Reduced
insulin receptor tyrosine kinase activity and internalization have been reported in
non-insulin-dependent diabetes mellitus (
NIDDM) patients. To clarify whether in
NIDDM the defective internalization is caused by the defective
kinase activity, we studied
receptor tyrosine kinase activity and internalization in monocytes from eight lean control and six obese subjects and 10 obese
NIDDM patients. Receptor internalization was also stimulated by an anti-
insulin receptor antibody (MA-10) that is unable to stimulate receptor
kinase activity. Basal exogenous
tyrosine kinase activity was not different in monocytes from the three groups of subjects. As compared with control subjects (2,690 +/- 637 fmol 32P incorporated),
insulin (100 nmol/L)-stimulated
tyrosine kinase activity was lower in
NIDDM patients (1,262 +/- 318, P < .05), but not in obese subjects (2,640 +/- 731). Basal receptor autophosphorylation did not differ between the three groups, whereas
insulin-stimulated autophosphorylation in comparison to that in control subjects was reduced in
NIDDM patients (P < .05), but not in obese subjects. In
NIDDM patients, receptor internalization induced by both
insulin and MA-10, was lower (P < .05) than that in control and obese subjects. No correlation was found between receptor internalization and exogenous
tyrosine kinase activity (r = .30, NS) or autophosphorylation (r = .08, NS).(ABSTRACT TRUNCATED AT 250 WORDS)