulin resistance produced by chronically high catecholamine levels (Feldman, 1985). In isolated adipocytes from patients with a phaeochromocytoma, we have previously observed a decrease in the number of insulin receptors on the cell surface and an impairment in the capacity of response to the antilipolytic action of insulin (Carranza et al, 1990). We therefore studied the possible existence of changes at the level of insulin receptor (IR) mRNA in biopsies of adipose tissue, liver and skeletal muscle from a patient with a phaeochromocytoma.…”