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Despite intensive study the locus of action of tolbutamide on.carbohydrate metabolism in man is unknown. Evidence obtained by direct infusions into the pancreas in animals strongly suggests that the drug stimulates the secretion or release of insulin by the fl cells. On the other hand, there is equally strong evidence to indicate that some metabolic effects of tolbutamide are different from those observed following subcutaneous or intravenous injection of insulin. The present report describes differences in fructose and glucose metabolism in diabetic patients given tolbutamide and insulin. Subjects and MethodsDiabetic patients were divided into four groups: (1) "obese" diabetes ("adult," nonketotic, noncatabolic) ; (2) "thin" diabetes ("juvenile," ketotic, catabolic) ; ( 3 ) "steroid" diabetes (due to hyperfunction of the pituitaryadrenal system); and (4) "pancreatic" diabetes (due to destruction of the pancreas by surgery or disease).The techniques and methods used have been described previous1y.l. Each patient was admitted to the metabolic ward. Insulin injections were stopped, and studies were delayed until his metabolism had reverted to its abnormal untreated state. Tolbutamide response tests were begun after a fourteen-hour overnight fast, unless otherwise indicated. Three to five grams of tolbutamide were given by mouth, followed by venous blood sampling at hourly intervals for eight hours. In each case on a different day exactly similar observations were made without giving tolbutamide.In the second group of experiments a steady absorptive state was maintained by continuous tube feeding.? A nutritionally balanced synthetic liquid diet containing glucose or fructose as the sole carbohydrate was delivered through a tube into the gastrointestinal tract a t a constant rate day and night. ResultsIn both the "obese" and "steroid" groups of diabetic patients tolbutamide uniformly produced a decrease in the level of glucose in the blood. In the "thin" and in the "pancreatic" groups of diabetic patients i t had no effect. Tolbutamide therefore caused a response only in those diabetic patients whose plasma contains measurable amounts of i n~u l i n .~ Typical

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