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Erythritol reduces small intestinal glucose absorption, increases muscle glucose uptake, improves glucose metabolic enzymes activities and increases expression of Glut-4 and IRS-1 in type 2 diabetic rats



Studies have reported that erythritol, a low or non-glycemic sugar alcohol possesses anti-hyperglycemic and anti-diabetic potentials but the underlying mode of actions is not clear. This study investigated the underlying mode of actions behind the anti-hyperglycemic and anti-diabetic potentials of erythritol using different experimental models (experiment 1, 2 and 3).


Experiment 1 examined the effects of increasing concentrations (2.5–20%) of erythritol on glucose absorption and uptake in isolated rat jejunum and psoas muscle, respectively. Experiments 2 and 3 examined the effects of a single oral dose of erythritol (1 g/kg bw) on intestinal glucose absorption, gastric emptying and postprandial blood glucose increase, glucose tolerance, serum insulin level, muscle/liver hexokinase and liver glucose-6 phosphatase activities, liver and muscle glycogen contents and mRNA and protein expression of muscle Glut-4 and IRS-1 in normal and type 2 diabetic animals.


Experiment 1 revealed that erythritol dose dependently enhanced muscle glucose ex vivo. Experiment 2 demonstrated that erythritol feeding delayed gastric emptying and reduced small intestinal glucose absorption as well as postprandial blood glucose rise, especially in diabetic animals. Experiment 3 showed that erythritol feeding improved glucose tolerance, muscle/liver hexokinase and liver glucose-6 phosphatase activities, glycogen storage and also modulated expression of muscle Glut-4 and IRS-1 in diabetic animals.


Data suggest that erythritol may exert anti-hyperglycemic effects not only via reducing small intestinal glucose absorption, but also by increasing muscle glucose uptake, improving glucose metabolic enzymes activity and modulating muscle Glut-4 and IRS-1 mRNA and protein expression. Hence, erythritol may be a useful dietary supplement for managing hyperglycemia, particularly for T2D.

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Quantification cycle


Diabetic control


qPCR efficiency


Glucose absorption index


Gastrointestinal tract


Glucose transporter type 4


Homeostatic model assessment—insulin resistance


Insulin receptor substrate-1


Normal control


Oral glucose tolerance test


Inorganic phosphate


Real-time PCR


Type 2 diabetes


  1. 1.

    Pratley RE (2013) The early treatment of type 2 diabetes. Am J Med 126:S2–S9

    Article  Google Scholar 

  2. 2.

    International Diabetes Federation (2015) IDF Diabetes Atlas, 7th edn

  3. 3.

    Bahrami J, Gerstein H (2016) The prevalence of undiagnosed type 2 diabetes on the General Medicine Ward. Can J Diabetes 40:S49–S50

    Article  Google Scholar 

  4. 4.

    Pratley R, Weyer C (2001) The role of impaired early insulin secretion in the pathogenesis of type II diabetes mellitus. Diabetologia 44:929–945

    CAS  Article  Google Scholar 

  5. 5.

    Kahn SE (2003) The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 43:3–19

    Article  Google Scholar 

  6. 6.

    Thorburn AW, Storlien LH, Jenkins AB, Khouri S, Kraegen EW (1989) Fructose-induced in vivo insulin resistance and elevated plasma triglyceride levels in rats. Am J Clin Nutr 49:1155–1163

    CAS  Article  Google Scholar 

  7. 7.

    Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ (2002) Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr 76:911–922

    CAS  Article  Google Scholar 

  8. 8.

    Astrup A, Raben A, Vasilaras TH, Moller AC (2002) Sucrose in soft drinks is fattening: a randomized 10 week study in overweight subjects. Am J Clin Nutr 7:405

    Google Scholar 

  9. 9.

    Hu FB (2003) Sedentary lifestyle and risk of obesity and type 2 diabetes. Lipids 38:103–108

    CAS  Article  Google Scholar 

  10. 10.

    Amod A, Ascott-Evans BH, Berg GI et al (2012) The 2012 Society for Endocrinology, Metabolism and Diabetes of South Africa guideline for the management of type 2 diabetes. JEMDSA 17:1–95

    Google Scholar 

  11. 11.

    Livesey G (2003) Health potential of polyols as sugar replacers, with emphasis on low glycaemic properties. Nutr Res Rev 16:163–191

    CAS  Article  Google Scholar 

  12. 12.

    Fitch C, Keim KS (2012) Position of the Academy of Nutrition and Dietetics: use of nutritive and non nutritive sweeteners. J Acad Nutr Diet 112:739–758

    Article  Google Scholar 

  13. 13.

    O’Donnell K, Kearsley MW (2012) Sweeteners and sugar alternatives in food technology, 2nd edn. Wiley, UK

    Book  Google Scholar 

  14. 14.

    Bornet FRJ, Blayo A, Dauchy F, Slama G (1996) Plasma and urine kinetics of erythritol after oral ingestion by healthy humans. Regul Toxicol Pharmaco 24:S280–S286

    CAS  Article  Google Scholar 

  15. 15.

    Yokozawa T, Kim HY, Cho EJ (2002) Erythritol attenuates the diabetic oxidative stress through modulating glucose metabolism and lipid peroxidation in streptozotocin-induced diabetic rats. J Agric Food Chem 50:5485–5489

    CAS  Article  Google Scholar 

  16. 16.

    Ishikawa M, Miyashita M, Kawashima Y et al (1996) Effects of oral administration of erythritol on patients with diabetes. Regul Toxicol Pharmacol 24:S303–S308

    CAS  Article  Google Scholar 

  17. 17.

    Flint N, Hamburg NM, Holbrook M et al (2014) Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: a pilot study. Acta Diabetol 51:513–516

    CAS  PubMed  Google Scholar 

  18. 18.

    Woelnerhanssen BK, Cajacob L, Keller N et al (2016) Gut hormone secretion, gastric emptying and glycemic responses to erythritol and xylitol in lean and obese subjects. Am J Physiol Endocrinol Metab 310:E1053–E1061

    Article  Google Scholar 

  19. 19.

    Chukwuma CI, Ibrahim MA, Islam MS (2016) Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study. J Physiol Biochem 72:791–801

    CAS  Article  Google Scholar 

  20. 20.

    Chukwuma CI, Islam MS (2017) Sorbitol increases muscle glucose uptake ex vivo and inhibits intestinal glucose absorption ex vivo and in normal and type 2 diabetic rats. Appl Physiol Nutr Metab 42:377–383

    CAS  Article  Google Scholar 

  21. 21.

    Wilson RD, Islam MS (2012) Fructose-fed streptozotocin injected rat: an alternative model for type 2 diabetes. Pharmacol Rep 64:129–139

    CAS  Article  Google Scholar 

  22. 22.

    Storey D, Lee A, Bornet F, Brouns F (2007) Gastrointestinal tolerance of erythritol and xylitol ingested in a liquid. Eur J Clin Nutr 61:349–354

    CAS  Article  Google Scholar 

  23. 23.

    Ngubane PS, Masola B, Musabayane CT (2011) The effects of Syzygium aromaticum derived oleanolic acid on glycogenic enzymes in streptozotocin induced-diabetic rats. Ren Fail 33:434–439

    CAS  Article  Google Scholar 

  24. 24.

    Lo S, Russel JC, Taylor AW (1970) Determination of glycogen in small tissue samples. J Appl Physiol 28:234–236

    CAS  Article  Google Scholar 

  25. 25.

    Sigma Aldrich (2016) Enzymatic assay of hexokinase. Accessed 28 June 2016

  26. 26.

    Sigma Aldrich (2016) Enzymatic activity of glucose-6-phosphatase [EC]. Accessed 2 July 2016

  27. 27.

    Rio DC, Ares M Jr., Hannon GJ, Nilsen TW (2010) Purification of RNA using TRIzol (TRI reagent). Cold Spring Harb Protoc. doi:10.1101/pdb.prot5439

    Article  PubMed  Google Scholar 

  28. 28.

    Araujo EP, Amaral ME, Filiputti E et al (2004) Restoration of insulin secretion in pancreatic islets of protein-deficient rats by reduced expression of insulin receptor substrate (IRS)-1 and IRS-2. J Endocrinol 181:25–38

    CAS  Article  Google Scholar 

  29. 29.

    Im SS, Kwon SK, Kang SY et al (2006) Regulation of GLUT4 gene expression by SREBP-1c in adipocytes. Biochem J 399:131–139

    CAS  Article  Google Scholar 

  30. 30.

    Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:2002–2007

    Article  Google Scholar 

  31. 31.

    Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3:1101–1108

    CAS  Article  Google Scholar 

  32. 32.

    Rider AK, Schedl HP, Nokes G, Shining S (1967) Small intestinal glucose transport. Proximal-distal kinetic gradients. J Gen Physiol 50:1173–1182

    CAS  Article  Google Scholar 

  33. 33.

    Riesenfeld G, Sklan D, Bar A, Eisner U, Hurwitz S (1980) Glucose absorption and starch digestion in the intestine of the chicken. J Nutr 110:117–121

    CAS  Article  Google Scholar 

  34. 34.

    Salminen E, Salminen S, Porkka L, Koivistoinen P (1984) The effects of xylitol on gastric emptying and secretion of gastric inhibitory polypeptide in the rat. J Nutr 114:2201–2203

    CAS  Article  Google Scholar 

  35. 35.

    Aronoff SL, Berkowitz K, Shreiner B, Want L (2004) Glucose metabolism and regulation: beyond insulin and glucagon. Diabetes Spectr 17:183–190

    Article  Google Scholar 

  36. 36.

    Horowitz M, Wishart JM, Jones KL, Hebbard GS (1996) Gastric emptying in diabetes: an overview. Diabet Med 13:S16–S22

    CAS  PubMed  Google Scholar 

  37. 37.

    Phillips WT, Schwartz JG, McMahan CA (1991) Rapid gastric emptying in patients with early non-insulin-dependent diabetes mellitus. N Engl J Med 324:130–131

    CAS  Article  Google Scholar 

  38. 38.

    Ranganath L, Norris F, Morgan L, Wright J, Marks V (1998) Delayed gastric emptying occurs following acarbose administration and is a further mechanism for its anti-hyperglycaemic effect. Diabet Med 15:120–124

    CAS  Article  Google Scholar 

  39. 39.

    Chukwuma CI, Islam MS (2015) Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study. Food Funct 6:955–962

    CAS  Article  Google Scholar 

  40. 40.

    Chang L, Chiang S, Saltiel AR (2004) Insulin signaling and the regulation of glucose transport. Mol Med 10:65–71

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    González-Sánchez JL, Serrano-Ríos M (2007) Molecular basis of insulin action. Drug News Perspect 20:527–531

    Article  Google Scholar 

  42. 42.

    Wu C, Khan SA, Lange AJ (2005) Regulation of glycolysis-role of insulin. Exp Gerontol 40:894–899

    CAS  Article  Google Scholar 

  43. 43.

    Fröjdö S, Vidal H, Pirola L (2009) Alterations of insulin signaling in type 2 diabetes: a review of the current evidence from humans. Biochim Biophys Acta 1792:83–92

    Article  Google Scholar 

  44. 44.

    Boucher J, Kleinridders A, Kahn CR (2014) Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol. doi:10.1101/cshperspect.a009191

    Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Carvalho E, Jansson PA, Nagaev I, Wenthzel AM, Smith U (2001) Insulin resistance with low cellular IRS-1 expression is also associated with low GLUT4 expression and impaired insulin-stimulated glucose transport. FASEB J 15:1101–1103

    CAS  PubMed  Google Scholar 

  46. 46.

    Wang Y, Nishina PM, Naggert JK (2009) Degradation of IRS1 leads to impaired glucose uptake in adipose tissue of the type 2 diabetes mouse model TALLYHO/Jng. J Endocrinol 203:65–74

    CAS  Article  Google Scholar 

  47. 47.

    Gual P, Le Marchand-Brustel Y, Tanti J (2003) Positive and negative regulation of glucose uptake by hyperosmotic stress. Diabetes Metab 29:566–575

    CAS  Article  Google Scholar 

  48. 48.

    Zorzano A, Camps M (1997) Glut 4 in insulin resistance. In: Gould GW (ed) Facilitative glucose transporters. R.G. Landes Company and Chapman & Hall, US and Canada, pp 137–166. = 4fpHl_KgxHIC&pg = PA149&lpg = PA149&dq = Postranslational + modification + of + Glut + 4&source = bl&ots = Dvs0Z6HTPs&sig = 35_nRLMKXpVUDGyEK00RU2UVbqM&hl = en&sa = X&ved = 0ahUKEwi79NnynvLUAhXKLMAKHfePDsYQ6AEIRjAG#v = onepage&q = Postranslational%20modification%20of%20Glut%204&f = false. Accessed 2 July 2017

  49. 49.

    Liu Z, Barrett EJ, Dalkin AC, Zwart AD, Chou JY (1994) Effect of acute diabetes on rat hepatic glucose-6-phosphatase activity and its messenger RNA level. Biochem Biophys Res Commun 205:680–686

    CAS  Article  Google Scholar 

  50. 50.

    Lenzen S (2014) A fresh view of glycolysis and glucokinase regulation: history and current status. J Biol Chem 289:12189–12194

    CAS  Article  Google Scholar 

  51. 51.

    Clore JN, Stillman J, Sugerman H (2000) Glucose-6-phosphatase flux in vitro is increased in type 2 diabetes. Diabetes 49:969–974

    CAS  Article  Google Scholar 

  52. 52.

    Kruszynska YT, Home PD (1988) Liver and muscle insulin sensitivity, glycogen concentration and glycogen synthase activity in a rat model of non-insulin-dependent diabetes. Diabetologia 31:304–309

    CAS  Article  Google Scholar 

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This study was supported by Competitive Research Grant from the University of KwaZulu-Natal, Durban and Grant Support for Women and Young researchers from the National Research Foundation (NRF), Pretoria, South Africa. Special thanks to Dr. M. Singh, Dr. Linda Bester, David Mompe, Olajumoke Daramola, Nathasha Pillay, Collins Odjedjare, Dinesh Jagganath, Dr. M. Ngcobo, Lethukuthula Ngobese and Deliwe Mdakane for their assistance during this study.

Author information




CCI carried out the experimental section of the study and drafted the manuscript, MR assisted in carrying out the gene expression and CAA and NS conducted the Western blot analysis of the study, while IMS supervised the study and edited the manuscript before submission.

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Correspondence to Md. Shahidul Islam.

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Chukwuma, C.I., Mopuri, R., Nagiah, S. et al. Erythritol reduces small intestinal glucose absorption, increases muscle glucose uptake, improves glucose metabolic enzymes activities and increases expression of Glut-4 and IRS-1 in type 2 diabetic rats. Eur J Nutr 57, 2431–2444 (2018).

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  • Erythritol
  • Glucose absorption
  • Glucose uptake
  • Type 2 diabetes (T2D)
  • Glut-4
  • IRS-1