Perilipin 5 regulates islet lipid metabolism and insulin secretion in a cAMP-dependent manner: implication of its role in the postprandial insulin secretion

Diabetes. 2015 Apr;64(4):1299-310. doi: 10.2337/db14-0559. Epub 2014 Nov 12.


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 [(3)H]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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cyclic AMP / metabolism*
  • Fasting / metabolism
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Islets of Langerhans / metabolism*
  • Lipid Metabolism / physiology*
  • Lipolysis / physiology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Perilipin-2
  • Postprandial Period / physiology*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism


  • Ffar1 protein, mouse
  • Insulin
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Muscle Proteins
  • PLIN2 protein, human
  • Perilipin-2
  • Plin2 protein, mouse
  • Receptors, G-Protein-Coupled
  • lipid storage droplet protein 5, mouse
  • Cyclic AMP
  • Glucose