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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

Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusion

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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Abbreviations

Cq:

Quantification cycle

DBC:

Diabetic control

E:

qPCR efficiency

GAI:

Glucose absorption index

GIT:

Gastrointestinal tract

Glut-4:

Glucose transporter type 4

HOMA-IR:

Homeostatic model assessment—insulin resistance

IRS-1:

Insulin receptor substrate-1

NC:

Normal control

OGTT:

Oral glucose tolerance test

Pi:

Inorganic phosphate

qPCR:

Real-time PCR

T2D:

Type 2 diabetes

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Acknowledgements

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.

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Authors

Contributions

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.

Corresponding author

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). https://doi.org/10.1007/s00394-017-1516-x

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Keywords

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