SKELETAL-MUSCLE PROTEIN-TYROSINE-PHOSPHATASE ACTIVITY AND TYROSINE PHOSPHATASE1B PROTEIN-CONTENT ARE ASSOCIATED WITH INSULIN ACTION AND RESISTANCE

Particulate and cytosolic protein tyrosine phosphatase (PTPase) activi ty was measured in skeletal muscle from 15 insulin-sensitive subjects and 5 insulin-resistant nondiabetic subjects, as well as 18 subjects w ith non-insulin-dependent diabetes mellitus (NIDDM). Approximately 90% of total PTPase activity resided in the particulate fraction. In comp arison with lean nondiabetic subjects, particulate PTPase activity was reduced 21% (P < 0.05) and 22% (P < 0.005) in obese nondiabetic and N IDDM subjects, respectively. PTPase1B protein levels were like,,ise de creased by 38% in NIDDM subjects (P < 0.05). During hyperinsulinemic g lucose clamps, glucose disposal rates (GDR) increased approximately si xfold in lean control and twofold in NIDDM subjects, while particulate PTPase activity did not change. However, a strong positive correlatio n (r = 0.64, P < 0.001) existed between particulate PTPase activity an d insulin-stimulated GDR. In five obese NIDDM subjects, weight loss of similar to 10% body fft resulted in a significant and corresponding i ncrease in both particulate PTPase activity and insulin-stimulated GDR . These findings indicate that skeletal muscle particulate PTPase acti vity and PTPase1B protein content reflect in vivo insulin sensitivity and are reduced in insulin resistant states. We conclude that skeletal muscle PTPase activity is involved in the chronic, but not acute regu lation of insulin action, and that the decreased enzyme activity may h ave a role in the insulin resistance of obesity and NIDDM.