title: Effect of Hypertriglyceridemia on Beta Cell Mass and Function in ApoC3 Transgenic Mice.
abstract: Hypertriglyceridemia results from increased production and decreased clearance of triglyceride-rich very low-density lipoproteins, a pathological condition that accounts for heightened risk of ischemic vascular diseases in obesity and type 2 diabetes. Despite its intimate association with insulin resistance, whether hypertriglyceridemia constitutes an independent risk for beta cell dysfunction in diabetes is unknown. Answering this fundamental question is stymied by the fact that hypertriglyceridemia is intertwined with hyperglycemia and insulin resistance in obese and diabetic subjects. To circumvent this limitation, we took advantage of apolipoprotein C3 (ApoC3)-transgenic mice, a model with genetic predisposition to hypertriglyceridemia. We showed that ApoC3-transgenic mice, as opposed to age/sex-matched wild-type littermates, develop hypertriglyceridemia with concomitant elevations in plasma cholesterol and non-esterified fatty acid levels. Anti-insulin and anti-glucagon dual immunohistochemistry in combination with morphometric analysis revealed that ApoC3-transgenic and wild-type littermates had similar beta cell and alpha cell masses as well as islet size and architecture. These effects correlated with similar amplitudes of glucose-stimulated insulin secretion and similar degrees of postprandial glucose excursion in ApoC3-transgenic versus wild-type littermates. Oil Red O histology did not visualize lipid infiltration into islets, correlating with the lack of ectopic triglyceride and cholesterol depositions in the pancreata of ApoC3-transgenic versus wild-type littermates. ApoC3-transgenic mice, despite persistent hypertriglyceridemia, maintained euglycemia under both fed and fasting conditions without manifestation of insulin resistance and fasting hyperinsulinemia. Thus, hypertriglyceridemia per se is not an independent risk factor for beta cell dysfunction in ApoC3 transgenic mice.
authors.affiliation: From the Department of Pediatrics, Division of Pediatric Endocrinology, and the Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, China, and.
authors.forename: Yun-Zi
authors.initials: YZ
authors.lastname: Liu
authors.affiliation: From the Department of Pediatrics, Division of Pediatric Endocrinology, and the Department of Endocrinology and Metabolism, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Cheng
authors.affiliation: From the Department of Pediatrics, Division of Pediatric Endocrinology, and.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: From the Department of Pediatrics, Division of Pediatric Endocrinology, and.
authors.forename: Sojin
authors.initials: S
authors.lastname: Lee
authors.affiliation: From the Department of Pediatrics, Division of Pediatric Endocrinology, and.
authors.forename: Jun
authors.initials: J
authors.lastname: Yamauchi
authors.affiliation: the Department of Surgery, Division of Pediatric Surgery, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Xiao
authors.affiliation: the Department of Surgery, Division of Pediatric Surgery, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.
authors.forename: George
authors.initials: G
authors.lastname: Gittes
authors.affiliation: the Department of Endocrinology and Metabolism, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Qu
authors.affiliation: the Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, China, and.
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Jiang
authors.affiliation: From the Department of Pediatrics, Division of Pediatric Endocrinology, and dongh@pitt.edu.
authors.forename: H Henry
authors.initials: HH
authors.lastname: Dong
mesh_terms: D000818:Animals; D053305:Apolipoprotein C-III / Q000235:genetics / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity
chemical_list: D053305:Apolipoprotein C-III; D001786:Blood Glucose; D005947:Glucose
keywords: ApoC3; apolipoprotein c; beta cell (β cell); dyslipidemia; lipid metabolism; obesity; type 2 diabetes