Drugs online research references
Diabetes. 2000 May;49(5):735-40.
Metformin restores insulin secretion altered by chronic exposure to free fatty acids or high glucose: a direct metformin effect on pancreatic beta-cells.
Patane G, Piro S, Rabuazzo AM, Anello M, Vigneri R, Purrello F.
Department of Internal Medicine, Signorelli Diabetes Center, University of Catania, Ospedale Garibaldi, Italy.
Because metformin affects glucose and free fatty acid (FFA) metabolism in peripheral insulin target tissues, we investigated the effect of this drug in restoring a normal secretory pattern in rat pancreatic islets whose function has been impaired by chronic exposure to elevated FFA or glucose concentrations. We cultured rat pancreatic islets with or without FFA (2 mmol/l oleate/palmitate 2:1) or high glucose (16.7 mmol/l) concentrations in the presence or absence of metformin (0.25-12.5 microg/ml) and then measured insulin release, glucose utilization, glucose, and FFA oxidation. When compared with control islets, islets exposed to high FFA or glucose concentrations showed an increased basal and a decreased glucose-induced insulin release. In islets cultured for an additional 24 h with FFA or glucose in the presence of metformin (2.5 microg/ml), both basal and glucose-induced insulin secretions were restored. Both glucose utilization and glucose oxidation were altered in islets pre-exposed to high FFA or glucose concentrations. In particular, regarding control islets, glucose utilization was increased at 2.8 mmol/l glucose and decreased at 16.7 mmol/l glucose; glucose oxidation was similar to control islets at 2.8 mmol/l glucose but decreased at 16.7 mmol/l glucose. In contrast, oleate oxidation was increased in islets pre-exposed to FFA. All of these abnormalities were reversed in islets cultured for an additional 24 h with high FFA or glucose concentrations in the presence of metformin (2.5 microg/ml). In conclusion, our data show that metformin is able to restore the intracellular abnormalities of glucose and FFA metabolism and to restore a normal secretory pattern in rat pancreatic islets whose secretory function has been impaired by chronic exposure to elevated FFA or glucose levels. These data raise the possibility that, in diabetic patients, metformin (in addition to its peripheral effects) may have a direct beneficial effect on the beta-cell secretory function.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10905481&dopt=Abstract
Biochem Pharmacol. 1996 Apr 12;51(7):893-6.
Effect of metformin on SGLT1, GLUT2, and GLUT5 hexose transporter gene expression in small intestine from rats.
Lenzen S, Lortz S, Tiedge M.
nstitute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
The effect of the antihyperglycaemic agent metformin was studied on gene expression of the energy-dependent sodium-hexose cotransporter (SGLT1) and the facilitative hexose transporters GLUT2 and GLUT5 in rat intestine. Metformin treatment (125 mg/kg body wt. twice daily for a period of 3 days) significantly increased SGLT1 gene expression in duodenum and jejunum. GLUT5 gene expression was increased by metformin treatment only in the jejunum. Gene expression of GLUT2 in the intestine was not significantly affected by metformin treatment. This increase in transporter gene expression offers the potential for increases in hexose uptake at the brush border membrane, and may compensate for other effects of the drug that have been suggested to decrease glucose uptake by SGLT1, as well as for metformin stimulation of glucose utilization by the intestinal mucosa.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8651938&dopt=Abstract
Horm Metab Res Suppl. 1985;15:111-5.
Incidence of severe sideeffects during therapy with sulfonylureas and biguanides.
Berger W.
The most important side-effect of sulfonylureas is hypoglycaemia. According to surveys in Switzerland and in Sweden it occurs at a frequency of about 2 cases per 10,000 treatment years. Mortality is high, about 10%. The syndrome of inappropriate ADH-secretion has been observed almost exclusively during treatment with chlorpropamide. Asymptomatic cases of SIADH-syndrome are quite frequent, hyponatraemia has been observed in 6-10% of diabetics treated with chlorpropamide. The most dangerous side-effect of biguanides is lactic acidosis. It occurs significantly more frequent during treatment with phenformin compared to metformin. Metformin has been reported to lead to lactic acidosis in 0.4 cases per 10,000 treatment years; mortality is about 30%. Mortality of phenformin-associated lactic acidosis is even higher, 70%. Both biguanides, phenformin and metformin, cause relatively frequently vitamin B12-malabsorption (in about 1/3 of the cases). However, symptomatic vitamin B12-deficiency is extremely rare.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3865878&dopt=Abstract
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