Subscribe to RSS
DOI: 10.1055/s-0032-1304563
Anorexigenic Effects of Miglitol in Concert with the Alterations of Gut Hormone Secretion and Gastric Emptying in Healthy Subjects
Publication History
received 01 October 2011
accepted 19 January 2012
Publication Date:
20 February 2012 (online)
![](https://www.thieme-connect.de/media/hmr/201204/lookinside/thumbnails/10.1055-s-0032-1304563-1.jpg)
Abstract
Although the α-glucosidase inhibitor miglitol (MG) has been reported to have anorexigenic effects, the mechanism remains to be elucidated. The objective of this study was to explore the effects of MG on appetite in relation to concomitant changes in postprandial gut hormone levels. This randomized open-label crossover study included 20 healthy volunteers. The effects of 50 mg MG on glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin levels were assessed in conjunction with a simultaneous determination of appetite scores using visual analogue scales (VAS) over 3 h after the ingestion of a 592 kcal test cookie. Additionally, the gastric emptying rate (GER) was measured using breath 13CO2 appearance in 10 subjects. 12 subjects were administered 50 mg MG thrice a day for 1 week, and alterations of the gut hormone levels and the VAS scores for appetite were evaluated. MG pre-administration resulted in a significant enhancement of GLP-1 and PYY responses induced by the cookie ingestion. Following MG administration, ghrelin level declined at 1 h, with a persistent suppression during the postprandial phase in contrast to the restoration to the basal level without MG. Furthermore, MG pre-administration suppressed appetite and maintained satiety evaluated using a VAS rating with concomitant inhibition of GER after cookie ingestion. One-week administration of MG did not influence either gut hormone levels before a meal or VAS rating during a whole day. These observations suggest that MG exerts an anorexigenic effects with concomitant alterations of gut hormone secretions and gastric emptying after meal ingestion.
-
References
- 1 Ranganath L, Norris F, Morgan L, Wright J, Marks V. Delayed gastric emptying occurs following acarbose administration and is a further mechanism for its anti-hyperglycaemic effect. Diabet Med 1998; 15: 120-124
- 2 Goke B, Fuder H, Wieckhorst G, Theiss U, Stridde E, Littke T, Kleist P, Arnold R, Lucker PW. Voglibose (AO-128) is an efficient alpha-glucosidase inhibitor and mobilizes the endogenous GLP-1 reserve. Digestion 1995; 56: 493-501
- 3 Herrmann C, Goke R, Richter G, Fehmann HC, Arnold R, Goke B. Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients. Digestion 1995; 56: 117-126
- 4 Hameed S, Dhillo WS, Bloom SR. Gut hormones and appetite control. Oral Dis 2009; 15: 18-26
- 5 Naslund E, Gutniak M, Skogar S, Rossner S, Hellstrom PM. Glucagon-like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. Am J Clin Nutr 1998; 68: 525-530
- 6 Turton MD, O’Shea D, Gunn I, Beak SA, Edwards CM, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD, Wilding JP, Smith DM, Ghatei MA, Herbert J, Bloom SR. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 1996; 379: 69-72
- 7 Lee A, Patrick P, Wishart J, Horowitz M, Morley JE. The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics. Diabetes Obes Metab 2002; 4: 329-335
- 8 Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 1985; 89: 1070-1077
- 9 Grandt D, Schimiczek M, Beglinger C, Layer P, Goebell H, Eysselein VE, Reeve Jr JR. Two molecular forms of peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1-36 and PYY 3-36. Regul Pept 1994; 51: 151-159
- 10 Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 2002; 418: 650-654
- 11 Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, Matsukura S, Kangawa K, Nakazato M. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 2000; 141: 4255-4261
- 12 Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402: 656-660
- 13 Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001; 50: 1714-1719
- 14 Inui A, Asakawa A, Bowers CY, Mantovani G, Laviano A, Meguid MM, Fujimiya M. Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ. FASEB J 2004; 18: 439-456
- 15 Alberti KG, Zimmet P, Shaw J. Metabolic syndrome – a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 2006; 23: 469-480
- 16 Harano Y, Miyawaki T, Nabiki J, Shibachi M, Adachi T, Ikeda M, Ueda F, Nakano T. Development of cookie test for the simultaneous determination of glucose intolerance, hyperinsulinemia, insulin resistance and postprandial dyslipidemia. Endocr J 2006; 53: 173-180
- 17 Ghoos YF, Maes BD, Geypens BJ, Mys G, Hiele MI, Rutgeerts PJ, Vantrappen G. Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test. Gastroenterology 1993; 104: 1640-1647
- 18 Perri F, Bellini M, Portincasa P, Parodi A, Bonazzi P, Marzio L, Galeazzi F, Usai P, Citrino A, Usai-Satta P. (13)C-octanoic acid breath test (OBT) with a new test meal (EXPIROGer): Toward standardization for testing gastric emptying of solids. Dig Liver Dis 2010; 42: 549-553
- 19 Stubbs RJ, Hughes DA, Johnstone AM, Rowley E, Reid C, Elia M, Stratton R, Delargy H, King N, Blundell JE. The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings. Br J Nutr 2000; 84: 405-415
- 20 Moser EB. Repeated measures modeling with PROC mixed, In SUGI 29. In: Owen D. (ed.). Repeated measures modeling with PROC mixed. Montreal. 2004. 188-29. 1-19
- 21 Fukase N, Takahashi H, Manaka H, Igarashi M, Yamatani K, Daimon M, Sugiyama K, Tominaga M, Sasaki H. Differences in glucagon-like peptide-1 and GIP responses following sucrose ingestion. Diabetes Res Clin Pract 1992; 15: 187-195
- 22 Qualmann C, Nauck MA, Holst JJ, Orskov C, Creutzfeldt W. Glucagon-like peptide 1 (7-36 amide) secretion in response to luminal sucrose from the upper and lower gut. A study using alpha-glucosidase inhibition (acarbose). Scand J Gastroenterol 1995; 30: 892-896
- 23 Seifarth C, Bergmann J, Holst JJ, Ritzel R, Schmiegel W, Nauck MA. Prolonged and enhanced secretion of glucagon-like peptide 1 (7-36 amide) after oral sucrose due to alpha-glucosidase inhibition (acarbose) in Type 2 diabetic patients. Diabet Med 1998; 15: 485-491
- 24 Hucking K, Kostic Z, Pox C, Ritzel R, Holst JJ, Schmiegel W, Nauck MA. 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: 470-476
- 25 DeLeon MJ, Chandurkar V, Albert SG, Mooradian AD. Glucagon-like peptide-1 response to acarbose in elderly type 2 diabetic subjects. Diabetes Res Clin Pract 2002; 56: 101-106
- 26 Toft-Nielsen MB, Damholt MB, Madsbad S, Hilsted LM, Hughes TE, Michelsen BK, Holst JJ. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001; 86: 3717-3723
- 27 Requejo F, Uttenthal LO, Bloom SR. Effects of alpha-glucosidase inhibition and viscous fibre on diabetic control and postprandial gut hormone responses. Diabet Med 1990; 7: 515-520
- 28 Karczewska-Kupczewska M, Straczkowski M, Adamska A, Nikolajuk A, Otziomek E, Gorska M, Kowalska I. Increased suppression of serum ghrelin concentration by hyperinsulinemia in women with anorexia nervosa. Eur J Endocrinol 2010; 162: 235-239
- 29 Saad MF, Bernaba B, Hwu CM, Jinagouda S, Fahmi S, Kogosov E, Boyadjian R. Insulin regulates plasma ghrelin concentration. J Clin Endocrinol Metab 2002; 87: 3997-4000
- 30 Kirchner H, Tong J, Tschop MH, Pfluger PT. Ghrelin and PYY in the regulation of energy balance and metabolism: lessons from mouse mutants. Am J Physiol Endocrinol Metab 2010; 298: E909-E919
- 31 Witte AB, Gryback P, Holst JJ, Hilsted L, Hellstrom PM, Jacobsson H, Schmidt PT. Differential effect of PYY1-36 and PYY3-36 on gastric emptying in man. Regul Pept 2009; 158: 57-62
- 32 Anini Y, Hansotia T, Brubaker PL. Muscarinic receptors control postprandial release of glucagon-like peptide-1: in vivo and in vitro studies in rats. Endocrinology 2002; 143: 2420-2426
- 33 Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, Kim HH, Xu X, Chan SL, Juhaszova M, Bernier M, Mosinger B, Margolskee RF, Egan JM. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci USA 2007; 104: 15069-15074
- 34 Lee S, Yabe D, Nohtomi K, Takada M, Morita R, Seino Y, Hirano T. Intact glucagon-like peptide-1 levels are not decreased in Japanese patients with type 2 diabetes. Endocr J 2010; 57: 119-126
- 35 Kirchner H, Gutierrez JA, Solenberg PJ, Pfluger PT, Czyzyk TA, Willency JA, Schurmann A, Joost HG, Jandacek RJ, Hale JE, Heiman ML, Tschop MH. GOAT links dietary lipids with the endocrine control of energy balance. Nat Med 2009; 15: 741-745
- 36 Julious SA. Sample sizes for clinical trials with normal data. Stat Med 2004; 23: 1921-1986