Perilipin 5 regulates islet lipid metabolism and insulin secretion in a cAMP-dependent manner

Implication of its role in the postprandial insulin secretion

Michelle B. Trevino, Yui Machida, Daniel R. Hallinger, Eden Garcia, Aaron Christensen, Sucharita Dutta, David A. Peake, Yasuhiro H Ikeda, Yumi Imai

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Elevation of circulating fatty acids (FA) during fasting supports postprandial (PP) insulin secretion that is critical for glucose homeostasis and is impaired in diabetes. We tested our hypothesis that lipid droplet (LD) protein perilipin 5 (PLIN5) in β-cells aids PP insulin secretion by regulating intracellular lipid metabolism. We demonstrated that PLIN5 serves as an LD protein in human islets. In vivo, Plin5 and triglycerides were increased by fasting in mouse islets. MIN6 cells expressing PLIN5 (adenovirus [Ad]-PLIN5) and those expressing perilipin 2 (PLIN2) (Ad-PLIN2) had higher [3H]FA incorporation into triglycerides than Ad-GFP control, which support their roles as LD proteins. However, Ad-PLIN5 cells had higher lipolysis than Ad-PLIN2 cells, which increased further by 8-Br-cAMP, indicating that PLIN5 facilitates FA mobilization upon cAMP stimulation as seen postprandially. Ad-PLIN5 in islets enhanced the augmentation of glucose-stimulated insulin secretion by FA and 8-Br-cAMP in G-protein-coupled receptor 40 (GPR40)- and cAMP-activated protein kinase-dependent manners, respectively. When PLIN5 was increased in mouse β-cells in vivo, glucose tolerance after an acute exenatide challenge was improved. Therefore, the elevation of islet PLIN5 during fasting allows partitioning of FA into LD that is released upon refeeding to support PP insulin secretion in cAMP- and GPR40-dependent manners.

Original languageEnglish (US)
Pages (from-to)1299-1310
Number of pages12
JournalDiabetes
Volume64
Issue number4
DOIs
StatePublished - Apr 1 2015

Fingerprint

Lipid Metabolism
Insulin
Adenoviridae
Fatty Acids
Fasting
G-Protein-Coupled Receptors
Glucose
Triglycerides
Perilipin-5
Lipolysis
Cyclic AMP-Dependent Protein Kinases
Homeostasis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Perilipin 5 regulates islet lipid metabolism and insulin secretion in a cAMP-dependent manner : Implication of its role in the postprandial insulin secretion. / Trevino, Michelle B.; Machida, Yui; Hallinger, Daniel R.; Garcia, Eden; Christensen, Aaron; Dutta, Sucharita; Peake, David A.; Ikeda, Yasuhiro H; Imai, Yumi.

In: Diabetes, Vol. 64, No. 4, 01.04.2015, p. 1299-1310.

Research output: Contribution to journalArticle

Trevino, MB, Machida, Y, Hallinger, DR, Garcia, E, Christensen, A, Dutta, S, Peake, DA, Ikeda, YH & Imai, Y 2015, 'Perilipin 5 regulates islet lipid metabolism and insulin secretion in a cAMP-dependent manner: Implication of its role in the postprandial insulin secretion', Diabetes, vol. 64, no. 4, pp. 1299-1310. https://doi.org/10.2337/db14-0559
Trevino, Michelle B. ; Machida, Yui ; Hallinger, Daniel R. ; Garcia, Eden ; Christensen, Aaron ; Dutta, Sucharita ; Peake, David A. ; Ikeda, Yasuhiro H ; Imai, Yumi. / Perilipin 5 regulates islet lipid metabolism and insulin secretion in a cAMP-dependent manner : Implication of its role in the postprandial insulin secretion. In: Diabetes. 2015 ; Vol. 64, No. 4. pp. 1299-1310.
@article{c57db67905524c1eb43b45714fda0dd0,
title = "Perilipin 5 regulates islet lipid metabolism and insulin secretion in a cAMP-dependent manner: Implication of its role in the postprandial insulin secretion",
abstract = "Elevation of circulating fatty acids (FA) during fasting supports postprandial (PP) insulin secretion that is critical for glucose homeostasis and is impaired in diabetes. We tested our hypothesis that lipid droplet (LD) protein perilipin 5 (PLIN5) in β-cells aids PP insulin secretion by regulating intracellular lipid metabolism. We demonstrated that PLIN5 serves as an LD protein in human islets. In vivo, Plin5 and triglycerides were increased by fasting in mouse islets. MIN6 cells expressing PLIN5 (adenovirus [Ad]-PLIN5) and those expressing perilipin 2 (PLIN2) (Ad-PLIN2) had higher [3H]FA incorporation into triglycerides than Ad-GFP control, which support their roles as LD proteins. However, Ad-PLIN5 cells had higher lipolysis than Ad-PLIN2 cells, which increased further by 8-Br-cAMP, indicating that PLIN5 facilitates FA mobilization upon cAMP stimulation as seen postprandially. Ad-PLIN5 in islets enhanced the augmentation of glucose-stimulated insulin secretion by FA and 8-Br-cAMP in G-protein-coupled receptor 40 (GPR40)- and cAMP-activated protein kinase-dependent manners, respectively. When PLIN5 was increased in mouse β-cells in vivo, glucose tolerance after an acute exenatide challenge was improved. Therefore, the elevation of islet PLIN5 during fasting allows partitioning of FA into LD that is released upon refeeding to support PP insulin secretion in cAMP- and GPR40-dependent manners.",
author = "Trevino, {Michelle B.} and Yui Machida and Hallinger, {Daniel R.} and Eden Garcia and Aaron Christensen and Sucharita Dutta and Peake, {David A.} and Ikeda, {Yasuhiro H} and Yumi Imai",
year = "2015",
month = "4",
day = "1",
doi = "10.2337/db14-0559",
language = "English (US)",
volume = "64",
pages = "1299--1310",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "4",

}

TY - JOUR

T1 - Perilipin 5 regulates islet lipid metabolism and insulin secretion in a cAMP-dependent manner

T2 - Implication of its role in the postprandial insulin secretion

AU - Trevino, Michelle B.

AU - Machida, Yui

AU - Hallinger, Daniel R.

AU - Garcia, Eden

AU - Christensen, Aaron

AU - Dutta, Sucharita

AU - Peake, David A.

AU - Ikeda, Yasuhiro H

AU - Imai, Yumi

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Elevation of circulating fatty acids (FA) during fasting supports postprandial (PP) insulin secretion that is critical for glucose homeostasis and is impaired in diabetes. We tested our hypothesis that lipid droplet (LD) protein perilipin 5 (PLIN5) in β-cells aids PP insulin secretion by regulating intracellular lipid metabolism. We demonstrated that PLIN5 serves as an LD protein in human islets. In vivo, Plin5 and triglycerides were increased by fasting in mouse islets. MIN6 cells expressing PLIN5 (adenovirus [Ad]-PLIN5) and those expressing perilipin 2 (PLIN2) (Ad-PLIN2) had higher [3H]FA incorporation into triglycerides than Ad-GFP control, which support their roles as LD proteins. However, Ad-PLIN5 cells had higher lipolysis than Ad-PLIN2 cells, which increased further by 8-Br-cAMP, indicating that PLIN5 facilitates FA mobilization upon cAMP stimulation as seen postprandially. Ad-PLIN5 in islets enhanced the augmentation of glucose-stimulated insulin secretion by FA and 8-Br-cAMP in G-protein-coupled receptor 40 (GPR40)- and cAMP-activated protein kinase-dependent manners, respectively. When PLIN5 was increased in mouse β-cells in vivo, glucose tolerance after an acute exenatide challenge was improved. Therefore, the elevation of islet PLIN5 during fasting allows partitioning of FA into LD that is released upon refeeding to support PP insulin secretion in cAMP- and GPR40-dependent manners.

AB - Elevation of circulating fatty acids (FA) during fasting supports postprandial (PP) insulin secretion that is critical for glucose homeostasis and is impaired in diabetes. We tested our hypothesis that lipid droplet (LD) protein perilipin 5 (PLIN5) in β-cells aids PP insulin secretion by regulating intracellular lipid metabolism. We demonstrated that PLIN5 serves as an LD protein in human islets. In vivo, Plin5 and triglycerides were increased by fasting in mouse islets. MIN6 cells expressing PLIN5 (adenovirus [Ad]-PLIN5) and those expressing perilipin 2 (PLIN2) (Ad-PLIN2) had higher [3H]FA incorporation into triglycerides than Ad-GFP control, which support their roles as LD proteins. However, Ad-PLIN5 cells had higher lipolysis than Ad-PLIN2 cells, which increased further by 8-Br-cAMP, indicating that PLIN5 facilitates FA mobilization upon cAMP stimulation as seen postprandially. Ad-PLIN5 in islets enhanced the augmentation of glucose-stimulated insulin secretion by FA and 8-Br-cAMP in G-protein-coupled receptor 40 (GPR40)- and cAMP-activated protein kinase-dependent manners, respectively. When PLIN5 was increased in mouse β-cells in vivo, glucose tolerance after an acute exenatide challenge was improved. Therefore, the elevation of islet PLIN5 during fasting allows partitioning of FA into LD that is released upon refeeding to support PP insulin secretion in cAMP- and GPR40-dependent manners.

UR - http://www.scopus.com/inward/record.url?scp=84962020084&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962020084&partnerID=8YFLogxK

U2 - 10.2337/db14-0559

DO - 10.2337/db14-0559

M3 - Article

VL - 64

SP - 1299

EP - 1310

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -