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SMS 201-995 (SMS) is a long-acting analog of somatostatin. We studied the effect of SMS (50-100 micrograms, sc, every 8 h) on serum GH in five patients with acromegaly. Serum GH decreased significantly in four of the five patients 4 h after SMS treatment. In two of the four patients, this reduction was not sustained for 7 h, but sustained reduction to normal GH concentrations did occur in the two patients who had basal serum GH levels below 15 ng/ml. In the two patients whose responses were not sustained for 7 h, a higher dose of SMS did not cause sustained reduction in GH. SMS was well tolerated, except for one episode of elevated serum aminotransferase levels. These results indicate that SMS-induced reductions in serum GH in patients with acromegaly are often not sustained despite SMS administration every 8 h and indicate that the insufficient duration of effect may limit its therapeutic efficacy.

The syndrome of type A insulin resistance in nonobese women is characterized by hyperinsulinemia, resistance to exogenous insulin, acanthosis nigricans, polycystic ovaries, and masculinization. Insulin binding to intact circulating monocytes and cultured Epstein-Barr virus-transformed B-lymphocytes derived from these patients is decreased in some patients but normal in others. Insulin receptors consist of two subunits; the alpha-subunit contains the insulin-binding site, and the beta-subunit possesses an insulin-sensitive tyrosine-specific protein kinase activity. Insulin binding to circulating monocytes was decreased in five patients, suggesting a decreased number of alpha-subunits on the surface of cells from the patients with type A insulin resistance. In the present work, we demonstrated that there is a proportional decrease in the function of the beta-subunit (i.e. tyrosine kinase activity) in cells from these subjects. In one patient, insulin binding to circulating monocytes was normal, and the insulin-stimulated tyrosine kinase activity of the receptors was normal as well. In separate studies, using cultured Epstein-Barr virus-transformed lymphocytes from the same six patients with type A extreme insulin resistance, the results were similar, in that the functions of the alpha- and beta-subunits of the receptor from these cells correlated. Though heterogeneity among the six patients with type A extreme insulin resistance at the level of the kinase activity of their insulin receptors was demonstrated, it does not appear that a selective defect in beta-subunit phosphorylation per se can be implicated in the mechanisms of insulin resistance of these patients. These findings are distinct from our previously reported patient with normal binding and very low insulin-stimulated phosphorylation of the beta-subunit of the receptor of circulating monocytes, in whom it was speculated that selective reduction in beta-subunit phosphorylation was responsible for insulin resistance.