Drugs online research references
Diabetes Res Clin Pract. 1990 Oct;10(2):167-75.
Insulin release and peripheral sensitivity at the oral glucose tolerance test.
Cederholm J, Wibell L.
Department of Internal Medicine, University Hospital, Uppsala, Sweden.
With the use of a 75 g oral glucose tolerance test, both insulin release (IRG) and the degree of peripheral sensitivity (SI) were evaluated simultaneously in groups with normal (NGT) and impaired (IGT) glucose tolerance as well as NIDDM. IRG was expressed as the ratio of the area under the insulin curve to that of the glucose curve above fasting levels. The peripheral glucose uptake rate (M) during the OGTT was measured as the difference between the glucose load and the increase in the amount of glucose in the glucose space during the oral glucose tolerance test (OGTT). SI was expressed as the ratio of the metabolic clearance rate (M/mean blood glucose) to log mean serum insulin. In the non-obese groups, both mean IRG and mean SI values were decreased with an increasing degree of hyperglycemia from NGT to NIDDM. Decreased mean SI values were also found in obese subjects. IGT-subjects given 3 months of diet and exercise achieved improved SI values. A non-obese NIDDM-group had higher mean IRG and mean SI values after 6 months of treatment with glipizide. The results were comparable to data obtained with more complicated techniques, such as the insulin clamp and suppression tests, and should be easy to apply on a large scale in epidemiological studies.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2261853&dopt=Abstract
J Biol Chem. 1987 Nov 25;262(33):15840-4.
The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K+ channel in insulin-secreting cells.
Schmid-Antomarchi H, De Weille J, Fosset M, Lazdunski M.
Centre de Biochimie du Centre National de la Recherche Scientifique, Nice, France.
Sulfonylureas are powerful hypoglycemic drugs that have been used for decades to treat diabetic patients. This paper describes a 86Rb+ flux technique that permits one to study easily the properties of ATP-modulated K+ channels in RINm5F insulinoma cells. Sulfonylureas inhibit this type of K+ channel under conditions of intracellular ATP depletion. The most potent sulfonylureas (glibenclamide, glipizide, and gliquidone) are acting in the nanomolar range of concentration. Inhibition of the single ATP-modulated K+ channels by low concentrations of sulfonylureas was also observed using the patch-clamp technique. The sulfonylurea receptor has been biochemically identified with [3H]glibenclamide. For 10 different sulfonylureas (or sulfonylurea analogs) there was an excellent correlation between efficacy of blockade of ATP-modulated K+ channels and efficacy of binding to the sulfonylurea receptors using the 3H-ligand.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2445740&dopt=Abstract
Naunyn Schmiedebergs Arch Pharmacol. 1988 Feb;337(2):225-30.
Concentration-dependent effects of tolbutamide, meglitinide, glipizide, glibenclamide and diazoxide on ATP-regulated K+ currents in pancreatic B-cells.
Zunkler BJ, Lenzen S, Manner K, Panten U, Trube G.
Institut fur Pharmakologie und Toxikologie, Universitat Gottingen, Federal Republic of Germany.
The influence of the hypoglycemic drugs tolbutamide, meglitinide, glipizide and glibenclamide on ATP-dependent K+ currents of mouse pancreatic B-cells was studied using the whole-cell configuration of the patch-clamp technique. In the absence of albumin, tolbutamide blocked the currents half maximally at 4.1 mumol/l. In the presence of 2 mg/ml albumin half maximal inhibition of the currents was observed at 2.1 mumol/l meglitinide, 6.4 nmol/l glipizide and 4.0 nmol/l glibenclamide. The hyperglycemic sulfonamide diazoxide opened ATP-dependent K+ channels. Half maximally effective concentrations of diazoxide were 20 mumol/l with 0.3 mmol/l ATP and 102 mumol/l with 1 mmol/l ATP in the recording pipette. Thus, the action of diazoxide was dependent on the presence of ATP in the recording pipette. The free concentrations of the drugs which influenced ATP-dependent K+ currents were comparable with the free plasma concentrations in humans and the free concentrations which affected insulin secretion in vitro. The results support the view that the target for the actions of sulfonylureas and of diazoxide is the ATP-dependent K+ channel of the pancreatic B-cell or a structure closely related to this channel.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2452991&dopt=Abstract
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