Drugs online research references
J Natl Med Assoc. 1997 Nov;89(11):728-30.
A retrospective analysis of the efficacy and safety of metformin in the African-American patient.
Briscoe TA, Anderson D, Usifo OS, Cooper GS.
Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia 30310, USA.
A retrospective analysis was conducted to determine the effects of metformin on glycosylated hemoglobin (HbA1c), body weight, and adverse events in an African-American population. Thirty-six patients who were receiving combination therapy with metformin and either a sulfonylurea or insulin were identified from a hospital pharmacy database. Nineteen patients met the criteria for efficacy analysis. The combination of metformin with either a sulfonylurea or insulin resulted in a decrease of the average HbA1c from a baseline of 10.07% to 7.92% (delta = 2.15%). The effect of combination therapy on weight was variable; however, twice as many patients lost weight compared with those who gained weight. Metformin appeared to be well-tolerated, with gastrointestinal symptoms being the most commonly reported adverse events.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9375476&dopt=Abstract
Endocrinology. 1992 May;130(5):2535-44.
Stimulation of hexose transport by metformin in L6 muscle cells in culture.
Klip A, Guma A, Ramlal T, Bilan PJ, Lam L, Leiter LA.
Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
L6 muscle cells grown in culture to the stage of fused myotubes were incubated with the oral hypoglycemic drug metformin to test the effects of this drug on glucose transport. Metformin increased the initial rate of uptake of 2-deoxyglucose and 3-O-methylglucose. The effect was time dependent, with half-maximal stimulation at 5-6 h and maximal stimulation by about 16 h. The stimulation of hexose uptake was not prevented by cycloheximide. In 15 mM glucose medium, the basal rate of transport was lower than in 5 mM glucose medium. The stimulation of hexose uptake by metformin was comparable in absolute units in both media; hence, relative to basal uptake, stimulation was greater in the high glucose medium than in the low glucose medium. In 5 mM glucose medium, half-maximal stimulation was obtained with 800 microM metformin when tested for 24 h. The stimulation of hexose transport by metformin was only detectable in fused myotubes and not in perfusion myoblasts. No significant changes were observed in glucose transporter levels in total cell membranes from L6 myotubes (measured as D-glucose-protectable binding sites for cytochalasin-B) or in the total levels of the immunoreactive glucose transporter isoforms GLUT4 or GLUT1. It is concluded that metformin stimulates hexose transport into differentiated muscle cells by acting at a posttranslational level. We speculate that this might also constitute the basis for the ability of the drug to lower glycemia in diabetic individuals.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1572281&dopt=Abstract
Metabolism. 1994 May;43(5):591-8.
Regulation of glucose transport and expression of GLUT3 transporters in human circulating mononuclear cells: studies in cells from insulin-dependent diabetic and nondiabetic individuals.
Estrada DE, Elliott E, Zinman B, Poon I, Liu Z, Klip A, Daneman D.
Department of Pediatrics (Endocrine Division), Hospital for Sick Children, Toronto, Ontario, Canada.
We have previously shown that human circulating mononuclear cells (CMCs) respond to physiological concentrations of insulin with a rapid increase in glucose transport rate. The responding cells were found to be the monocytes, and cells derived from individuals with insulin-dependent diabetes mellitus (IDDM) had lower basal and insulin-stimulated glucose transport rates. Of interest, both cell types were found to express the GLUT1 but not the typical insulin-responsive GLUT4 transporter isoform. To further study the mechanisms responsible for stimulation of transport in these cells, we investigated (1) the response to insulin-like growth factor-I (IGF-I) and insulin-mimetic agents, and (2) the expression of other glucose transporter isoforms in CMCs of nondiabetic and IDDM individuals. The time course of insulin-stimulated glucose uptake in CMCs was rapid, reaching a plateau within 30 minutes. CMCs showed a dose-dependent and highly sensitive increase in glucose uptake to IGF-I (maximal response reached at 0.1 to 0.5 nmol/L IGF-I). The IGF-I dose-response curve was similar for CMCs of control and IDDM individuals, but both the basal and maximal response to IGF-I were lower in the diabetic group (P < .01). CMCs did not respond to vanadate, lithium, hydrogen peroxide, or short incubation (1 hour) with metformin, but glucose uptake increased in response to peroxides of vanadate and longer-duration (14 hours) metformin incubations. The glucose transporter isoforms of separated monocytes and lymphocytes were further investigated by Northern blotting of total RNA with a GLUT3-specific cDNA probe and by Western blotting of total membranes using GLUT3-specific antiserum.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8177047&dopt=Abstract
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