Drugs online research references
Eur J Pharmacol. 1988 Dec 13;158(3):257-62.
Sulphonamide modulation of sodium content in rat pancreatic islets.
Ali L, Wesslen N, Hellman B.
Department of Medical Cell Biology, Biomedicum, Uppsala, Sweden.
Sodium was measured in rat pancreatic islet exposed to tolbutamide, glipizide, diazoxide or sulfisomidine. When added to a medium with physiologically balanced cations these sulphonamides induced a significant rise of the islet content of sodium. The insulin-releasing compounds, tolbutamide and glipizide, had effects opposite to those of the hyperglycemic diazoxide in counteracting the increase of sodium obtained with removal of K+. The tolbutamide-induced increase in sodium was reversed to a decrease when Ca2+ was omitted from the incubation medium. The increase of sodium, which was also seen with non-hypoglycemic sulphonamides, is itself not sufficient for initiating insulin release. However, it may well represent an important mechanism contributing to the secretory response initiated by Ca2+ entry into the sulfonylurea-depolarized beta-cell.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3075550&dopt=Abstract
Diabetes. 1987 Nov;36(11):1292-6.
Direct effects of sulfonylurea agents on glucose transport in the BC3H-1 myocyte.
Rogers BJ, Standaert ML, Pollet RJ.
Department of Medicine, University of South Florida, Tampa.
The actions of sulfonylurea agents to increase peripheral glucose disposal have been classically ascribed to an ability to potentiate insulin action. However, in the BC3H-1 cultured muscle cell, tolbutamide, glipizide, and glyburide directly provoked more than a twofold increase in 2-deoxyglucose (2-DG) uptake in a dose-dependent manner in the absence of insulin. Tolbutamide (3 mM) enhanced 2-DG uptake by 130% in the presence or absence of insulin and did not significantly change insulin binding or the sensitivity of the insulin response. The onset of tolbutamide-stimulated hexose transport was seen after 30 min and reached a plateau after 12 h. Tolbutamide-stimulated glucose transport was associated with a twofold increase in the Vmax of 2-DG uptake and was completely blocked by 50 microM cytochalasin B, indicating that this action is mediated by increase in cell membrane glucose transporters. We show that sulfonylureas at therapeutic concentrations directly increase glucose transport into muscle cells. Because muscle is the major peripheral target tissue for glucose disposal, these results provide the basis for the therapeutic effect of these agents in improving peripheral glucose disposal in insulin-resistant type II (non-insulin-dependent) diabetes mellitus.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3117607&dopt=Abstract
Diabetes. 1987 Nov;36(11):1320-8.
Different effects of glyburide and glipizide on insulin secretion and hepatic glucose production in normal and NIDDM subjects.
Groop L, Luzi L, Melander A, Groop PH, Ratheiser K, Simonson DC, DeFronzo RA.
Yale University School of Medicine, New Haven, Connecticut.
Glyburide (GB) and glipizide (GZ) differ in their pharmacokinetics, but it is not known whether they also differ in mode of action. To examine this question, 10 young healthy subjects and 6 non-insulin-dependent diabetic (NIDDM) patients participated in each of three studies: 1) infusion of saline for 120 min followed by a 100-min hyperglycemic (125 mg/dl) clamp; 2) 120-min primed continuous infusion of GZ followed by a 100-min hyperglycemic clamp; and 3) 120-min primed continuous infusion of GB followed by a 100-min hyperglycemic clamp. The GB and GZ infusions were continued throughout the hyperglycemic clamp. Similar plasma concentrations of GB and GZ were obtained in both groups. All studies were performed with [3-3H]glucose to allow quantification of hepatic glucose production. When administered under basal conditions of glycemia, the acute phase (0-10 min) of plasma insulin and C-peptide increase in both control and NIDDM subjects was twice as great with GZ compared with GB (P less than .01). During the hyperglycemic-clamp studies performed in normal subjects, both GB and GZ increased the first- (1.6-fold) and second- (2.2-fold) phase plasma insulin responses more than hyperglycemia alone. During the hyperglycemic clamp in NIDDM subjects, the first-phase plasma insulin response was absent, and the second-phase insulin response was markedly impaired. Neither GB nor GZ improved first-phase insulin secretion in the NIDDM patients. In both NIDDM and control subjects, the effects of hyperglycemia and sulfonylurea drugs (both GB and GZ) on the first- and second-phase plasma insulin responses were simply additive.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3117609&dopt=Abstract
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