Drugs online research references
Diabetes. 1993 Aug;42(8):1159-65.
Metformin blocks downregulation of cell surface GLUT4 caused by chronic insulin treatment of rat adipocytes.
Kozka IJ, Holman GD.
Department of Biochemistry, University of Bath, Claverton Down, United Kingdom.
Large decreases in insulin-responsive glucose transport occur in rat adipocytes maintained in culture for 24 h in the continuous presence of insulin. After 24 h in culture, an acute treatment with insulin increased 3-O-methyl-D-glucose transport by only approximately fivefold. In chronically insulin-treated cells, the transport activity was more severely reduced. The transport activity was only approximately twofold higher than in basal cells. To attribute changes in transport to alterations in cell surface transporters, we labeled the cell surface GLUT4 and GLUT1 transporters with the impermeant photoaffinity label 2-N-[4-(1-azi-2,2,2-trifluoroethyl)benzoyl]-1,3-bis(D-mannos -4-yloxy)-2- propylamine. Cell surface labeling was compared with the labeling obtained in digitonin-permeabilized cells where the normally impermeant reagent had access to the total cellular pool of transporters. Labeling showed that in basal cells the proportions of GLUT4 and GLUT1 at the cell surface were 20 and 22% of the total. After an acute treatment with insulin, the proportions of GLUT4 and GLUT1 at the cell surface were increased to 49 and 37% of the total, respectively. The chronic insulin treatment was associated with a very low proportion of GLUT4 (25% of the total) at the cell surface. The downregulation of GLUT4 observed after chronic insulin treatment was alleviated by metformin, and the proportion of GLUT4 at the cell surface was maintained at 60% of the total.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8325447&dopt=Abstract
pol.net
Recently, the number of agents to treat type 2 diabetes has increased markedly. In the past, the only agents practitioners had available to treat patients with type 2 diabetes mellitus were insulin and sulfonylureas. Today, three additional classes of agents with a total of six new drugs are available: acarbose, migital, repaglinide, metformin hydrochloride, troglitazone, and rosiglitazone. In the not-too-distant future, several other agents will be available for treating patients with diabetes. These new agents will allow physicians to control their diabetic patients' blood sugar levels without the need for insulin injections. This article reviews the new agents and provides practical suggestions regarding their use as monotherapy or in combination therapy.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10659525&dopt=Abstract
alpha.lehman.cuny.edu
The antidiabetic drug metformin lowers blood pressure (BP) more in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY), and the hypotensive effect is enhanced by high dietary salt. To determine whether enhanced hypotension is secondary to greater decreases in sympathetic nerve activity (SNA), we placed WKY and SHR on normal salt (0.3%), and SHR on high salt (8.0%) for 2 weeks and then measured anesthetized BP and lumbar SNA to metformin (0, 10, 50, and 100 mg/kg, given intravenously). Baseline BP were similar in SHR groups but lower in WKY. Although metformin decreased BP more in high salt SHR (50 mg/kg: deltaBP: -23+/-1 mm Hg) than in normal salt SHR (-14+/-1 mm Hg, P< .01) and less in WKY (-10+/-1 mm Hg, P<.05), equivalent decreases in SNA were observed. We conclude that both strain and high salt potentiate acute depressor responses to metformin through mechanisms that are independent of SNA.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10619590&dopt=Abstract
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