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Chemical Compound Review

AC1L1RMF     N-[2-[4- (cyclohexylcarbamoylsulfamoyl) phen...

Synonyms: A819761
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Disease relevance of glipizide

  • Diazoxide, glipizide, hypertension and hypoglycaemia [1].
  • The effect of glipizide treatment on diabetic control and on in vivo insulin secretion and action was studied in 20 patients with non-insulin-dependent diabetes mellitus (NIDDM) [2].
  • Once a stable diabetic state was established, cats were randomly assigned to groups treated with either glipizide or insulin at doses appropriate to control hyperglycemia [3].
  • Glipizide did not affect total pancreatic blood flow, but decreased islet blood flow by 50% in the presence of hypoglycemia [4].
  • We also observed that the inhibitory effects of SRIF and EPI on insulin were nonadditive, that both hormones were additive to nickel chloride during inhibition of insulin release, and that they noncompetitively inhibited glipizide-induced insulin secretion through pertussis toxin-sensitive mechanisms [5].

Psychiatry related information on glipizide


High impact information on glipizide

  • In the patients receiving placebo the mean width of the muscle capillary basement membrane increased from 135.9 +/- 9.0 nm (S.E.M.) to 169.3 +/- 9.5 nm (P = 0.01), but in those receiving glipizide the value decreased to a level no different from that in subjects without diabetes: from 152.9 +/- 2.9 to 127.5 +/- 5.1 nm (P = 0.01) [9].
  • PATIENTS--Forty-two NIDDM patients receiving glipizide therapy [10].
  • The concentrations of glipizide that were effective in inhibiting [3H]leucine incorporation into IRI were smaller than those required to inhibit the phosphodiesterase activity in isolated islets of 3-day-old rat pancreas [11].
  • We treated anesthetized Sprague-Dawley rats with the K(ATP) channel openers diazoxide or NNC 55-0118 or the K(ATP) channel closer glipizide [4].
  • In addition, the glipizide treated cats had threefold higher basal and fivefold higher glucose-stimulated plasma IAPP concentrations than insulin-treated cats, suggesting an association between elevated IAPP secretion and islet amyloidosis [3].

Chemical compound and disease context of glipizide


Biological context of glipizide


Anatomical context of glipizide


Associations of glipizide with other chemical compounds

  • Together, these results suggest that both hormones exert their effects on insulin secretion at multiple G-protein-regulated sites including adenylate cyclase and sites distal to the glipizide-binding site on the KATP channel [5].
  • During six months of active drug therapy the mean decrease in fasting serum glucose levels on glipizide was 25 +/- 2% versus 17 +/- 2% on tolbutamide (p less than 0.025) [26].
  • Both antimycin A and glipizide stimulated the efflux of radioactivity, although only the addition of glipizide was accompanied by a stimulation of the insulin release [27].
  • The effects of magnesium hydroxide on the pharmacokinetics and pharmacodynamics of glipizide were studied in eight healthy volunteers in a randomized crossover trial [21].
  • However, clear differences were noted in the early insulin secretion (AUC -15 to 30 min); both repaglinide and glipizide increased secretion in nondiabetic subjects by approximately 61 and 34%, respectively, compared with placebo [28].

Gene context of glipizide

  • Induction of CYP2C9 would explain the increased systemic elimination of glipizide [29].
  • At the end of the study all 4 glipizide-treated cats had islet amyloid deposits, whereas only 1 of 4 insulin-treated cats had detectable amyloid [3].
  • Subjects were switched to glipizide for 2 months (phase I) to confirm failure (fasting plasma glucose [FPG] 12.0 +/- 0.4 mmol/l) and then randomly assigned into three groups: BI-DSU; BI-no DSU; and DSU-no BI [30].
  • In parallel, insulin contents of the islets and the media were determined as well as the rates of glucose-stimulated (pro)insulin biosynthesis. alpha-Ketoisocaproic acid and glipizide were found to stimulate the expression of the 64 kDa/glutamic acid decarboxylase autoantigen and also the rate of insulin secretion [31].
  • In the same rats, glipizide resulted in a significant suppression of glucagon compared with levels in the presence of glucose alone [32].

Analytical, diagnostic and therapeutic context of glipizide

  • INTERVENTION: After a 3-week, single-blind placebo-washout period, participants were randomized to diet and titration with either 5 to 20 mg of glipizide gastrointestinal therapeutic system (GITS) (n = 377) or placebo (n = 192) for 12 weeks [33].
  • Post prandial insulin increments over basal during an oral glucose tolerance test also increased during glipizide, but not tolbutamide therapy [26].
  • RESEARCH DESIGN AND METHODS--In a multicenter, open-label, randomized, two-way crossover study, 132 patients with NIDDM received daily doses of 5, 20, or 40 mg of either glipizide-GITS or immediate-release glipizide for 8 weeks followed by 8 weeks of the alternate formulation [34].
  • Plasma glucose levels decreased significantly after treatment with glipizide [35].
  • Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM. Results of two multicenter, randomized, placebo-controlled clinical trials. The Glipizide Gastrointestinal Therapeutic System Study Group [36].


  1. Diazoxide, glipizide, hypertension and hypoglycaemia. Farr, M.J. Lancet (1976) [Pubmed]
  2. Effect of sulfonylurea treatment on in vivo insulin secretion and action in patients with non-insulin-dependent diabetes mellitus. Greenfield, M.S., Doberne, L., Rosenthal, M., Schulz, B., Widstrom, A., Reaven, G.M. Diabetes (1982) [Pubmed]
  3. A feline model of experimentally induced islet amyloidosis. Hoenig, M., Hall, G., Ferguson, D., Jordan, K., Henson, M., Johnson, K., O'Brien, T. Am. J. Pathol. (2000) [Pubmed]
  4. K(ATP) channels and pancreatic islet blood flow in anesthetized rats: increased blood flow induced by potassium channel openers. Jansson, L., Kullin, M., Karlsson, F.A., Bodin, B., Hansen, J.B., Sandler, S. Diabetes (2003) [Pubmed]
  5. G-proteins and hormonal inhibition of insulin secretion from HIT-T15 cells and isolated rat islets. Seaquist, E.R., Neal, A.R., Shoger, K.D., Walseth, T.F., Robertson, R.P. Diabetes (1992) [Pubmed]
  6. Effects of short-term insulin therapy upon therapeutic response to glipizide. Schwartz, S.L., Fischer, J.S., Kipnes, M.S., Boyle, M. Am. J. Med. (1987) [Pubmed]
  7. Behavioral effects of modulators of ATP-sensitive K+ channels in the rat dorsal pallidum. Amalric, M., Heurteaux, C., Nieoullon, A., Lazdunski, M. Eur. J. Pharmacol. (1992) [Pubmed]
  8. Glipizide treatment with short-term alcohol abuse resulting in subfulminant hepatic failure. Ilario, M.J., Turyan, H.V., Axiotis, C.A. Virchows Arch. (2003) [Pubmed]
  9. Drug-induced reversal of early diabetic microangiopathy. Camerini-Davalos, R.A., Velasco, C., Glasser, M., Bloodworth, J.M. N. Engl. J. Med. (1983) [Pubmed]
  10. Effects of varying carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus. Garg, A., Bantle, J.P., Henry, R.R., Coulston, A.M., Griver, K.A., Raatz, S.K., Brinkley, L., Chen, Y.D., Grundy, S.M., Huet, B.A. JAMA (1994) [Pubmed]
  11. Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin. Garcia, S.D., Jarrousse, C., Rosselin, G. J. Clin. Invest. (1976) [Pubmed]
  12. Effect of glyburide on hepatic glucose metabolism. McGuinness OP; discussion 51S-53S, n.u.l.l., Cherrington, A.D. Am. J. Med. (1990) [Pubmed]
  13. Effect of combination glipizide GITS/metformin on fibrinolytic and metabolic parameters in poorly controlled type 2 diabetic subjects. Cefalu, W.T., Schneider, D.J., Carlson, H.E., Migdal, P., Gan Lim, L., Izon, M.P., Kapoor, A., Bell-Farrow, A., Terry, J.G., Sobel, B.E. Diabetes Care (2002) [Pubmed]
  14. Interaction of ethanol and glipizide in humans. Hartling, S.G., Faber, O.K., Wegmann, M.L., Wåhlin-Boll, E., Melander, A. Diabetes Care (1987) [Pubmed]
  15. A pilot randomized controlled trial of renal protection with pioglitazone in diabetic nephropathy. Agarwal, R., Saha, C., Battiwala, M., Vasavada, N., Curley, T., Chase, S.D., Sachs, N., Semret, M.H. Kidney Int. (2005) [Pubmed]
  16. Individual sulfonylureas and serious hypoglycemia in older people. Shorr, R.I., Ray, W.A., Daugherty, J.R., Griffin, M.R. Journal of the American Geriatrics Society. (1996) [Pubmed]
  17. Different effects of glyburide and glipizide on insulin secretion and hepatic glucose production in normal and NIDDM subjects. Groop, L., Luzi, L., Melander, A., Groop, P.H., Ratheiser, K., Simonson, D.C., DeFronzo, R.A. Diabetes (1987) [Pubmed]
  18. Lipid metabolism in non-insulin-dependent diabetes mellitus: effect of glipizide therapy. Greenfield, M.S., Doberne, L., Rosenthal, M., Vreman, H.J., Reaven, G.M. Arch. Intern. Med. (1982) [Pubmed]
  19. Clinical pharmacology of glipizide. Melander, A., Wåhlin-Boll, E. Am. J. Med. (1983) [Pubmed]
  20. Bioavailability of glipizide and its effect on blood glucose and insulin levels in patients with non-insulin-dependent diabetes. Peterson, C.M., Sims, R.V., Jones, R.L., Rieders, F. Diabetes Care (1982) [Pubmed]
  21. Enhancement of absorption and effect of glipizide by magnesium hydroxide. Kivistö, K.T., Neuvonen, P.J. Clin. Pharmacol. Ther. (1991) [Pubmed]
  22. Selective loss of glucose-induced amplification of insulin secretion in mouse pancreatic islets pretreated with sulfonylurea in the absence of fuels. Urban, K.A., Panten, U. Diabetologia (2005) [Pubmed]
  23. Mechanism of action of the second-generation sulfonylurea glipizide. Lebovitz, H.E., Feinglos, M.N. Am. J. Med. (1983) [Pubmed]
  24. Transfer of glyburide and glipizide into breast milk. Feig, D.S., Briggs, G.G., Kraemer, J.M., Ambrose, P.J., Moskovitz, D.N., Nageotte, M., Donat, D.J., Padilla, G., Wan, S., Klein, J., Koren, G. Diabetes Care (2005) [Pubmed]
  25. Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes. Basu, A., Jensen, M.D., McCann, F., Mukhopadhyay, D., Joyner, M.J., Rizza, R.A. Diabetes Care (2006) [Pubmed]
  26. Glipizide versus tolbutamide, an open trial. Effects on insulin secretory patterns and glucose concentrations. Fineberg, S.E., Schneider, S.H. Diabetologia (1980) [Pubmed]
  27. Efflux of radioactive nucleotides from mouse pancreatic islets prelabelled with 2-3H-adenosine. Welsh, M. Diabetologia (1982) [Pubmed]
  28. Comparison of the effects of three insulinotropic drugs on plasma insulin levels after a standard meal. Cozma, L.S., Luzio, S.D., Dunseath, G.J., Langendorg, K.W., Pieber, T., Owens, D.R. Diabetes Care (2002) [Pubmed]
  29. Effects of rifampin on the pharmacokinetics and pharmacodynamics of glyburide and glipizide. Niemi, M., Backman, J.T., Neuvonen, M., Neuvonen, P.J., Kivistö, K.T. Clin. Pharmacol. Ther. (2001) [Pubmed]
  30. Bedtime insulin/daytime glipizide. Effective therapy for sulfonylurea failures in NIDDM. Shank, M.L., Del Prato, S., DeFronzo, R.A. Diabetes (1995) [Pubmed]
  31. Expression of the 64 kDa/glutamic acid decarboxylase rat islet cell autoantigen is influenced by the rate of insulin secretion. Björk, E., Kämpe, O., Andersson, A., Karlsson, F.A. Diabetologia (1992) [Pubmed]
  32. Islet allografts in the cryptorchid testes of spontaneously diabetic BB/Wor dp rats: response to glucose, glipizide, and arginine. Whittington, K.B., Solomon, S.S., Lu, Z.N., Selawry, H.P. Endocrinology (1991) [Pubmed]
  33. Health economic benefits and quality of life during improved glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled, double-blind trial. Testa, M.A., Simonson, D.C. JAMA (1998) [Pubmed]
  34. Comparative efficacy of a once-daily controlled-release formulation of glipizide and immediate-release glipizide in patients with NIDDM. Berelowitz, M., Fischette, C., Cefalu, W., Schade, D.S., Sutfin, T., Kourides, I.A. Diabetes Care (1994) [Pubmed]
  35. Effect of glipizide on insulin secretion and insulin metabolism in obese type II diabetic patients. Bonora, E., Pisani, F., Micciolo, R., Corgnati, A., Muggeo, M. Diabetes Care (1987) [Pubmed]
  36. Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM. Results of two multicenter, randomized, placebo-controlled clinical trials. The Glipizide Gastrointestinal Therapeutic System Study Group. Simonson, D.C., Kourides, I.A., Feinglos, M., Shamoon, H., Fischette, C.T. Diabetes Care (1997) [Pubmed]
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