Drugs online research references
Am J Physiol Endocrinol Metab. 2004 Feb 10 [Epub ahead of print]
Metformin, but not leptin, regulates AMP-activated protein kinase in pancreatic islets: impact on glucose-stimulated insulin secretion.
Leclerc I, Woltersdorf WW, Da Silva Xavier G, Rowe RL, Cross SE, Korbutt GS, Rajotte RV, Smith R, Rutter GA.
Henry Wellcome Laboratories for Integrated Cell Signalling and Department of Biochemistry, University of Bristol, Bristol, United Kingdom.
Metformin, a drug widely used in the treatment of Type 2 diabetes, has recently been shown to act on skeletal muscle and liver in part through the activation of AMP-activated protein kinase (AMPK). Whether metformin or the satiety factor leptin, which also stimulates AMPK in muscle, regulate this enzyme in pancreatic islets, is unknown. We have recently shown that forced increases in AMPK activity inhibit insulin secretion from MIN6 cells (da Silva Xavier et al, Biochem. J 371:761-774, 2003). Here, we explore whether (a) glucose, metformin or leptin regulate AMPK activity in isolated islets from rodent and human, and (b) whether changes in AMPK activity modulate insulin secretion from human islets. Increases in glucose concentration from 0 to 3 and 3 to 17 mM inhibited AMPK activity in primary islets from mouse, rat and human, confirming previous findings in insulinoma cells. Incubation with metformin (0.2 - 1 mM) activated AMPK in both human islets and MIN6 beta-cells in parallel with an inhibition of insulin secretion, whereas leptin (10 - 100 nM) was without effect in MIN6 cells. These studies demonstrate that AMPK activity is subject to regulation by both glucose and metformin in pancreatic islets and clonal beta- cells. The inhibitory effects of metformin on insulin secretion may therefore need to be considered in respect to the use of this drug for the treatment of Type 2 diabetes.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14871885&dopt=Abstract [PubMed - as supplied by publisher]
J Chromatogr Sci. 2004 Jan;42(1):27-31.
Simultaneous high-performance liquid chromatographic determination of pioglitazone and metformin in pharmaceutical-dosage form.
Kolte BL, Raut BB, Deo AA, Bagool MA, Shinde DB.
Department of Chemical Technology, Dr Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra State, India.
A simple, rapid, and precise method is developed for the quantitative simultaneous determination of metformin and pioglitazone in a combined pharmaceutical-dosage form. Separation is achieved with a Zorbax XDB C(18), 15-cm analytical column using buffer-acetonitrile (66:34, v/v) of pH 7.1, adjusted with orthophosphoric acid as the mobile phase. The buffer used in the mobile phase contains 10mM disodium hydrogen phosphate and 5mM sodium dodecyl sulphate in double-distilled water. The instrumental settings are flow rate of 1 mL/min, column temperature at 40 degrees C, and detector wavelength of 226 nm. The internal standard method is used for the quantitation of the ingredients of this combination. Methylparaben is used as an internal standard. The method is validated and shown to be linear for metformin and pioglitazone. The correlation coefficients for metformin and pioglitazone are 0.9991 and 0.9999, respectively. The relative standard deviations for six replicate measurements in two sets of each drug in the tablets are always less than 2%.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14965412&dopt=Abstract [PubMed - in process]
Fertil Steril. 2004 Feb;81(2):355-60.
Nonobese women with polycystic ovary syndrome respond better than obese women to treatment with metformin.
Maciel GA, Soares Junior JM, Alves Da Motta EL, Abi Haidar M, De Lima GR, Baracat EC.
Department of Gynecology, Division of Gynecological Endocrinology, Federal University of Sao Paulo, Escola Paulista de Medicina, Sao Paulo, Brazil.
OBJECTIVE: To determine the clinical, hormonal, and biochemical effects of metformin therapy in obese and nonobese patients with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Department of Gynecology of Federal University of Sao Paulo, Sao Paulo, Brazil. PATIENT(S): Twenty-nine patients with PCOS. INTERVENTION(S): Patients were treated with 500 mg of p.o. metformin t.i.d. for 6 months. MAIN OUTCOME MEASURE(S): Clinical data as well as serum concentrations of sex steroids, sex hormone-binding globulin (SHBG), gonadotropins, leptin, GH, lipids, insulin, and glucose levels were assessed before and after treatment. RESULT(S): In the metformin group of nonobese patients, the mean fasting serum insulin concentration decreased from a pretreatment value of 12.1 +/- 2.4 to 6.3 +/- 0.6 microU/mL after treatment, and the area under the curve of insulin decreased from 5,189.1 +/- 517.4 to 3,035.6 +/- 208.9 microU/mL per minute. Also in the metformin group of nonobese patients, the mean basal serum total testosterone, free testosterone, and androstenedione concentrations decreased by 38%, 58%, and 30%, respectively. In the obese patients treated with metformin, only free testosterone showed a statistically significant decrease (1.7 +/- 0.2). CONCLUSION(S): Our data suggest that nonobese patients respond better than obese patients to a 1.5 g/day metformin regimen.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14967373&dopt=Abstract [PubMed - in process]
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