Abstract AP-1
SERUM ANGIOPOIETIN-LIKE PROTEIN 6, RISK OF TYPE 2 DIABETES, AND RESPONSE TO HYPERGLYCEMIA: A PROSPECTIVE COHORT STUDY 1,2
KANG-CHIH FAN, 3HUNG-TSUNG WU, 4JUNG-NAN WEI, 5LEE-MING CHUANG, 1 CHIH-YAO HSU, 1I-WENG YEN, 1CHIA-HUNG LIN, 5MAO-SHIN LIN, 5 SHYANG-RONG SHIH, 6SHU-HUEI WANG, 5TIEN-JYUN CHANG, AND 5HUNG-YUAN LI 1
Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan; 2Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan; 4Chia Nan University of Pharmacy and Science, Tainan, Taiwan; 5Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 6Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
Purpose Angiopoietin-like protein 6 (ANGPTL6) is a hepatokine that improves insulin sensitivity in animals. However, serum ANGPTL6 concentration was found to be higher in human participants with diabetes or metabolic syndrome in cross-sectional studies, implying that ANGPTL6 may be induced to counteract hyperglycemia. To investigate whether serum ANGPTL6 can predict incident diabetes and explore whether glucose or insulin can regulate ANGPTL6 expression and secretion. Method This cohort study included adults without diabetes at baseline who were followed every 2 years for incident diabetes. Serum ANGPTL6 concentrations were measured at baseline and during oral glucose tolerance tests (OGTTs). A hepatic cell line, HepG2, and diet-induced obesity mouse model were used to evaluate the response of ANGPTL6 expression and secretion to hyperglycemia and the metabolic syndrome. Result We recruited 1103 participants without diabetes at baseline. During the 4.22-year followup, 113 (10.2%) participants developed incident diabetes. Serum ANGPTL6 was negatively associated with the incidence of diabetes (adjusted hazard ratio, 0.77; P = 0.042). However, serum ANGPTL6 level was higher in participants with prediabetes (P = 0.018) and was elevated during OGTT. In HepG2 cells, treatment with glucose, but not insulin, induced ANGPTL6 expression. Hepatic ANGPTL6 expression and serum ANGPTL6 concentrations were significantly higher in mice fed with a high-fat diet than in those fed with a standard chow (both P < 0.05). Conclusion A high serum ANGPTL6 level is associated with a low incidence of diabetes in humans. ANGPTL6 is expressed and secreted in response to hyperglycemia to maintain glucose homeostasis.
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