Long-term High-fat High-sucrose Diet Promotes Enlarged Islets and β-Cell Damage by Oxidative Stress in Bama Minipigs.

Abstract

The effect of a long-term high-fat, high-caloric diet on the dysfunction of pancreas has not been clarified. We investigated the pancreatic histopathology and β-cell apoptosis in Bama minipigs after 23 months on a high-fat high-sucrose diet (HFHSD). Bama minipigs were randomly assigned to control (n = 6) and HFHSD groups (n = 6) for 23 months, and biochemical parameters were measured. Pancreata were subjected to histological analysis, followed by assessment with transmission electron microscopy. Lipid peroxidation was determined by the malondialdehyde concentration and antioxidant enzyme activity. Β-cell apoptosis was measured by an immunohistochemical method. In the HFHSD group, the islets were enlarged, and the pancreatic tissue had observed significant fatty infiltration. Moreover, the feeding program damaged the normal pancreatic tissue structure. The level of lipid peroxidation was increased, and the activities of pancreatic antioxidant enzymes were significantly decreased. The expression levels of caspase-3, Bax, and insulin were significantly increased (P < 0.05), and the expression levels of proliferating cell nuclear antigen and Bcl-2 were decreased (P < 0.05). The long-term HFHSD promotes pancreatic steatosis and oxidative stress, which increases β-cell apoptosis as indicated by the activation of caspase-3 through the mitochondrial pathway (Bcl-2/Bax).