TY - JOUR

T1 - Gluten-free diet increases beta-cell volume and improves glucose tolerance in an animal model of type 2 diabetes

AU - Haupt-Jørgensen, Martin

AU - Buschard, Karsten

AU - Hansen, Axel Kornerup

AU - Josefsen, Knud

AU - Antvorskov, Julie Christine

PY - 2016/10

Y1 - 2016/10

N2 - BackgroundGluten-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.MethodsC57BL/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.ResultsShort-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.ConclusionsLong-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.

AB - BackgroundGluten-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.MethodsC57BL/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.ResultsShort-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.ConclusionsLong-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.

KW - type 2 diabetes

KW - gluten-free diet

KW - beta-cell volume

KW - pancreas volume

KW - glucose tolerance

U2 - 10.1002/dmrr.2802

DO - 10.1002/dmrr.2802

M3 - Journal article

C2 - 26991675

VL - 32

SP - 675

EP - 684

JO - Diabetes/Metabolism Research and Reviews

JF - Diabetes/Metabolism Research and Reviews

SN - 1520-7552

IS - 7

ER -