Drugs online research references
Diabete Metab. 1990 Dec;16(6):473-8.
Diurnal pattern of plasma metformin concentrations and its relation to metabolic effects in type 2 (non-insulin-dependent) diabetic patients.
Marchetti P, Gregorio F, Benzi L, Giannarelli R, Cecchetti P, Villani G, Di Cianni G, Di Carlo A, Brunetti P, Navalesi R.
Istituto di Clinica Medica Generale e Terapia Medica II, University of Pisa, Italy.
The authors describe the diurnal profile of plasma metformin concentrations in a group of 6 Type 2 (noninsulin-dependent) diabetic patients studied at two different daily metformin doses (500 mg and 850 mg b.d.) and report data on the relationships between plasma metformin and metabolic effects over a 14 h period. In addition, the effect of circulating metformin on insulin binding to isolated monocytes has been evaluated. At the two different daily doses fasting plasma metformin concentrations were similar (3.23 +/- 0.35 mumol/l and 3.86 +/- 0.72 mumol/l, mean values +/- SEM, at low and high dose respectively). Drug peak values and averaged concentrations (4.66 +/- 0.39 mumol/l vs 6.35 +/- 0.69 mumol/l) were significantly higher when more drug was administered. Mean plasma glucose was lower when 1,700 mg/day instead of 1,000 mg/day of metformin was given (7.3 +/- 0.4 mmol/l vs 9.1 +/- 0.9 mmol/l, p less than 0.05). After dosing, at higher plasma metformin concentrations corresponded lower plasma glucose values. The averaged blood lactate levels resulted 1.46 +/- 0.4 mmol/l (p less than 0.05 vs matched diet treated diabetic patients) at the higher drug dose. A significant positive correlation emerged between mean plasma metformin concentrations and mean blood lactate levels (r: 0.76, p less than 0.02). Alanine, glycerol and B-OH-butyrate levels were similar at the two metformin daily doses, and were not correlated to plasma metformin. The binding of insulin to isolated human monocytes was similar in metformin-treated diabetic patients (4.48 +/- 0.45) as in healthy volunteers (4.62 +/- 0.34); insulin binding was correlated (p less than 0.05) with plasma metformin levels.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2086278&dopt=Abstract
Diabete Metab. 1984 Dec;10(5):311-5.
Influence of metformin on metabolic effect of insulin in human adipose tissue in vitro.
Cigolini M, Bosello O, Zancanaro C, Orlandi PG, Fezzi O, Smith U.
To study the mechanism(s) of action of metformin, fragments of human subcutaneous adipose tissue were incubated with therapeutic blood concentrations of metformin. In the absence of insulin no effect of metformin was seen on either lipolysis or glucose metabolism. When insulin was present, however, metformin stimulated glucose conversion into both triglycerides and CO2. In marked contrast, no effect of metformin was observed on the antilipolytic effect of insulin. In agreement with this selective effect no change in insulin binding was found. In conclusion, metformin seems to exert its effect on glucose metabolism by potentiating the action of insulin at a post-receptor level, possibly on the rate of glucose transport.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6397366&dopt=Abstract
Atherosclerosis. 1983 Apr;47(1):7-17.
Metformin action on lipid metabolism in lesions of experimental aortic atherosclerosis of rabbits.
Marquie G.
The aim of the present study was to investigate whether metformin was capable of altering aortic lipid metabolism during the progression and regression of cholesterol-induced atherosclerosis in rabbits. Three hours after intravenous injection of a 200-microCi tracer dose of [2-14C]acetate, metformin (120 mg/kg per os) strongly diminished the radioactivity in all lipid fractions of the aorta of the normal rabbit. The incorporation of acetate into lipids was greater in the fatty streaks of rabbits fed cholesterol for 2 months than in normal aorta, independent of the plasma radioactivity level. There was increased acetate incorporation into all major lipid groups in the fatty streak, with the greatest relative increase in the cholesteryl ester fraction. No change was observed in the acetate incorporation into lipids in atheromatous deposits after pretreatment of cholesterol-fed rabbits for 8 days with metformin. Concomitant treatment for 2 months with metformin in rabbits fed a cholesterol-enriched diet strongly reduced the radioactivity of total aortic lipids 3 h after intravenous injection of labelled acetate. The inhibition of acetate incorporation into arterial lipids was observed in all lipid fractions (i.e. free cholesterol, free fatty acids, triglycerides and especially esterified cholesterol and phospholipids). In rabbits fed a cholesterol-enriched diet for a period of two months, followed by a normal diet during 12 months, long-term treatment with metformin significantly reduced total lipid radioactivity in the aorta, 3 h after intravenous injection of the 200-microCi tracer dose of [2-14C]acetate. The incorporation of labelled precursor was markedly reduced in the various lipid fractions. These properties, added to others previously described, can to a large extent explain the protective effect of metformin on experimental atherosclerosis.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6870991&dopt=Abstract
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