title: Glucose Uptake and Triacylglycerol Synthesis Are Increased in Barth Syndrome Lymphoblasts.
abstract: Barth syndrome (BTHS) is an X-linked genetic disease resulting in loss of cardiolipin (Ptd2Gro). Patients may be predisposed to hypoglycemia and exhibit increases in whole-body glucose disposal rates and a higher fat mass percentage. We examined the reasons for this in BTHS lymphoblasts. BTHS lymphoblasts exhibited a 60% increase (p < 0.004) in 2-[1,2-3H(N)]deoxy-D-glucose uptake, a 40% increase (p < 0.01) in glucose transporter-3 protein expression, an increase in phosphorylated-adenosine monophosphate kinase (AMPK) and a 58% increase (p < 0.001) in the phosphorylated-AMPK/AMPK ratio compared to controls. In addition, BTHS lymphoblasts exhibited a 90% (p < 0.001) increase in D-[U-14C]glucose incorporated into 1,2,3-triacyl-sn-glycerol (TAG) and a 29% increase (p < 0.025) in 1,2-diacyl-sn-glycerol acyltransferase-2 activity compared to controls. Thus, BTHS lymphoblasts exhibit increased glucose transport and increased glucose utilization for TAG synthesis. These results may, in part, explain why BTHS patients exhibit an increase in whole-body glucose disposal rates, may be predisposed to hypoglycemia and exhibit a higher fat mass percentage.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Health Sciences, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB, R3E 0W3, Canada.
authors.forename: Edgard M
authors.initials: EM
authors.lastname: Mejia
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Health Sciences, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB, R3E 0W3, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Zinko
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Health Sciences, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB, R3E 0W3, Canada.|Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Kristin D
authors.initials: KD
authors.lastname: Hauff
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Health Sciences, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB, R3E 0W3, Canada.
authors.forename: Fred Y
authors.initials: FY
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pathophysiology, DREAM Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, R3E 0T6, Canada.
authors.forename: Amir
authors.initials: A
authors.lastname: Ravandi
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Health Sciences, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB, R3E 0W3, Canada. ghatch@chrim.ca.|Biochemistry and Medical Genetics, Center for Research and Treatment of Atherosclerosis, DREAM Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, R3E 0T6, Canada. ghatch@chrim.ca.
authors.forename: Grant M
authors.initials: GM
authors.lastname: Hatch
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D056889:Barth Syndrome / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005947:Glucose / Q000378:metabolism*; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D051274:Glucose Transporter Type 3; C495687:SLC2A3 protein, human; D014280:Triglycerides; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: Barth syndrome; Cardiolipin; Glucose transport; Metabolism; Triacylglycerol synthesis