AccScience Publishing / GTM / Online First / DOI: 10.36922/gtm.6501
Submit to GTM
Cite this article
8
Download
199
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Luminal α-glucosidase inhibition improves insulin sensitivity and modulates glycemic and lipid profiles in obese rats with type 2 diabetes mellitus

Orien L. Tulp1* ,  Syed A. A. Rizvi2,3
Show Less
1 Department of Medicine, University of Science, Arts and Technology, Montserrat, British West Indies, United Kingdom
2 Department of Biomedical Sciences, College of Biomedical Sciences, Larkin University, Miami, Florida, United States of America
3 Division of Clinical and Translational Research, Larkin Community Hospital, Miami, Florida, United States of America
Global Translational Medicine, 6501 https://doi.org/10.36922/gtm.6501
Submitted: 22 November 2024 | Revised: 5 February 2025 | Accepted: 21 February 2025 | Published: 26 March 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

Atherogenic plasma lipid and glycemic profiles are commonly observed in obesity and adult-onset type 2 diabetes mellitus (T2DM) and may improve following therapeutic intervention. The effects of the luminal α-glucosidase inhibitor miglitol (MIG) on carbohydrate digestion and plasma lipid profiles were evaluated in adult male obese spontaneously hypertensive and diabetes-prone/Ntul//-cp rats, a genetic model that develops early-onset obesity and T2DM independently of diet. Rats were fed either a nutritionally complete diet (formulated by the United States Department of Agriculture) containing 54% sucrose as the carbohydrate component (control) or the same diet supplemented with MIG at 150 mg/kg of diet admixture ad libitum for <8 weeks. MIG treatment resulted in a ~15% decrease in energy intake (p<0.05), net weight gain (p<0.05), and a 14% decrease in adiposity (p<0.05), along with significant decreases in fasting glucose, insulin, and glycated hemoglobin (p<0.05). In addition, MIG reduced the glucose area under the curve by 20% (p<0.05), triglycerides by 15% (p<0.05), and the total cholesterol, α-lipoprotein (low-density lipoprotein), and β-lipoprotein (high-density lipoprotein) fractions by 20% (p<0.05, all comparisons). MIG regimen also led to decreases in liver glucokinase, malic enzyme, and glucose-6-phosphate dehydrogenase (p<0.05). In conclusion, these results suggest that therapeutic α-glucosidase inhibition through MIG improves multiple insulin-related atherogenic parameters and may serve as a useful adjunct in the long-term clinical management of plasma lipid and glycemic profiles in the glucose-intolerant states of obesity and T2DM.

Keywords
Obesity
Type 2 diabetes mellitus
Miglitol
α-glucosidase activity
Glycemic parameters
Lipid profiles
Liver enzymes
spontaneously hypertensive and diabetes-prone/Ntul//-cp rat
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
References
  1. Kelly T, Yang CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond). 2008;32(9):1431-1437. doi: 10.1038/ijo.2008.102

 

  1. Aggarwal R, Ostrominski JW, Vaduganathan M. Prevalence of cardiovascular-kidney-metabolic syndrome stages in US adults, 2011-2020. JAMA. 2024;331:1858-1860. doi: 10.1001/jama.2024.6892

 

  1. Njoloma I, Lewis N, Sainvil F, et al. A primer on hypertension and the racial/ethnic disparities in diagnosis and management. A comprehensive overview. Int J Family Clin Med. 2021;5(6):229-239.

 

  1. Available from: https://www.cdc.gov/diabetes/php/data-research/index.html; https://www.who.int/news-room/fact-sheets/detail/diabetes [Last accessed on 2025 Mar 25].

 

  1. Soták M, Clark M, Suur BE, Börgeson E. Inflammation and resolution in obesity. Nat Rev Endocrinol. 2025;21:45-61. doi: 10.1038/s41574-024-01047-y

 

  1. Wiley CD, Campisi J. The metabolic roots of senescence: mechanisms and opportunities for intervention. Nat Metab. 2021;3(10):1290-1301. doi: 10.1038/s42255-021-00483-8

 

  1. Malik A, Erginkaya Z, Erten H, editors. Health and Safety Aspects of Food Processing Technologies. Ch. 1-23. Germany: Springer Publications; 2020. doi: 10.1007/978-3-030-24903-8

 

  1. Bray GA. Energy and fructose from beverages sweetened with sugar or high-fructose corn syrup pose a health risk for some people. Adv Nutr. 2013;4:220-225. doi: 10.3945/an.112.002816

 

  1. Assefa ST, Yang EY, Chae SY, et al. Alpha glucosidase inhibitory activities of plants with focus on common vegetables. Plants (Basel). 2020;9(1):2-19. doi: 10.3390/plants9010002

 

  1. Douard V, Ferraris RP. Regulation of the fructose transporter GLUT5 in health and disease. Am J Physiol Endocrinol Metab. 2008;295:E227-E237. doi: 10.1152/ajpendo.90245.2008

 

  1. Leonhardt W, Hanefeld M, Fischer S, Schulze J. Efficacy of alpha-glucosidase inhibitors on lipids in NIDDM subjects with moderate hyperlipidemia. Eur J Clin Invest. 1994;24 Suppl 3:45-49. doi: 10.1111/j.1365-2362.1994.tb02256.x

 

  1. Monami M, Vitale V, Ambrosio ML, et al. Effects on lipid profile of dipeptidyl peptidase 4 inhibitors, pioglitazone, acarbose, and sulfonylureas: Meta-analysis of placebo-controlled trials. Adv Ther. 2012;29(9):736-746. doi: 10.1007/s12325-012-0045-5

 

  1. Leonhardt W, Hanefeld M, Fischer S, Schulze J, Spengler M. Beneficial effects on serum lipids in noninsulin dependent diabetics by acarbose treatment. Arzneimittelforschung. 1991;41(7):735-738.

 

  1. Hoffmann J, Spengler M. Efficacy of 24-week monotherapy with acarbose, metformin, or placebo in dietary-treated NIDDM patients: The Essen-II study. Am J Med. 1997;103(6):483-490. doi: 10.1016/s0002-9343(97)00252-0

 

  1. Chiasson JL, Naditch L, Miglitol Canadian University Investigator Group. The synergistic effect of miglitol plus metformin combination therapy in the treatment of type 2 diabetes. Diabetes Care. 2001;24:989-994. doi: 10.2337/diacare.24.6.989

 

  1. Tulp OL. Biometry, adiposity and mechanism of protein sparing growth in congenic preobese LA/Ntul//-cp rats. Br J Healthc Med Res. 2023;10:364-374. doi: 10.14738/bjhmr.103.14969

 

  1. Granner DK, Mayes PA, Murray RK, et al. Harpers Illustrated Biochemistry. New York: McGraw-Hill Publications; 2012.

 

  1. Tulp OL. Characteristics of thermogenesis, obesity, and longevity in the LA/Ntul//–cp rat. ILAR J. 1990;32(3):32-39.

 

  1. Greenhouse DD. New Models of genetically obese rats for studies of diabetes, heart disease, and complications of obesity. ILAR J. 1990;32(3):1-3.

 

  1. Hansen CT. The development of the SHR/N and LA/N-cp rat strains. In: NER Models of Genetically Obese Rats for Studies in Diabetes, Heart Disease, and Complications of Obesity. Bethesda, MD, USA: NIH Publication, Division of Research Services, Veterinary Resources Branch; 1988. p. 7-10.

 

  1. Jing AI, Wang N, Yang M, Du ZM, Zhang YC, Yang BF. Development of Wistar rat model of insulin resistance. World J Gastroenterol. 2005;11(24):3675-3679. doi: 10.3748/wjg.v11.i24.3675

 

  1. Ikeda H, Matsuo T. A new genetically obese hyperglycemic rat (Wistar fatty). Diabetes. 1981;30:1045-1050. doi: 10.2337/diabetes.30.12.1045

 

  1. Zucker LM, Zucker TF. Fatty, a new mutation in the rat. J Heredity. 1961;52(6):275-278. doi: 10.1093/oxfordjournals.jhered.a107093

 

  1. Peterson RG, Little LA, Neel MA. WKY Fatty rat as a model of obesity and non-insulin-dependent diabetes mellitus. ILAR J. 1990;32(3):13-15. doi: 10.1093/ilar.32.3.13

 

  1. Russell JC, Koeslag DG. Jcr: LA-corpulent Rat: A strain with spontaneous vascular and myocardial disease. ILAR J. 1990;32(3):27-32. doi: 10.1093/ilar.32.3.27

 

  1. Wu-Peng XS, Chua SC, Okada N, Liu SM, Nicolson M, Leibel RL. Phenotype of the obese Koletsky (f) rat due to Tyr763Stop mutation in the extracellular domain of the leptin receptor (Lepr): Evidence for deficient plasma-to-CSF transport of leptin in both the Zucker and Koletsky obese rat. Diabetes. 1997;46(3):513-518. doi: 10.2337/diab.46.3.513

 

  1. Michaelis OE IV, Ellwood KC, Tulp OL, Greenwood MR. Effect of feeding sucrose or starch diets on parameters of glucose tolerance in the LA/N-corpulent rat. Nutr Res. 1986;6:95-99. doi: 10.1016/s0271-5317(86)80203-2

 

  1. Raabo E, Terkilden TC. On the enzymatic determination of blood glucose. Scand J Clin and Lab Invest. 1960;12:402-407. doi: 10.3109/00365516009065404

 

  1. Hales CN, Randle PJ. Immunoassay of insulin and insulin antibody precipitate. Biochem J. 1963;88:137-146. doi: 10.1042/bj0880137

 

  1. Wallace TM, Levy JC, Mathews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27(6):1487-1495. doi: 10.2337/diacare.27.6.1487

 

  1. Bentzen CJ, Acuff AJ, Marachal MA, Volk ME. Direct determination of lipoprotein cholesterol distribution with microscale affinity chromatography columns. Clin Chem. 1982;28(7):1451-1456.

 

  1. Bucolo G, David H. Determination of cholesterol lipoproteins via affinity chromatography. Clin Chem. 1973;4:476-481.

 

  1. Freeland RA. Effect of starvation on rat liver enzymes. J Nutr. 1987;91:489-495. doi: 10.1093/jn/91.4.489

 

  1. Lowry OH, Rosebrogh NJ, Farr AL, Randall RJ. Measurement of proteins in tissues. J Biol Chem. 1951;193:265-275.

 

  1. Matschinsky FM, Wilson DF. The Central role of glucokinase in glucose homeostasis: A perspective 50 years after demonstrating the presence of the enzyme in islets of Langerhans. Front Physiol. 2019;10:148. doi: 10.3389/fphys.2019.00148

 

  1. Nie N, Hull CH, Jenkins K, Sternbrunner K, Bent D. Statistical Package for the Social Sciences. 2nd ed. New York: McGraw Hill.

 

  1. Page EB. Ordered hypothesis for multiple treatments: A significance test for linear ranks. J Am Stat Assoc. 1963;58(301):216-230. doi: 10.1080/01621459.1963.10500843

 

  1. Chang GG, Tong L. Structure and function of malic enzymes, a new class of oxidative decarboxylases. Biochemistry. 2003;42:12721-12733. doi: 10.1021/bi035251+

 

  1. Chou BS, Shiau SY. Optimal dietary lipid level for growth of juvenile hybrid tilapia, Oreochromis niloticus X Oreochromis aureus. Aquaculture. 1996;143(2):185-195. doi: 10.1016/0044-8486(96)01266-5

 

  1. Sugimoto S, Nakajima H, Kosaka K, Hosoi H. Review: Miglitol has potential as a therapeutic drug against obesity. Nutr Metab. 2015;12:51. doi: 10.1186/s12986-015-0048-8

 

  1. Boque N, Campion J, Paterman L, et al. Influence of dietary macronutrient composition on adiposity and cellularity of different fat depots in Wistar rats. J Physiol Biochem. 2009;65(4):387-395. doi: 10.1007/BF03185934

 

  1. Scott LJ, Spencer CM. Miglitol: A review of its therapeutic potential in type 2 diabetes mellitus. Drugs. 2000;59(3):521-549. doi: 10.2165/00003495-200059030-00012

 

  1. Coniff RF, Shapiro JA, Robbins D, et al. Reduction of glycosylated hemoglobin and postprandial hyperglycemia by acarbose in patients with NIDDM. A placebo-controlled dose-comparison study. Diabetes Care. 1995;18(6):817-824. doi: 10.2337/diacare.18.6.817

 

  1. Hanefeld M, Fischer S, Schulze J, et al. Therapeutic potentials of acarbose as first-line drug in NIDDM insufficiently treated with diet alone. Diabetes Care. 1991;14(8):732-737. doi: 10.2337/diacare.14.8.732

 

  1. Lee J, Lee S, Zhang H, et al. Interaction of IL-6 and TNF-α contributes to endothelial dysfunction in type 2 diabetic mouse hearts. PLoS One. 2017;12(11):e0187189. doi: 10.1371/journal.pone.0187189

 

  1. Ajuwon KM, Spurlock ME. Palmitate activates the NF-κB transcription factor and induces IL-6 and TNFα expression in 3T3-L1 adipocytes. J Nutr. 2005;135(8):1841-1846. doi: 10.1093/jn/135.8.1841

 

  1. Volpe CM, Abreu LF, Gomes PS, Gonzaga RM, Veloso CA, Nogueira-Machado JA. The Production of nitric oxide, IL-6, and TNF-alpha in palmitate-stimulated PBMNCs is enhanced through hyperglycemia in diabetes. Oxidat Med Cell Longev. 2014;2014(1):479587. doi: 10.1155/2014/479587

 

  1. Nordmann TM, Dror E, Schulze F, et al. The Role of inflamemation in β-cell dedifferentiation. Sci Rep. 2017;7:6285. doi: 10.1038/s41598-017-06731-w

 

  1. King GL. The role of inflammatory cytokines in diabetes and its complications. J Periodontol. 2008;79(8S)1527-1534. doi: 10.1902/jop.2008.080246

 

  1. Martin SS. 3 Myths about cholesterol-lowering statin drugs. In: Home Health Conditions and Diseases, United States: John Hopkins Medicine; 2024.
Share
Back to top
Global Translational Medicine, Electronic ISSN: 2811-0021 Print ISSN: 3060-8600, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept