Drugs online research references
nwu.edu
The effects of the biguanide anti-hyperglycemic agent, metformin (N,N'-dimethyl-biguanide), on insulin signaling was studied in a human hepatoma cell line (HepG2). Cells were cultured in the absence (control cells) or in the presence of 100 microM of a cholesterol derivative, hemisuccinate of cholesterol. Cholesterol hemisuccinate-treatment alters cholesterol and lipid content of HepG2 and modulates membrane fluidity. Cholesterol hemisuccinate-treatment induces a decrease in insulin responsiveness and creates an 'insulin-resistant' state in these cells. Exposure to 100 microM of metformin resulted in a significant enhancement of insulin-stimulated lipogenesis in control and cholesterol hemisuccinate-treated cells. In control cells, metformin altered glycogenesis in a biphasic manner. In cholesterol hemisuccinate-treated cells, metformin inhibited basal glycogenesis but restored insulin-stimulated glycogenesis. Hence, to understand the mechanism of metformin action, we analyzed early steps in the insulin signaling pathway, including insulin receptor autophosphorylation, mitogen-activated-protein kinase and phosphatidylinositol 3-kinase activities, in both control and cholesterol hemisuccinate-treated cells. Overall, the results suggest that metformin may interact with the insulin receptor and/or a component involved in the early steps of insulin signal transduction.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10456437&dopt=Abstract
Diabetes Res. 1986 Jul;3(6):307-10.
Sulphonylureas and biguanides do not affect insulin binding in H35 hepatoma cells.
De Vries CP, van der Veen EA.
Six sulphonylureas (tolbutamide, tolazamide, chlorpropamide, glibornuride, glipizide and gliquidone) and 2 biguanides (metformin and buformin) were tested for possible effects on insulin binding to H 35 rat hepatoma cells in culture. Insulin binding was measured after 24 and 72 hr of culturing cells in medium containing the drugs. Buformin and gliquidone were tested in concentrations from 10(-8)-5 X 10(-5) M, the other drugs in concentrations from 10(-7)-5 X 10(-4) M. All 24-hr experiments were repeated in cells down-regulated with 10 micrograms/ml insulin. None of the oral hypoglycemic agents tested had any significant influence on insulin binding to H 35 hepatoma cells, either in the presence or absence of insulin. We suggest that the insulin receptor status, at least in this type of liver cell, is not influenced by sulphonylureas or biguanides.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3757414&dopt=Abstract
alpha.lehman.cuny.edu
Metformin, an antihyperglycemic agent used for treatment of type 2 diabetes mellitus, lowers blood pressure in humans and experimental animals. We recently demonstrated that short-term administration of metformin may lower blood pressure by reducing sympathetic neural outflow. The present studies were initiated to determine whether long-term administration of metformin blunts salt-induced hypertension, a condition characterized by elevated sympathetic activity. Male spontaneously hypertensive rats, in which radiotelemeters had been implanted for continuous monitoring of heart rate and blood pressure, were randomly assigned to groups that received vehicle (drinking water) or metformin (500 mg/kg per day) and ate a normal 0.3% NaCl diet and to groups that received vehicle or metformin and ate a high 8.0% NaCl diet for a period of 4 weeks. Although metformin did not affect blood pressure in the animals that ate the normal-salt diet (vehicle, 130+/-3 mm Hg; metformin, 133+/-5 mm Hg; mean+/-SEM), drug treatment blunted the rise in pressure caused by a high-salt diet (vehicle, 153+/-4 mm Hg; metformin, 140+/-5 mm Hg; P<0.001). In agreement, during direct pressure recordings in anesthetized rats, the animals that ate the high-salt diet had higher pressures (136+/-13 mm Hg) than those in the control (98+/-5 mm Hg, P<0.01), metformin (100+/-7 mm Hg, P<0.01), and metformin/high-salt groups (92+/-3 mm Hg, P<0.01). Finally, metformin lowered heart rate in rats that ate the normal- and high-salt diets (310+/-3 and 305+/-4 bpm) compared with rats that ate normal- and high-salt diets given vehicle (332+/-3 and 324+/-2 bpm, P<0.01). These data indicate that the chronic depressor actions of metformin are enhanced in animals with hypertension exacerbated by a high-salt diet.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10334800&dopt=Abstract
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