ALTERED BASAL AND INSULIN-STIMULATED PHOSPHOTYROSINE PHOSPHATASE (PTPASE) ACTIVITY IN SKELETAL-MUSCLE FROM NIDDM PATIENTS COMPARED WITH CONTROL SUBJECTS

To measure possible changes in basal and insulin-stimulated phosphotyr osine phosphatase (PTPase) activity in skeletal muscle from insulin-re sistant individuals, soluble and particulate muscle fractions were pre pared from biopsies taken before and after a 3-h hyperinsulinaemic eug lycaemic clamp in eight non-insulin-dependent: diabetic (NIDDM) patien ts and nine control subjects. We used a sensitive sandwich-immunofluor escence assay and the human insulin receptor as the substrate, PTPase activity was expressed as percentage of dephosphorylation of phosphoty rosyl-residues in immobilized insulin receptors per 2 h incubation tim e per 83 mu g and 19 mu g muscle fraction protein (soluble and particu late fraction, respectively). In the diabetic soluble muscle fractions , the basal PTPase activity was decreased compared with that of contro l subjects (11.5 +/- 5.5 vs 27.5 +/- 3.3, p < 0.04, mean +/- SEM). In the particulate muscle fractions from the control subjects, PTPase act ivity was increased after 3 h hyperinsulinaemia (20.0 +/- 3.2 vs 30.2 +/- 3.6, p < 0.03) and in the corresponding soluble fractions PTPase a ctivity seemed decreased (27.5 +/- 3.3 vs 19.9 +/- 5.9, NS). No effect of insulin on PTPase activity was found in NIDDM patients (25.1 +/- 4 .1 vs 27.2 +/- 5.2, 11.5 +/- 5.5 vs 15.1 +/- 4.5 [particulate and solu ble fractions], NS). In conclusion, we found that the basal PTPase act ivity in soluble muscle fractions was decreased in NIDDM patients; fur thermore, insulin stimulation was unable to increase PTPase activities in the particulate fractions, as opposed to the effect of insulin in control subjects.