title: Pigment epithelium-derived factor (PEDF) regulates metabolism and insulin secretion from a clonal rat pancreatic beta cell line BRIN-BD11 and mouse islets.
abstract: Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein, associated with lipid catabolism and insulin resistance. In the present study, PEDF increased chronic and acute insulin secretion in a clonal rat β-cell line BRIN-BD11, without alteration of glucose consumption. PEDF also stimulated insulin secretion from primary mouse islets. Seahorse flux analysis demonstrated that PEDF did not change mitochondrial respiration and glycolytic function. The cytosolic presence of the putative PEDF receptor - adipose triglyceride lipase (ATGL) - was identified, and ATGL associated stimulation of glycerol release was robustly enhanced by PEDF, while intracellular ATP levels increased. Addition of palmitate or ex vivo stimulation with inflammatory mediators induced β-cell dysfunction, effects not altered by the addition of PEDF. In conclusion, PEDF increased insulin secretion in BRIN-BD11 and islet cells, but had no impact on glucose metabolism. Thus elevated lipolysis and enhanced fatty acid availability may impact insulin secretion following PEDF receptor (ATGL) stimulation.
authors: School of Biomedical Sciences, CHIRI Biosciences, Curtin University, GPO Box U1987, Perth, Western Australia, Australia; Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, PR China. Electronic address: younan.chen@curtin.edu.au.
authors: Younan
authors: Y
authors: Chen
authors: School of Biomedical Sciences, CHIRI Biosciences, Curtin University, GPO Box U1987, Perth, Western Australia, Australia.
authors: Rodrigo
authors: R
authors: Carlessi
authors: School of Biomedical Sciences, CHIRI Biosciences, Curtin University, GPO Box U1987, Perth, Western Australia, Australia.
authors: Nikita
authors: N
authors: Walz
authors: School of Biomedical Sciences, CHIRI Biosciences, Curtin University, GPO Box U1987, Perth, Western Australia, Australia.
authors: Vinicius Fernandes
authors: VF
authors: Cruzat
authors: School of Biomedical Sciences, CHIRI Biosciences, Curtin University, GPO Box U1987, Perth, Western Australia, Australia.
authors: Kevin
authors: K
authors: Keane
authors: Harry Perkins Institute of Medical Research, Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: Abraham N
authors: AN
authors: John
authors: Harry Perkins Institute of Medical Research, Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: Fang-Xu
authors: FX
authors: Jiang
authors: School of Pharmacy, CHIRI Biosciences, Curtin University, GPO Box U1987, Perth, Western Australia, Australia.
authors: Revathy
authors: R
authors: Carnagarin
authors: School of Pharmacy, CHIRI Biosciences, Curtin University, GPO Box U1987, Perth, Western Australia, Australia.
authors: Crispin R
authors: CR
authors: Dass
authors: School of Biomedical Sciences, CHIRI Biosciences, Curtin University, GPO Box U1987, Perth, Western Australia, Australia. Electronic address: philip.newsholme@curtin.edu.au.
authors: Philip
authors: P
authors: Newsholme
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002460:Cell Line; D004734:Energy Metabolism; D005136:Eye Proteins / Q000502:physiology*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000502:physiology*; D019308:Palmitic Acid / Q000494:pharmacology; D051381:Rats; D015843:Serpins / Q000502:physiology*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D000255:Adenosine Triphosphate; D005136:Eye Proteins; D005947:Glucose; D007328:Insulin; D009414:Nerve Growth Factors; D019308:Palmitic Acid; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor
keywords: ATGL; Insulin; Lipolysis; Metabolism; Pigment epithelium-derived factor; β-Cell