Peripherally active anorectic agents represent a new approach to the pharmacological management of obesity. Two inhibitors of carbohydrate absorption: an alpha-glucosidase inhibitor, acarbose (Bay g 5421) and a alpha-amylase inhibitor, Ro 12-2272, were compared with two novel inhibitors of lipid metabolism: an inhibitor of human pancreatic lipase (Ro 20-0083) and of hepatic fatty acid synthesis...

A highly divergent route to a variety of quinolizidine alkaloids is described. The enantiomeric precursors and utilized for the synthesis of these alkaloids were constructed stereospecifically from the PET cyclization of the corresponding acetylene tethered alpha-trimethylsilyl amine moieties and , respectively, both of which were synthesised from D-ribose. The polyhydroxy quinolizidine alkaloi...

The mechanism of nutrient-evoked insulin release is clearly complex. One part of that mechanism is postulated to be the activation of the glycogenolytic enzyme acid glucan-1,4-alpha-glucosidase. As nitric oxide (NO) has been found to be a potent inhibitor of glucose-stimulated insulin secretion, we have now investigated a possible influence of exogenous NO and inhibition of endogenous NO produc...

Lymphocytes, monocytes, neutrophilic granulocytes and platelets were each separated to greater than 95% purity from six normal subjects, three patients with Gaucher's disease, two heterozygotes for Gaucher's disease, and one patient with Fabry's disease. Activities of the following acid hydrolases were determined: "acid" (pH 4.0) beta-glucosidase, pH 5.0 beta-glucosidase, alpha-galactosidase, a...

The human adenocarcinoma cell line Caco-2 was used for studies on the biosynthesis and transport of lysosomal acid alpha-glucosidase in polarized epithelial cells. Metabolic labelling revealed that in Caco-2 cells alpha-glucosidase is synthesized as a precursor form of 110 x 10(3) Mr. This form is converted into a precursor of slightly higher Mr (112 x 10(3)) by the addition of complex oligosac...

Membrane associated alpha-glucosidase activity was investigated in a methanogenic bioreactor (MR) and a biosulfidogenic bioreactor (SR). Temperature and pH optima studies showed temperature optima of 50 degrees C and pH optima of 8.0 for the alpha-glucosidases from both the MR and SR. Sulfide (at a concentration of 150 mg l(-1)) resulted in the complete loss of all alpha-glucosidase activity in...

Miglitol is an alpha-glucosidase inhibitor that improves post-prandial hyperglycemia, and it is the only drug in its class that enters the bloodstream. Anecdotally, miglitol lowers patient body weight more effectively than other alpha-glucosidase inhibitors, but the precise mechanism has not been addressed. Therefore, we analyzed the anti-obesity effects of miglitol in mice and in the HB2 brown...

AIM/INTRODUCTION To assess the overall safety and efficacy of lixisenatide in combination with background oral antidiabetic drug treatment in Japanese patients with type 2 diabetes, as required by Japanese guidelines. MATERIALS AND METHODS A phase 3, multicenter, uncontrolled, open-label, four-arm, parallel-group study of Japanese outpatients with type 2 diabetes was carried out; patients rec...

The role of glucose trimming in the endoplasmic reticulum of Saccharomyces cerevisiae was investigated using glucosidase inhibitors and mutant strains devoid of glucosidases I and II. These glucosidases are responsible for removing glucose residues from the N-linked core oligosaccharides attached to newly synthesized polypeptide chains. In mammalian cells they participate together with calnexin...