Relationship between insulin receptor tyrosine kinase activity and internalization in monocytes of non-insulin-dependent diabetes mellitus patients.
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)
Cattedra di Endocrinologia, Università di Catania, Ospedale Garibaldi, Italy.
V
V
Trischitta
F
F
Giorgino
L
L
Frittitta
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R
Scalisi
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R
Vigneri
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*
D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin