Gluten-free diet increases beta-cell volume and improves glucose tolerance in an animal model of type 2 diabetes

Diabetes Metab Res Rev. 2016 Oct;32(7):675-684. doi: 10.1002/dmrr.2802. Epub 2016 Apr 21.


Background: Gluten-free (GF) diet alleviates type 1 diabetes in animal models and possibly in humans. We recently showed that fatty acid-induced insulin secretion is enhanced by enzymatically digested gluten (gliadin) stimulation in INS-1E insulinoma cells. We therefore hypothesized that GF diet would induce beta-cell rest and ameliorate type 2 diabetes.

Methods: C57BL/6JBomTac (B6) mice were fed a high-fat (HF), gluten-free high-fat (GF-HF), standard (STD) or gluten-free (GF) diet for 42 weeks.

Results: Short-term (6-24 weeks) GF-HF versus HF feeding impaired glucose tolerance and increased fasting glucose. Long-term (36-42 weeks) GF-HF versus HF feeding improved glucose tolerance and decreased fasting leptin. Mice fed a GF-HF versus HF diet for 42 weeks showed higher volumes of beta cells, islets and pancreas. The beta-cell volume correlated with the islet- and pancreas volume as well as body weight. GF-HF versus HF diet did not influence toll-like receptor 4 (Tlr4), interleukin 1 (IL-1), interleukin 6 (IL-6) or tumour necrosis factor-alpha (TNF-alpha) mRNA expression in intestine. STD versus GF feeding did not affect any parameter studied.

Conclusions: Long-term feeding with GF-HF versus HF increases beta-cell volume and improves glucose tolerance in B6 mice. The mechanism may include beta-cell rest, but is unlikely to include TLR4 and proinflammatory cytokines in the intestine. Beta-cell volume correlates with pancreas volume and body weight, indicating that insulin secretion capacity controls pancreas volume. Thus, long-term GF diets may be beneficial for obese type 2 diabetes patients and trials should be performed. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: beta-cell volume; glucose tolerance; gluten-free diet; pancreas volume; type 2 diabetes.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cell Size
  • Diabetes Mellitus, Type 2 / diet therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diet, Gluten-Free*
  • Disease Models, Animal*
  • Glucose Intolerance / prevention & control*
  • Glucose Tolerance Test
  • Insulin Resistance
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL