piperidines and miglitol

Topics: 1-Deoxynojirimycin; Acarbose; Aged; Blood Glucose; Carbamates; Contraindications; Cyclohexanes; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Enzyme Inhibitors; Fasting; Follow-Up Studies; Germany; Glucosamine; Glyburide; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemia; Hypoglycemic Agents; Imino Pyranoses; Insulin; Metformin; Middle Aged; Nateglinide; Obesity; Patient Compliance; Phenylalanine; Pioglitazone; Piperidines; Practice Guidelines as Topic; Risk Factors; Rosiglitazone; Sulfonylurea Compounds; Thiazolidinediones; Time Factors

It is widely accepted that the most challenging goal in the management of patients with diabetes mellitus is to achieve blood glucose levels as close to normal as possible. In general, normalising postprandial blood glucose levels is more difficult than normalising fasting hyperglycaemia. In addition, some epidemiological studies suggest that postprandial hyperglycaemia (PPHG) or hyperinsulinaemia are independent risk factors for the development of macrovascular complications of diabetes mellitus. Recently, several drugs with differing pharmacodynamic profiles have been developed which target PPHG. These include insulin lispro, amylin analogues, alpha-glucosidase inhibitors and meglitinide analogues. Insulin lispro has a more rapid onset of action and shorter duration of efficacy compared with regular human insulin. In clinical trials, the use of insulin lispro was associated with improved control of PPHG and a reduced incidence of hypoglycaemic episodes. Repaglinide, a meglitinide analogue, is a short-acting insulinotropic agent which. when given before meals, stimulates endogenous insulin secretions and lowers postprandial hyperglycaemic excursions. Both insulin lispro and repaglinide are associated with postprandial hyperinsulinaemia. In contrast, amylin analogues reduce PPHG by slowing gastric emptying and delivery of nutrients to the absorbing surface of the gut. Alpha-Glucosidase inhibitors such as acarbose, miglitol and voglibose also reduce PPHG primarily by interfering with the carbohydrate-digesting enzymes and delaying glucose absorption. With the availability of agents which preferentially reduce postprandial blood glucose excursions, it is now possible to achieve glycaemic goals in a larger proportion of individuals with diabetes mellitus.

Topics: 1-Deoxynojirimycin; Acarbose; Amyloid; Carbamates; Diabetes Mellitus; Enzyme Inhibitors; Glucosamine; Glyburide; Humans; Hyperglycemia; Hypoglycemic Agents; Imino Pyranoses; Inositol; Insulin; Insulin Lispro; Islet Amyloid Polypeptide; Piperidines; Postprandial Period; Trisaccharides

In older patients with type 2 diabetes, life expectancy and the presence of microvascular complications determine the appropriate intensity of glucose control. The available antidiabetic agents offer many options for achieving glycemic targets, based on the needs of the individual patient. New stimulators of insulin secretion include glimepiride (a sulfonylurea) and repaglinide (a meglitinide). The biguanide metformin is especially useful in obese, insulin-resistant patients. Alpha-glucosidase inhibitors such as acarbose and miglitol act locally in the GI tract to reduce postprandial excursion in glucose levels. The insulin-sensitizing drug troglitazone enhances insulin-mediated glucose disposal. When troglitazone is used, careful monitoring of patients' liver function is required.

Topics: 1-Deoxynojirimycin; Acarbose; Age Factors; Aged; Blood Glucose; Carbamates; Diabetes Mellitus, Type 2; Glucosamine; Humans; Hypoglycemic Agents; Imino Pyranoses; Metformin; Piperidines; Sulfonylurea Compounds; Trisaccharides

We report the isolation and structural determination of fourteen iminosugars, containing five pyrrolizidines and five indolizidines, from Castanospermum australe. The structure of a new alkaloid was elucidated by spectroscopic methods as 6,8-diepi-castanospermine (13). Our side-by-side comparison between bicyclic and corresponding monocyclic iminosugars revealed that inhibition potency and spectrum against each enzyme are clearly changed by their core structures. Castanospermine (10) and 1-deoxynojirimycin (DNJ) have a common d-gluco configuration, and they showed the expected similar inhibition potency and spectrum. In sharp contrast, 6-epi-castanospermine (12) and 1-deoxymannojirimycin (manno-DNJ) both have the d-manno configuration but the α-mannosidase inhibition of 6-epi-castanospermine (12) was much better than that of manno-DNJ. 6,8-Diepi-castanospermine (13) could be regarded as a bicyclic derivative of talo-DNJ, but it showed a complete loss of α-galactosidase A inhibition. This behavior against α-galactosidase A is similar to that observed for 1-epi-australine (6) and altro-DMDP.

Topics: 1-Deoxynojirimycin; Alkaloids; Castanospermum; Enzyme Inhibitors; Glucosamine; Glycoside Hydrolases; Hypoglycemic Agents; Imino Sugars; Indolizines; Piperidines; Stereoisomerism; Structure-Activity Relationship

Topics: 1-Deoxynojirimycin; Acarbose; Carbamates; Diabetes Mellitus, Type 2; Glucosamine; Humans; Hypoglycemic Agents; Imino Pyranoses; Multicenter Studies as Topic; Pioglitazone; Piperidines; Randomized Controlled Trials as Topic; Thiazoles; Thiazolidinediones