Drugs online research references
J Pharmacol Exp Ther. 1993 Mar;264(3):1293-8.
Alteration of rat hepatic insulin metabolism by glyburide and glipizide.
Chen H, Hamel FG, Siford G, Duckworth WC.
Department of Veterans Affairs Medical Center, Department of Research, Omaha, Nebraska.
The sulfonylurea class of compounds has demonstrated its effectiveness in treating non-insulin-dependent diabetes mellitus, although the exact mechanisms of action are still not fully defined. Clinical studies have suggested the action may be at least in part due to alterations of insulin's effect on liver. We have examined the effects of glyburide and glipizide on insulin metabolism in isolated hepatocytes and perfused livers. Our studies show that both drugs increase insulin binding to hepatocyte, but only glyburide-treated animals exhibit a concomitant increase in degradation. Studies with recycling perfused liver agreed with these results, with glyburide treatment causing a significantly more rapid clearance than control or glipizide treatment. Single-pass perfusion studies showed significantly less insulin retained by glipizide-treated animals as compared to control- and glyburide-treated animals. Further, hepatocytes from glipizide-treated animals required higher concentrations of insulin to achieve the same stimulation of amino acid transport (as measured by aminoisobutyric acid uptake) as in control- and glyburide-treated animals, suggesting that the altered processing affects insulin's action. Taken together, these studies demonstrate alterations in liver insulin metabolism that may explain clinical differences identified in these two drugs.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8450464&dopt=Abstract
Clin Pharmacol Ther. 1993 Mar;53(3):380-4.
Bedtime insulin added to daytime sulfonylureas improves glycemic control in uncontrolled type II diabetes.
Miller JL, Salman K, Shulman LH, Rose LI.
Department of Medicine, Hahnemann University School of Medicine, Philadelphia, PA.
BACKGROUND: To evaluate the possible benefits of the addition of intermediate-acting insulin administered at bedtime to therapy with daytime sulfonylureas in patients with non-insulin-dependent diabetes mellitus for whom maximal doses of oral hypoglycemic agents have not been successful. METHODS: Study subjects were 16 consecutive obese patients aged from 44 to 78 years (mean age, 62 years) with histories of non-insulin-dependent diabetes mellitus for a mean of 9 years. None of the subjects had been able to control their diabetes with maximal doses of oral hypoglycemic agents. All patients received 20 mg glipizide or 10 mg glyburide twice a day, as well as education about the American Diabetes Association diet. Neutral protamine Hagedorn (NPH) insulin was empirically added in doses from 0.1 to 0.2 units/kg given at bedtime. The dose was adjusted on the basis of fasting blood glucose levels. RESULTS: Mean fasting blood glucose decreased from 13.7 +/- 3.4 to 8.3 +/- 2.7 mmol/L at 3 months and 7.3 + 2.0 mmol/L at 1 year. Glycosylated hemoglobin decreased from 9.0% +/- 1.9% to 6.2% +2- 1.16% at 3 months and 6.3% +/- 1.22% at 1 year. CONCLUSION: A late-night dose of NPH insulin was added to a regimen of daytime sulfonylureas in a group of obese patients with type II diabetes whose hyperglycemia was not controlled with maximal doses of oral hypoglycemic agents. This treatment proved to be beneficial and is a useful alternative to conventional insulin therapy in this group of patients.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8453858&dopt=Abstract
Life Sci. 1993;52(19):1527-34.
Disturbances in autoregulatory responses of rat pial arteries by sulfonylureas.
Lee WS, Kwon YJ, Yu SS, Rhim BY, Hong KW.
Department of Pharmacology, College of Medicine, Pusan National University, Korea.
It was aimed to test the role of ATP-sensitive K+ channels in the autoregulatory response of cerebral arterioles in vivo. Changes in pial arterial caliber (mean, 43.2 +/- 2.3 microns in diameter) in response to changes in systemic arterial blood pressure (mean, 104.3 +/- 1.4 mmHg) were observed directly through closed cranial windows in anesthetized normotensive rats. During superfusion with vehicle, pial arterial caliber automatically increased in response to hypotension induced by arterial bleeding into a reservoir and decreased on reverse of arterial blood pressure by infusion of blood. After pretreatment with sulfonylureas, glibenclamide (1 and 3 microM) and glipizide (30 and 100 microM), arteriolar dilatation and constriction observed during hypotension and its reverse were disturbed. A similarity was evidenced when hypotension was induced by sodium nitroprusside (750 nmol kg-1min-1, i.v.). Cromakalim, a K+ channel opener, exerted a concentration-dependent vasodilatation of the pial artery and its effect was antagonized by glibenclamide. These data suggest that the endogenous glibenclamide-sensitive K+ channel opener is involved in the modulation of cerebral microvascular autoregulation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8483381&dopt=Abstract
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