Metabolic effects of acarbose in normal and diabetic rats: long- and short-term administration.

The effects of acarbose administration to normal and streptozotocin-diabetic rats were studied in animals given the drug for 3 or 21 days. The acarbose was incorporated into control diets or diets fortified with sucrose and starch. After extirpating the hearts, they were perfused by the Langendorff procedure and ventricular rate and isometric force of contraction were recorded in the presence or absence of isoproterenol. Frozen samples of heart and liver were used for metabolic measurements. At a low dose of isoproterenol (0.01 microgram) the positive inotropic response was the same in control and diabetic animals. With a higher dose of the amine (0.1 microgram) the contractile response was increased further in hearts from normal animals but not enhanced in hearts from diabetic rats. Cardiac phosphorylase activation by isoproterenol was accentuated by diabetes only when the smaller dose of the amine was given. The markedly elevated heart glycogen content of diabetic rats was decreased in response to a high carbohydrate diet. Inclusion of acarbose in the diet prevented this diminution in cardiac glycogen. In normal and diabetic rats fed the high carbohydrate diet for 3 weeks, liver glycogen was elevated. The increase in hepatic glycogen was not observed when acarbose was present in the diet. A comparison of the results of the short- and long term-administration of acarbose show that the onset of action of the drug is prompt and that the effect of the treatment is undiminished over an extended period of time.