Efficacy of pharmacological inhibition of intestinal saccharases in patients with diabetes mellitus type 2 and/or visceral obesity


Cite item

Full Text

Abstract

Inhibitors of intestinal enzymes regulate carbohydrate metabolism reducing glycemic index, glycemic load of food and postprandial glycemia which is a prognostic factor of DM2-related cardiovascular complications and death. This class of drugs was proposed for DM2 treatment in 1970s but still holds perspectives. The article gives a detailed description of the mechanism of action, efficacy and safety of inhibitors of alpha-glucosidase and alpha-amilase in experimental and clinical controlled trials.

About the authors

Aleksandr Sergeevich Ametov

Lyudmila Leonidovna Kamynina

Email: petrology@yandex.ru

A S Ametov

Russian Medical Academy of Postgraduate Education, Moscow

Russian Medical Academy of Postgraduate Education, Moscow

L L Kamynina

Russian Medical Academy of Postgraduate Education, Moscow

Russian Medical Academy of Postgraduate Education, Moscow

References

  1. Wachters-Hagedoorn R. E., Priebe M. G., Heimweg J. A. et al. Low-dose acarbose does not delay digestion of starch but reduces its bioavailability. Diabet. Med. 2007; 24(6): 600-606.
  2. Vega-López S., Mayol-Kreiser S. N. Use of the glycemic index for weight loss and glycemic control: A review of recent evidence. Curr Diabet. Rep. 2009; 9: 379-388.
  3. Чазова И. Е., Мычка В. Б. Первые результаты Российской программы "Апрель" (Эффективность применения акарбозы у пациентов с нарушенной толерантностью к глюкозе и артериальной гипертонией). Ожирение и метаболизм 2005; 1(3): 13-21.
  4. Udani J. K., Singh B. B., Barrett M. L., Preuss H. G. Lowering the glycemic index of white bread using a white bean extract. Nutr. J. 2009; 8: 52.
  5. Johnson S. T., Bell G. J., McCargar L. J. et al. Improved cardiovascular health following a progressive walking and dietary intervention for type 2 diabetes. Diabet. Obes. Metab. 2009; 11(9): 836-843.
  6. Jenkins D. J. A., Kendall C. W. C., McKeown-Eyssen G. et al. Diet on type 2 diabetes: a randomized trial effect of a low glycemic index or a high cereal fiber. J. A. M. A. 2008; 300(23): 2742-2753.
  7. Wolever T. M., Gibbs A. L., Mehling C. et al. The Canadian Trial of Carbohydrates in Diabetes (CCD), a 1-y controlled trial of low-glycemic-index dietary carbohydrate in type 2 diabetes: no effect on glycated hemoglobin but reduction in C-reactive protein. Am. J. Clin. Nutr. 2008; 87(1): 114-125.
  8. Rempel B. P., Withers S. G. Covalent inhibitors of glycosidases and their applications in biochemistry and biology. Glycobiology 2008; 18(8): 570-586.
  9. Sevcik J., Hostinovä E., Solovicovä A. et al. Structure of the complex of a yeast glucoamylase with acarbose reveals the presence of a raw starch binding site on the catalytic domain. FEBS J. 2006; 273(10): 2161-2171.
  10. Schnell O., Mertes G., Standl E. Acarbose-Insulin Combination Study Group. Acarbose and metabolic control in patients with type 2 diabetes with newly initiated insulin therapy. Diabet. Obes. Metab. 2007; 9(6): 853-858.
  11. Chiasson J. L. Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial. Endocr. Pract. 2006; 12(Suppl. 1): 25-30.
  12. Hanefeld M., Karasik A., Koehler C. et al. Metabolic syndrome and its single traits as risk factors for diabetes in people with impaired glucose tolerance: the STOP-NIDDM trial. Diabet. Vasc. Dis. Res. 2009; 6(1): 32-37.
  13. Задионченко В. С., Адашева Т. В., Демичева О. Ю., Порывкина О. Н. Метаболический синдром: терапевтические возможности и перспективы. Consilium Medicum 2005; 7(9): 725-733.
  14. Tuomilehto J., Lindstróm J., Hellmich M. et al. Development and validation of a risk-score model for subjects with impaired glucose tolerance for the assessment of the risk of type 2 diabetes mellitus - The STOP-NIDDM risk-score. Diabet. Res. Clin. Pract. 2010; 87(2): 267-274.
  15. Pan C. Y. Reducing the risk of type 2 diabetes: early identification of high-risk individuals and treatment with acarbose. Curr. Diabet. Rev. 2007; 3(2): 141-148.
  16. Nijpels G., Boorsma W., Dekker J. M. et al. A study of the effects of acarbose on glucose metabolism in patients predisposed to developing diabetes: the Dutch acarbose intervention study in persons with impaired glucose tolerance (DAISI). Diabet. Metab. Res. Rev. 2008; 24(8): 611-616.
  17. Сахарова Н. С., Мышляева Т. О., Стародубова А. В., Кисляк О. А. Профилактика сахарного диабета 2 типа и сердечно-сосудистых осложнений у пациентов с предиабетом. Лечеб. дело 2008; 6(4): 57-62.
  18. Zeymer U. Cardiovascular benefits of acarbose in impaired glucose tolerance and type 2 diabetes. Int. J. Cardiol. 2006; 107(1): 11-20.
  19. Hanefeld M., Schaper F. Acarbose: oral anti-diabetes drug with additional cardiovascular benefits. Expert Rev. Cardiovasc. Ther. 2008; 6(2): 153-163.
  20. Мычка В. Б., Чазова И. Е. Медикаментозная коррекция нарушений углеводного обмена: снижение риска сердечно-сосудистых осложнений. Consilium Medicum 2008; 10(11): 57-62.
  21. Bävenholm P. N., Efendic S. Postprandial hyperglycaemia and vascular damage - the benefits of acarbose. Diabet. Vasc. Dis. Res 2006; 3(2): 72-79.
  22. Yamagishi S., Matsui T., Ueda S. et al. Clinical utility of acarbose, an alpha-glucosidase inhibitor in cardiometabolic disorders. Curr. Drug Metab. 2009; 10(2): 159-163.
  23. Rosak C., Mertes G. Effects of acarbose on proinsulin and insulin secretion and their potential significance for the intermediary metabolism and cardiovascular system. Curr. Diabet. Rev. 2009; 5(3): 157-164.
  24. Shimabukuro M., Higa N., Chinen I. et al. Effects of a single administration of acarbose on postprandial glucose excursion and endothelial dysfunction in type 2 diabetic patients: a randomized crossover study. J. Clin. Endocrinol. 2006; 91(3): 837-842.
  25. Wagner H., Degerblad M., Thorell A. et al. Combined treatment with exercise training and acarbose improves metabolic control and cardiovascular risk factor profile in subjects with mild type 2 diabetes. Diabet. Care 2006; 29(7): 1471-1477.
  26. Hanefeld M., Schaper F., Koehler C. et al. Effect of acarbose on postmeal mononuclear blood cell response in patients with early type 2 diabetes: the AI(I)DA study. Horm. Metab. Res. 2009; 41(2): 132-136.
  27. Shimabukuro M., Higa N., Chinen I. et al. Effects of a single administration of acarbose on postprandial glucose excursion and endothelial dysfunction in type 2 diabetic patients: a randomized crossover study. J. Clin. Endocrinol. 2006; 91(3): 837-842.
  28. Kadowaki T., Yamauchi T., Kubota N. et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J. Clin. Invest. 2006; 116(7): 1784-1792.
  29. Pérez C., Fernändez-Agulló T., De Solis A. J. et al. Effects of chronic acarbose treatment on adipocyte insulin responsiveness, serum levels of leptin and adiponectin and hypothalamic NPY expression in obese diabetic Wistar rats. Clin. Exp. Pharmacol. Physiol. 2008; 35(3): 256-261.
  30. Ochiai H., Ooka H., Shida C. et al. Acarbose treatment increases serum total adiponectin levels in patients with type 2 diabetes. Endocr. J. 2008; 55(3): 549-556.
  31. Santilli F., Formoso G., Sbraccia P. et al. Postprandial hyperglycemia is a determinant of platelet activation in early type 2 diabetes mellitus. J. Thromb. Haemost. 2010; 8(4): 828-837.
  32. Shimazu T., Inami N., Satoh D. et al. Effect of acarbose on platelet-derived microparticles, soluble selectins, and adiponectin in diabetic patients. J. Thromb. Thrombolys. 2009; 28(4): 429-435.
  33. Аронов Д. М. Двойное профилактическое действие акарбозы - ингибитора альфа-глюкозидазы. Фарматека 2004; 10(5): 39-43.
  34. Hücking K., Kostic Z., Pox C. et al. Alpha-glucosidase inhibition (acarbose) fails to enhance secretion of glucagon-like peptide 1 (7-36 amide) and to delay gastric emptying in Type 2 diabetic patients. Diabet. Med. 2005; 22(4): 470-476.
  35. Анциферов М. Б., Дорофеева Л. Г., Демидов Н. А. Эффективность применения акарбозы у пациентов с сахарным диабетом типа 2. Фарматека 2006; 12(17): 79-84.
  36. Майоров А. Ю., Урбанова К. А. Современные сахароснижающие средства в лечении сахарного диабета 2-го типа. Consilium Medicum 2007; 9(9): 5-13.
  37. Мкртумян А. М. Комбинированная терапия акарбозой с метформином: успешный контроль гликемии и предупреждение истощения инсулярного аппарата. Consilium Medicum 2009; 11(12): 25-28.
  38. Древаль А. В., Мисникова И. В., Барсуков И. А. Лечение ранних нарушений углеводного обмена. Лечащий врач 2008; 11(10): 36-39.
  39. Демидова И. Ю., Чазова Т. Е. Использование ингибиторов альфа-глюкозидаз для профилактики сахарного диабета 2 у лиц с нарушенной толерантностью к глюкозе. Фарматека. 2003; 10(3): 26-30.
  40. Geisthóvel F., Frorath B., Brahant G. Acarbose reduces elevated testosterone serum concentrations in hyperinsulinaemic premenopausal women: a pilot study. Hum. Reprod. 1996; l1(11): 2377-2381.
  41. Sónmez A. S., Yasar L., Savan K. et al. Comparison of the effects of acarbose and metformin use on ovulation rates in clomiphene citrate-resistant polycystic ovary syndrome. Hum. Reprod. 2005; 20(1): 175-179.
  42. Tügrul S., Kutlu T., Pekin O. et al. Clinical, endocrine, and metabolic effects of acarbose: a alpha-glucosidase inhibitor, in overweight and nonoverweight patients with polycystic ovarian syndrome. Fertil. and Steril. 2008; 90(4): 1144-1148.
  43. Penna I. A. A., Canella P. R. B., Reis R. M. ct al. Acarbose in obese patients with polycystic ovarian syndrome: a double-blind, randomized, placebo-controlled study. Hum. Reprod. 2005; 20(9): 2396-2401.
  44. Kircher C., Smith K. P. Acarbose for polycystic ovary syndrome. Ann. Pharmacother. 2008; 42(6): 847-851.
  45. Penna A. I., Canella P. R., Vieira C. S. et al. Cardiovascular risk factors are reduced with a low dose of acarbose in obese patients with polycystic ovary syndrome. Fertil. and Steril. 2007; 88(2): 519-522.
  46. Mühlhauser I. Voglibose for prevention of type 2 diabetes mellitus. Lancet 2009; 374(9688): 448.
  47. Chen X., Zheng A., Shen Y. Voglibose (Basen®, AO-128), one of the most important α-glucosidase inhibitors. Curr. Med. Chem. 2006; 13: 109-116.
  48. Negishi M., Shimomura K., Proks P. et al. Alpha glucosidase inhibitor voglibose can prevent pioglitazone-induced body weight gain in type 2 diabetic patients. Br. J. Clin. Pharmacol. 2008; 66(2): 318-319.
  49. Moritoh Y., Takeuchi K., Hazama M. Chronic administration of voglibose, an alpha-glucosidase inhibitor, increases active glucagon-like peptide-1 levels by increasing its secretion and decreasing dipeptidyl peptidase-4 activity in ob/ob mice. J. Pharmacol. Exp. Ther. 2009; 329(2): 669-676.
  50. Yamazaki K., Inoue T., Yasuda N. et al. Comparison of efficacies of a dipeptidyl peptidase IV inhibitor and alpha-glucosidase inhibitors in oral carbohydrate and meal tolerance tests and the effects of their combination in mice. J. Pharmacol. Sci. 2007; 104(1): 29-38.
  51. Arakawa M., Ebato C., Mita T. et al. Miglitol suppresses the postprandial increase in interleukin 6 and enhances active glucagon-like peptide 1 secretion in viscetally obese subjects. Metabolism 2008; 57(9): 1299-1306.
  52. Aoki K., Nakamura A., Ito S. et al. Administration of miglitol until 30 min after the start of a meal is effective in type 2 diabetic patients. Diabet. Res. Clin. Pract. 2007; 78(1): 30-33.
  53. Aoki K., Nakajima S., Nezu U. et al. Comparison of pre- vs. postmeal administration of miglitol for 3 month in type 2 diabetic patients. Diabet. Obes. Metab. 2008; 10(10): 970-972.
  54. Narita T., Katsuura Y., Sato T. et al. Miglitol induces prolonged and enhanced glucagon-like peptide-l and reduced gastric inhibitory polypeptide responses after ingestion of a mixed meal in Japanese Type 2 diabetic patients. Diabet. Med. 2009; 26(2): 187-188.
  55. Voss A. A., Dr'ez-Sampedro A., Hirayama B. A. et al. Imino sugars are potent agonists of the human glucose sensor SGLT3. Mol. Pharmacol 2007; 71(2): 628-634.
  56. Fairchild T. J. Protection of muscle membrane excitability during cycling in humans: a role for SGLT3? J. Appl. Physiol. 2008; 104(1): 315.
  57. Obiro W. C., Zhang T., Jiang B. The nutraceutical role of the Phaseolus vulgaris alpha-amylase inhibitor. Br. J. Nutr. 2008; 100(1): 1-12.
  58. Yang M. Y., Zhang X. Q., Ma Y. et al. Purification and partial characterization of a glycoprotein alpha-amylase inhibitor from white kidney bean (Phaseolus vulgaris L). J. Food Biochem. 2008; 32: 72-84.
  59. Kotowaroo M. I., Mahomoodally M. F., Gurib-Fakim A., Subratty A. H. Screening of traditional antidiabetic medicinal plants of Mauritius for possible α-amylase inhibitory effects in vitro. Phytother. Res. 2006; 20(3): 228-231.
  60. Heo S. J., Hwang J. Y., Choi J. I. et al. Diphlorethohydroxycarmalol isolated from Ishige okamurae, a brown algae, a potent alpha-glucosidase and alpha-amylase inhibitor, alleviates postprandial hyperglycemia in diabetic mice. Eur. J. Pharmacol. 2009; 615 (1-3): 252-256.
  61. Ali H., Houghton P. J., Soumyanath A. Alpha-amylase inhibitory activity of some Malaysian plants used to treat diabetes; with particular reference to Phyllanthus amarus. J. Ethnopharmacol. 2006; 107(3): 449-455.
  62. Tsujita T., Takaku T., Suzuki T. Chestnut astringent skin extract, an alpha-amylase inhibitor, retards carbohydrate absorption in rats and humans. J. Nutr. Sci. Vitaminol. 2008; 54(1): 82-88.
  63. Kwon Y. I., Apostolidis E., Shetty K. Inhibitory potential of wine and tea against α-amylase and α-glucosidase for management of hyperglycemia linked to type 2 diabetes. J. Food Biochem. 2008; 32: 15-31.
  64. Lo Piparo E., Scheib H., Frei N. et al. Flavonoids for controlling starch digestion: structural requirements for inhibiting human alpha-amylase. J. Med. Chem. 2008; 51(12): 3555-3561.
  65. Hasani-Ranjbar S., Nayebi N., Larijani B., Abdollahi M. A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity. Wld J. Castroenterol. 2009: 15(25): 3073-3085.
  66. Boniglia C., Carratü B., Di Stefano S. et al. Lectins, trypsin and α-amylase inhibitors in dietary supplements containing Phaseolus vulgaris. Eur. Food Res. Technol. / Z. Lebensmittel- Untersuch. -Forsch. A. 2007; 227(3): 689-693.
  67. Harikumar K. B., Jesil A. M., Sabu M. C., Kuttan R. Preliminary assessment of the acute and subchronic toxicity profile of phase 2: an alpha-amylase inhibitor. Int. J. Toxicol. 2005; 24(2): 95-102.
  68. Chokshi D. Toxicity studies of Blockal, a dietary supplement containing Phase 2 starch neutralizer (Phase 2), a standardized extract of the common white kidney bean (Phaseolus vulgaris). Int. J. Toxicol. 2006; 25(5): 361-371.
  69. Preuss H. G., Echard B., Bagchi D., Stohs S. Inhibition by natural dietary substances of gastrointestinal absorption of starch and sucrose in rats and pigs: 1. Acute studies. Int. J. Med. Sci. 2007; 4(4): 196-202.
  70. Preuss H. G., Echard B., Bagchi D., Stohs S. Inhibition by natural dietary substances of gastrointestinal absorption of starch and sucrose in rats 2. Subchronic studies. Int. J. Med. Sci. 2007; 4(4): 209-215.
  71. Tormo M. A., Gil-Exojo I., Romero de Tejada A., Campillo J. E. White bean amylase inhibitor administered orally reduces glycaemia in type 2 diabetic rats. Br. J. Nutr. 2006; 96(3); 539- 544.
  72. Fantini N., Cabras C., Lobina C. et al. Reducing effect of a Phaseolus vulgaris dry extract on food intake, body weight, and glycemia in rats. J. Agric. Food Chem. 2009; 57(19): 9316- 9323.
  73. Udani J., Singh B. B. Blocking carbohydrate absorption and weight loss: a clinical trial using a proprietary fractionated white bean extract. Altern. Ther. Hlth Med. 2007; 13(4): 32- 37.
  74. Celleno L., Tolaini M. V., D'Amore A. et al. A dietary supplement containing standardized Phaseolus vulgaris extract influences body composition of overweight men and women. Int. J. Med. Sci. 2007; 4(1): 45-52.
  75. Udani J., Hardy M., Madsen D. C. Blocking carbohydrate absorption and weight loss: a clinical trial using Phase 2TM brand proprietary fractionated white bean extract. Altern. Med. Rev. 2004; 9(1): 63-69.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2011 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

 © 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies