title: Gluten-free diet increases beta-cell volume and improves glucose tolerance in an animal model of type 2 diabetes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: The Bartholin Institute, Rigshospitalet, Copenhagen, Denmark. martinhj9@gmail.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Haupt-Jorgensen
authors.affiliation: The Bartholin Institute, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Buschard
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Axel K
authors.initials: AK
authors.lastname: Hansen
authors.affiliation: The Bartholin Institute, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Knud
authors.initials: K
authors.lastname: Josefsen
authors.affiliation: The Bartholin Institute, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Julie Christine
authors.initials: JC
authors.lastname: Antvorskov
mesh_terms: D000818:Animals; D048429:Cell Size; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy* / Q000378:metabolism; D055050:Diet, Gluten-Free; D004195:Disease Models, Animal; D018149:Glucose Intolerance / Q000517:prevention & control*; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
keywords: beta-cell volume; glucose tolerance; gluten-free diet; pancreas volume; type 2 diabetes