Drugs online research references
Probl Endokrinol (Mosk). 1994 Nov-Dec;40(6):47-50.
[Characterization of pancreatic beta cell receptors binding sulfanilamide drugs]
[Article in Russian]
Babichev VN, Savel'eva MP, Balabolkin MI.
Analysis of pancreatic beta-cell receptors binding the sulfanilamide drugs widely used in therapy of type II diabetes, such as glibenclamide, glipizide, and gliclazide, showed that these drugs are characterized by excellent parameters of specific binding to these receptors. The receptors were tested for two parameters: number of binding sites and dissociation constant. Glibenclamide was the most active of the drugs we tested, the other two agents being less active. Binding of these agents was reversible. The problem of identification of the examined receptors of sulfanilamides with K(+)-ATP-sensitive channels, similarly active conductors of the information transported by the sulfanilamide drugs in the mechanism of insulin secretion, is discussed.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7740038&dopt=Abstract
Diabetes Care. 1994 Oct;17(10):1093-9.
Effect of metformin on postprandial lipemia in patients with fairly to poorly controlled NIDDM.
Jeppesen J, Zhou MY, Chen YD, Reaven GM.
Department of Medicine, Stanford University School of Medicine, California.
OBJECTIVE--To quantify the effect of metformin on the metabolism of triglyceride (TG)-rich lipoprotein of intestinal origin in patients with non-insulin-dependent diabetes mellitus (NIDDM) who had responded to sulfonylurea but still had fasting hyperglycemia. RESEARCH DESIGN AND METHODS--Sixteen patients with NIDDM who had demonstrated a fall in fasting plasma glucose concentration > 2.2 mmol/l in response to glipizide treatment but continued to have fasting plasma glucose concentrations > 8.3 mmol/l were studied. Fasting glucose, GHb, lipid and lipoprotein concentrations were determined, and resistance to insulin-mediated glucose disposal was estimated by measuring the steady-state plasma glucose (SSPG) concentration at the end of a 180-min infusion of somatostatin, glucose, and insulin. In addition, plasma glucose, insulin, and TG concentrations were measured at frequent intervals from 0800 to 2400, with patients eating breakfast at 0800 and lunch at 1200. Vitamin A was also given at lunch, and the retinyl ester content in plasma and in chylomicron (Svedberg flotation constant [Sf] > 400) and the chylomicron remnant (Sf 20-400) fractions were used to quantify the concentration of postprandial intestinal TG-rich lipoprotein from 1200 to 2400. RESULTS--Fasting plasma glucose concentrations (6.8 +/- 0.4 vs. 10.5 +/- 0.4 mmol/l), GHb levels (7.9 +/- 0.3 vs. 10.8 +/- 0.5%), and day-long plasma glucose concentrations were all significantly lower after metformin treatment (P < 0.001), which was associated with a significant (P < 0.001) fall in SSPG concentration (11.0 +/- 0.9 to 9.6 +/- 0.6 mmol/l). In addition, postprandial concentrations of glucose, insulin, free fatty acids, and TG were lower (P < 0.001) following metformin treatment. Postprandial retinyl ester concentrations were also lower in plasma by 33 +/- 5.7% (P < 0.001) and in both the chylomicron (32 +/- 7.2%, P < 0.001) and chylomicron remnant (26 +/- 7.0%, P < 0.005) fractions. CONCLUSIONS--Addition of metformin to sulfonylurea-treated patients with NIDDM with less than optimal glycemic control was associated with improved glycemic control, lower postprandial insulin and TG concentrations, and a decrease in postprandial concentration of TG-rich lipoproteins of intestinal origin. All of these changes might be expected to decrease risk of coronary heart disease.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7821127&dopt=Abstract
Biochem Med Metab Biol. 1994 Oct;53(1):22-7.
Insulinotropic action of formycin A.
Malaisse WJ, Sener A, Gruber HE, Erion MD.
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
The adenosine analogue formycin A is phosphorylated to its triphosphate ester in a sequence of reactions catalyzed by adenosine kinase and adenylate kinase. Formycin A triphosphate is an ATP analogue that is currently used to probe for ATP binding sites. Considering the key role ascribed to ATP in the coupling of metabolic to cationic events in the process of glucose-stimulated insulin release, we investigated whether formycin A displays insulinotropic action in rat pancreatic islets. Formycin A (10 microM to 1.0 mM) caused a concentration-related increase of insulin release evoked by 8.3 mM D-glucose and prevented the fall in insulin output otherwise observed over two successive incubations of 90 min each. Formycin A (1.0 mM) also augmented insulin secretion at low (5.6 mM) and high (16.7 mM) concentrations of D-glucose. At the low hexose concentration, the secretory response to formycin A was comparable to that evoked by either glibenclamide or glipizide. At higher concentrations of D-glucose, however, formycin A was more potent than the hypoglycemic sulfonylureas in enhancing insulin output. These findings support the role of ATP in glucose-stimulated insulin release and, therefore, suggest that ATP mimetics represent a new class of insulinotropic agents that have potential utility in the treatment of non-insulin-dependent diabetes mellitus.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7857678&dopt=Abstract
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