Journal article
Perilipin 2 downregulation in β cells impairs insulin secretion under nutritional stress and damages mitochondria
JCI insight, Vol.6(9), e144341
03/30/2021
DOI: 10.1172/jci.insight.144341
PMID: 33784258
Abstract
Perilipin 2 (PLIN2) is the lipid droplet (LD) protein in β cells that increases under nutritional stress. Down-regulation of PLIN2 is often sufficient to reduce LD accumulation. To determine whether PLIN2 positively or negatively affects β cell function under nutritional stress, PLIN2 was down-regulated in mouse β cells, INS1 cells, and human islet cells. β cell specific deletion of PLIN2 in mice on a high fat diet reduced glucose-stimulated insulin secretion (GSIS) in vivo and in vitro. Down-regulation of PLIN2 in INS1 cells blunted GSIS after 24 h incubation with 0.2 mM palmitic acids. Down-regulation of PLIN2 in human pseudoislets cultured at 5.6 mM glucose impaired both phases of GSIS, indicating that PLIN2 is critical for GSIS. Down-regulation of PLIN2 decreased specific OXPHOS proteins in all three models and reduced oxygen consumption rates in INS1 cells and mouse islets. Moreover, we found that PLIN2 deficient INS1 cells increased the distribution of a fluorescent oleic acid analog to mitochondria and showed signs of mitochondrial stress as indicated by susceptibility to fragmentation and alterations of acyl-carnitines and glucose metabolites. Collectively, PLIN2 in β cells have an important role in preserving insulin secretion, β cell metabolism, and mitochondrial function under nutritional stress.
Details
- Title: Subtitle
- Perilipin 2 downregulation in β cells impairs insulin secretion under nutritional stress and damages mitochondria
- Creators
- Akansha Mishra - Department of Internal Medicine, University of Iowa, Iowa City, United States of AmericaSiming Liu - Department of Internal Medicine, University of Iowa, Iowa City, United States of AmericaJoseph Promes - Department of Internal Medicine, University of Iowa, Iowa City, United States of AmericaMikako Harata - Department of Internal Medicine, University of Iowa, Iowa City, United States of AmericaWilliam I Sivitz - Department of Internal Medicine, University of Iowa, Iowa City, United States of AmericaBrian D Fink - Department of Internal Medicine, University of Iowa, Iowa City, United States of AmericaGourav Bhardwaj - Department of Internal Medicine, University of Iowa, Iowa City, United States of AmericaBrian T O'Neill - Department of Endocrinology, University of Iowa, Iowa City, United States of AmericaChen Kang - Department of Internal Medicine, Washington University School of Medicine, Saint Louis, United States of AmericaRajan Sah - Department of Internal Medicine, Washington University School of Medicine, Saint Louis, United States of AmericaStefan Strack - Department of Pharmacology and Neuroscience, University of Iowa, Iowa City, United States of AmericaSamuel B Stephens - Department of Internal Medicine, University of Iowa, Iowa City, United States of AmericaTimothy H King - Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, United States of AmericaLaura Jackson - Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, United States of AmericaAndrew S Greenberg - Obesity and Metabolism Laboratory, Tufts University, Boston, United States of AmericaFrederick Anokye-Danso - Department of Medicine, Johns Hopkins School of Medicine, Baltimore, United States of AmericaRexford S Ahima - Department of Medicine, Johns Hopkins School of Medicine, Baltimore, United States of AmericaJames A Ankrum - Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, United States of AmericaYumi Imai - Department of Internal Medicine, University of Iowa, Iowa City, United States of America
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.6(9), e144341
- DOI
- 10.1172/jci.insight.144341
- PMID
- 33784258
- NLM abbreviation
- JCI Insight
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Publisher
- United States
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01-DK090490, DK046200-23, DK046200-27S2, DK108722 01A1, 1R21HD098056-01, 2UC4DK098085, 1 S10 RR025439-01; DOI: 10.13039/100000005, name: U.S. Department of Defense, award: lO1 BXOO4468; DOI: 10.13039/100000199, name: USDA, award: 1950-51000-071-02S
- Language
- English
- Date published
- 03/30/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984068230702771
Metrics
26 Record Views