Severe Insulin Resistance and Moderate Glomerulosclerosis in a Minipig Model Induced by High-Fat/ High-Sucrose/ High-Cholesterol Diet

  • LIU Yi
    Institute of Cardiovascular Research, School of Life Sciences and Technology, Nanhua University Medical College of Shaoguan University
  • WANG Zongbao
    Department of Laboratory Animal Science, Nanhua University
  • YIN Weidong
    Institute of Cardiovascular Research, School of Life Sciences and Technology, Nanhua University
  • LI Qinkai
    Institute of Cardiovascular Research, School of Life Sciences and Technology, Nanhua University
  • CAI Manbo
    Institute of Cardiovascular Research, School of Life Sciences and Technology, Nanhua University
  • ZHANG Chi
    Institute of Cardiovascular Research, School of Life Sciences and Technology, Nanhua University
  • XIAO Junxia
    Institute of Cardiovascular Research, School of Life Sciences and Technology, Nanhua University
  • HOU Hongjie
    Institute of Cardiovascular Research, School of Life Sciences and Technology, Nanhua University
  • LI Hongguang
    Institute of Cardiovascular Research, School of Life Sciences and Technology, Nanhua University
  • ZU Xiuhong
    Institute of Cardiovascular Research, School of Life Sciences and Technology, Nanhua University

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Abstract

To develop a minipig model of type 2 diabetes that simulates the common manifestations of the metabolic abnormalities and resembles the kidney pathology of type 2 diabetes in the human population, male Chinese Bama minipigs were divided into 2 groups (5 in each) and fed with a control diet (CD) or high-fat/ high-sucrose/ high-cholesterol diet (HFSCD) for 5 months. The biochemical parameters of blood and urine, and the oral glucose tolerance test were monitored after the feeding program. The insulin resistance was estimated by the HOMA-IR index and the glucose elimination constant (KG), and beta-cell function by the HOMA-beta index and the acute insulin response (AIR). Glomerulosclerosis index (GSI) was semi-quantitated by the degree of glomerular lesions in kidney sections stained with Masson trichrome. Extracellular matrix deposition in the kidney was examined by the protein expression of type IV collagen, connective tissue growth factor (CTGF) and matrix metalloproteinases 2 (MMP-2) using immunohistochemistry. Feeding HFSCD to minipigs markedly caused hyperglycaemia, hyperinsulinaemia and dyslipidaemia. HOMA-IR was significantly increased while HOMA-beta, AIR and KG were obviously decreased in the HFSCD group compared with control group. Microalbuminuria, glucosuria and moderate glomerulosclerosis were exhibited in HFSCD-fed minipigs. The expression of type IV collagen and CTGF was elevated whereas that of MMP-2 was reduced in the kidneys of HFSCD group compared with the CD group. We concluded that feeding HFSCD to Chinese Bama minipigs for 5 months can induce humanoid type 2 diabetes and early-stage diabetic nephropathy, and accelerate extracellular matrix deposition and glomerulosclerosis.<br>

Journal

  • Experimental Animals

    Experimental Animals 56 (1), 11-20, 2007

    Japanese Association for Laboratory Animal Science

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