Pigment epithelium-derived factor (PEDF) regulates metabolism and insulin secretion from a clonal rat pancreatic beta cell line BRIN-BD11 and mouse islets

Younan Chen; Rodrigo Carlessi; Nikita Walz; Vinicius Fernandes Cruzat; Kevin Keane; Abraham N. John; Fang Xu Jiang; Revathy Carnagarin; Crispin R. Dass; Philip Newsholme

doi:10.1016/j.mce.2016.02.004

Pigment epithelium-derived factor (PEDF) regulates metabolism and insulin secretion from a clonal rat pancreatic beta cell line BRIN-BD11 and mouse islets

Younan Chen, Rodrigo Carlessi, Nikita Walz, Vinicius Fernandes Cruzat, Kevin Keane, Abraham N. John, Fang Xu Jiang, Revathy Carnagarin, Crispin R. Dass, Philip Newsholme

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

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.

Original language	English
Pages (from-to)	50-60
Number of pages	11
Journal	Molecular and Cellular Endocrinology
Volume	426
DOIs	https://doi.org/10.1016/j.mce.2016.02.004
Publication status	Published - 5 May 2016
Externally published	Yes

Keywords

ATGL
Insulin
Lipolysis
Metabolism
Pigment epithelium-derived factor
β-Cell

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10.1016/j.mce.2016.02.004

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Chen, Y., Carlessi, R., Walz, N., Cruzat, V. F., Keane, K., John, A. N., Jiang, F. X., Carnagarin, R., Dass, C. R., & Newsholme, P. (2016). Pigment epithelium-derived factor (PEDF) regulates metabolism and insulin secretion from a clonal rat pancreatic beta cell line BRIN-BD11 and mouse islets. Molecular and Cellular Endocrinology, 426, 50-60. https://doi.org/10.1016/j.mce.2016.02.004

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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.",

keywords = "ATGL, Insulin, Lipolysis, Metabolism, Pigment epithelium-derived factor, β-Cell",

author = "Younan Chen and Rodrigo Carlessi and Nikita Walz and Cruzat, {Vinicius Fernandes} and Kevin Keane and John, {Abraham N.} and Jiang, {Fang Xu} and Revathy Carnagarin and Dass, {Crispin R.} and Philip Newsholme",

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Chen, Y, Carlessi, R, Walz, N, Cruzat, VF, Keane, K, John, AN, Jiang, FX, Carnagarin, R, Dass, CR & Newsholme, P 2016, 'Pigment epithelium-derived factor (PEDF) regulates metabolism and insulin secretion from a clonal rat pancreatic beta cell line BRIN-BD11 and mouse islets', Molecular and Cellular Endocrinology, vol. 426, pp. 50-60. https://doi.org/10.1016/j.mce.2016.02.004

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T1 - Pigment epithelium-derived factor (PEDF) regulates metabolism and insulin secretion from a clonal rat pancreatic beta cell line BRIN-BD11 and mouse islets

AU - Chen, Younan

AU - Carlessi, Rodrigo

AU - Walz, Nikita

AU - Cruzat, Vinicius Fernandes

AU - Keane, Kevin

AU - John, Abraham N.

AU - Jiang, Fang Xu

AU - Carnagarin, Revathy

AU - Dass, Crispin R.

AU - Newsholme, Philip

PY - 2016/5/5

Y1 - 2016/5/5

N2 - 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.

AB - 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.

KW - ATGL

KW - Insulin

KW - Lipolysis

KW - Metabolism

KW - Pigment epithelium-derived factor

KW - β-Cell

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ER -

Pigment epithelium-derived factor (PEDF) regulates metabolism and insulin secretion from a clonal rat pancreatic beta cell line BRIN-BD11 and mouse islets

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Keywords

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