Dietary fructose accelerates the development of diabetes in UCD-T2DM rats: amelioration by the antioxidant, alpha-lipoic acid.
Sustained fructose consumption has been shown to induce insulin resistance and glucose intolerance, in part, by promoting oxidative stress. Alpha-lipoic acid (LA) is an antioxidant with insulin-sensitizing activity. The effect of sustained fructose consumption (20% of energy) on the development of T2DM and the effects of daily LA supplementation in fructose-fed University of California, Davis-Type 2 diabetes mellitus (UCD-T2DM) rats, a model of polygenic obese T2DM, was investigated. At 2 mo of age, animals were divided into three groups: control, fructose, and fructose + LA (80 mg LA.kg body wt(-1).day(-1)). One subset was followed until diabetes onset, while another subset was euthanized at 4 mo of age for tissue collection. Monthly fasted blood samples were collected, and an intravenous glucose tolerance test (IVGTT) was performed. Fructose feeding accelerated diabetes onset by 2.6 +/- 0.5 mo compared with control (P < 0.01), without affecting body weight. LA supplementation delayed diabetes onset in fructose-fed animals by 1.0 +/- 0.7 mo (P < 0.05). Fructose consumption lowered the GSH/GSSG ratio, while LA attenuated the fructose-induced decrease of oxidative capacity. Insulin sensitivity, as assessed by IVGTT, decreased in both fructose-fed and fructose + LA-supplemented rats. However, glucose excursions in fructose-fed LA-supplemented animals were normalized to those of control via increased glucose-stimulated insulin secretion. Fasting plasma triglycerides were twofold higher in fructose-fed compared with control animals at 4 mo, and triglyceride exposure during IVGTT was increased in both the fructose and fructose + LA groups compared with control. In conclusion, dietary fructose accelerates the onset of T2DM in UCD-T2DM rats, and LA ameliorates the effects of fructose by improving glucose homeostasis, possibly by preserving beta-cell function.
Cummings
Bethany P
BP
Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, One Shields Ave., Davis, CA 95616, USA.
Stanhope
Kimber L
KL
Graham
James L
JL
Evans
Joseph L
JL
Baskin
Denis G
DG
Griffen
Steven C
SC
Havel
Peter J
PJ
D052242:Adiponectin / Q000097:blood; D000821:Animal Feed; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D004041:Dietary Fats / Q000494:pharmacology; D050171:Dyslipidemias / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005632:Fructose / Q000494:pharmacology*; D018149:Glucose Intolerance / Q000188:drug therapy / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D053208:Kaplan-Meier Estimate; D020738:Leptin / Q000097:blood; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D008063:Thioctic Acid / Q000494:pharmacology*; D024505:Tocopherols / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D018799:Intercellular Adhesion Molecule-1; D005632:Fructose; D008063:Thioctic Acid; D024505:Tocopherols