Dietary fructose accelerates the development of diabetes in UCD-T2DM rats: Amelioration by the antioxidant, α-lipoic acid

Bethany P. Cummings, Kimber Stanhope, James L. Graham, Joseph L. Evans, Denis G. Baskin, Steven C. Griffen, Peter J Havel

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

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 (UCDT2DM) 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 fructosefed animals by 1.0 ± 0.7 mo (P < 0.05). Fructose consumption lowered the GSH/GSSG ratio, while LA attenuated the fructoseinduced 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 β-cell function.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume298
Issue number5
DOIs
StatePublished - May 2010

Keywords

  • Dyslipidemia
  • Glucose tolerance
  • Islet function
  • Oxidative capacity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Dietary fructose accelerates the development of diabetes in UCD-T2DM rats: Amelioration by the antioxidant, α-lipoic acid'. Together they form a unique fingerprint.

  • Cite this