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stolav.no
AIMS: To test whether a bedtime dose of diazoxide can improve daytime beta-cell function without side-effects in Type 2 diabetes. METHODS: A double-blind randomized study was performed in 27 Type 2 diabetic subjects (17 male, 10 female) who were treated with bedtime insulin and metformin. Subjects received either bedtime diazoxide, 100 mg, or placebo for 9 weeks. Duplicate C-peptide glucagon tests were performed before and in the last days of intervention. RESULTS: No side-effects of diazoxide were detected. Treatment with diazoxide did not incur any increase in bedtime insulin. C-peptide responses to glucagon tended to increase: 0.15 +/- 0.06 nmol/l vs. -0.01 +/- 0.04 nmol/l for placebo, P < 0.06 for difference. Corresponding effects on insulin were 66.2 +/- 41.7 pmol/l for diazoxide vs. -84.2 +/- 51.5 for placebo, P < 0.03. Treatment with diazoxide decreased fasting glucagon levels by 41% vs. placebo, P < 0.03. Glycated haemoglobin (HbA1c) levels were not affected, whereas levels of blood glucose post breakfast were higher during diazoxide (1.34 +/- 0.43 mmol/l, P < 0.01 vs. placebo). CONCLUSIONS: Bedtime treatment with diazoxide in Type 2 diabetic subjects on bedtime insulin and metformin has no significant side-effects, does not increase bedtime insulin supplementation, tends to ameliorate beta-cell function but fails to improve metabolic control.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14706058&dopt=Abstract [PubMed - in process]
unimore.it
OBJECTIVE: To evaluate the effects of metformin administration on spontaneous LH episodic release in a group of nonobese polycystic ovary (PCOS) patients. DESIGN: Controlled clinical study. SETTING: PCOS patients in a clinical research environment. PATIENT(S): Twenty nonobese PCOS patients were enrolled after informed consent. INTERVENTION(S): All patients underwent hormonal evaluations and a pulsatility study (sampling every 10 minutes for 4 hours) before and at the sixth month of therapy (metformin, 500 mg, p.o. b.i.d.). Ultrasound examinations and Ferriman-Gallwey scoring were also performed. MAIN OUTCOME MEASURE(S): Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17-hydroxy-progesterone (17-OHP), and testosterone (T), glucose, insulin, and C-peptide concentrations. RESULT(S): After 6 months of metformin administration, the plasma LH, 17-OHP, A, and T levels and LH/FSH ratio were significantly reduced. Insulin sensitivity, expressed as the glucose-to-insulin ratio, was significantly improved under glucose load after 6 months of treatment. Spontaneous LH episodic release showed a significant reduction in pulse amplitude with no changes in pulse frequency. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic women. The ovarian volume and Ferriman-Gallwey scores also were significantly reduced. CONCLUSION(S): Metformin administration improves reproductive axis functioning in hyperandrogenic nonobese PCOS patients. By acting on the ovary and restoring normal ovarian activity, metformin positively modulates the reproductive axis (namely GnRH-LH episodic release).
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14711553&dopt=Abstract [PubMed - in process]
J Hypertens. 1997 Mar;15(3):269-74.
Metformin relaxes rat tail artery by repolarization and resultant decreases in Ca2+ influx and intracellular [Ca2+].
Chen XL, Panek K, Rembold CM.
Cardiovascular Division, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
BACKGROUND: Metformin treatment of type II diabetes is frequently associated with decreases in blood pressure, an effect that could result from a direct action of metformin on arterial smooth muscle. OBJECTIVE: To determine the mechanisms responsible for arterial smooth muscle relaxation induced by acute application of metformin and to evaluate the effect of insulin pretreatment on intracellular [Ca2+] ([Ca2+]i) and contraction in an intact artery. METHODS: We stimulated intact deendothelialized rat tail artery with phenylephrine, relaxed the tissue by adding increasing concentrations of metformin, and measured the membrane potential (Em), Mn2+ influx, Fura 2-estimated [Ca2+]i, and isometric force. We also evaluated the effect of insulin pretreatment on aequorin-estimated [Ca2+]i in deendothelialized swine carotid artery. RESULTS: In rat tail artery we found that a high concentration of metformin-induced repolarization associated with proportional decreases in Mn2+ influx, Fura 2-estimated [Ca2+]i, and isometric force. Incubation of swine carotid artery in 100 mU/ml insulin for 30 min or overnight (16-22 h) did not significantly alter histamine or high-K+-induced increases in [Ca2+]i or contraction. CONCLUSION: These data suggest that acute administration of high concentrations of metformin induces rat tail artery relaxation primarily by repolarization. Additionally, we found that insulin was not vasoactive in the swine carotid artery. It is possible that insulin may alter [Ca2+]i handling in other arteries, in other species, or only in cultured smooth muscle.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9468454&dopt=Abstract
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