Walter Puls

Inhibition of sucrase by tris in rat and man, demonstrated by oral loading tests with sucrose

In the course of work concerned with the inhibition of small intestinal carbohydrate digesting enzymes, experiments were performed on rats and two healthy volunteers using tris as a sucrase inhibitor. The following results were obtained: (1) Tris does not lower the blood glucose in fasting rats after oral or subcutaneous doses up to 500 mg/kg, when administered as neutral solution (pH 7.0). (2) Tris reduces reduces the glycemia in rats and human subjects after a sucrose load. In addition, the insulinemia caused by administration of sucrose is reduced in man. This smoothing effect on both curves is dose-dependent. A delay of gastric emptying by tris could be excluded. (3) After a glucose or matose load in rats, tris has no effect on the blood sugar curve. (4) The marked smoothing effect of tris is after sucrose loading is probably caused by its well-known in vitro inhibitory effect on intestinal sucrase activity of pigs and humans.

Inhibition of Disaccharide Digestion in Rat Intestine by the α-Glucosidase Inhibitor Acarbose (BAY g 5421)

Administration of the alpha-glucosidase inhibitor, acarbose (BAY g 5421), to rats together with a sucrose load results in a marked retardation of sucrose digestion. The carbohydrate content of the small intestine is dose dependently increased; the time needed for the absorption is doubled. In the large intestine significant amounts of carbohydrate can be found only after administration of high doses of acarbose (2-4 mg/kg p.o.). In oral sucrose and maltose loading tests the blood glucose increase is dose dependently reduced by acarbose (ED50, 1 or 12 mg/kg, respectively). In perfused jejunal loops of rats, acarbose inhibits the absorption of sucrose (4 g/l) and maltose (1 and 2 g/l), the IC50 values being 3.2, 36, and 57 micrograms/ml, respectively. The data indicate that acarbose effectively inhibits sucrose digestion. It is 10-20 times less effective with maltose as a substrate. Slight malabsorption is induced by acarbose only in doses higher than the ED50.

The effects of meal feeding on the incorporation of D-[U-14C]-glucose into tissue lipids and glycogen as a function of increasing intravenous glucose dose.

Abstract The in vivo incorporation of D-[U-14C]-glucose into lipids and glycogen of adipose tissues, muscle tissues, and liver was measured 1 hr after the i.v. injection of increasing glucose doses (0.75, 1.5 and 2.5 g glucose/kg of body weight) in meal-fed and ad libitum-fed rats. In both perirenal and epididymal fat tissue, the levels of 14C-label in the total lipid extract was significantly higher in meal-fed than in nibbling rats at all glucose doses. As the glucose dose increased, the 14C-label in the lipids of both adipose tissues in meal-fed rats increased more than would be expected, assuming a linear dose dependency. In adipose tissues of nibbling rats, glucose dose dependency was linear. The 14C radioactivity in heart muscle lipids was significantly higher in meal-fed rats at all three glucose doses. In the diaphragm, this effect was seen only at the two higher doses; in liver, only at the highest dose; in skeletal muscle, there was no difference at any of the dose levels. The incorporation of 14C-label into tissue glycogen exhibited an entirely different pattern. Muscle glycogen synthesis tended to reach a plateau at the middle glucose dose in meal-fed rats, whereas it increased sharply with increasing glucose dose in nibbling rats. Indeed, muscle glycogen synthesis was much greater in nibbling rats than would be expected, assuming linear dose dependency. It was concluded that the two groups of rats responded quite differently to the increasing glucose load. The excess glucose tended to be incorporated into lipid in meal-fed rats and to muscle glycogen in nibbling rats.

Drug concentration monitoring, microbial alpha-glucosidase inhibitors, plasminogen activators

Drug Concentration Monitoring.- Microbial Alpha-Glucosidase Inhibitors: Chemistry, Biochemistry and Therapeutic Potential.- Plasminogen Activators: Molecular Properties, Biological Cell Function and Clinical Application.- Author Index Volumes 1-7.

Pharmacological Characterization of Bay G 5421, A Glucosidase Inhibitor for the Treatment of Carbohydrate-Dependent Metabolic Disorders

BAY g 5421* delays starch as well as sucrose digestion in the small intestine by inhibiting glucosidases involved in the hydrolysis of oligosaccharides. As a consequence in loading tests with both carbohydrates the blood glucose and serum insulin increments are reduced in animals and in man. The ED 50 is approximately 0.5–3 mg BAY g 5421/kg per os.