High-fructose diet preserves beta-cell mass and prevents diabetes in nonobese diabetic mice: A potential role for increased insulin receptor substrate-2 expression.
We demonstrate that a high-fructose diet reduces the incidence of diabetes in nonobese diabetic (NOD) mice (31.2% v 57.1% on regular chow (RC); P =.009). In a second cohort of mice, we evaluated potential mechanisms for the protective effect of the high-fructose (HF) diet and whether the metabolic changes are strain-specific. Sixty NOD and 60 Balb/c mice were randomized at weaning into HF- and RC-fed groups (30 mice each) and followed for 28 weeks. Glucose tolerance testing demonstrated improved glucose tolerance in HF diet groups (P =.001 in Balb/c; P =.04 in NOD mice at 6 months). beta-cell mass was preserved in NOD mice on the HF diet, but remained unchanged in Balb/c mice. In NOD mice, hepatic insulin receptor substrate (IRS)-2 protein expression increased by 2-fold (P =.01 for 2 v 6 months) in HF-fed mice and was 53% +/- 15% higher (P =.01) in the HF diet versus RC groups at 6 months of age. IRS-2 expression was also increased in skeletal muscle of NOD mice and in both liver and muscle of Balb/c mice. Our data suggest that a HF diet improves glucose tolerance in both NOD and Balb/c mice. The improved glucose tolerance may be related to increased IRS-2 expression and, in NOD mice, preservation of beta-cell mass.
Orban
T
T
Section on Immunology, Joslin Diabetes Center, Boston, MA 02115, USA.
Landaker
E
E
Ruan
Z
Z
Cordeman
T P
TP
Weitgasser
R
R
Bonner-Weir
S
S
Jackson
R A
RA
Patti
M E
ME
D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000178:diet therapy / Q000503:physiopathology / Q000517:prevention & control*; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D005260:Female; D005526:Food, Formulated; D005632:Fructose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D015994:Incidence; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526298:Irs2 protein, mouse; D010750:Phosphoproteins; D014280:Triglycerides; D005632:Fructose