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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #386182
Research Project: Energy Met.: Novel Approaches to Facilitating Successful Energy Regulation in Aging--Obesity & Met.: Role of Adipocyte Metabolism in the Development of Obesity and Associated Metabolic Complications

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: Perilipin 2 downregulation in Beta cells impairs insulin secretion under nutritional stress and damages mitochondria

Author
item MISHRA, AKANSHA - UNIVERSITY OF IOWA
item LIU, SIMING - UNIVERSITY OF IOWA
item PROMES, JOSEPH - UNIVERSITY OF IOWA
item HARATA, MIKAKO - UNIVERSITY OF IOWA
item SIVITZ, WILLIAM - UNIVERSITY OF IOWA
item FINCK, BRIAN - WASHINGTON UNIVERSITY SCHOOL OF MEDICINE
item BHARDWAJ, GOURAV - UNIVERSITY OF IOWA
item O'NEILL, BRIAN - UNIVERSITY OF IOWA HOSPITALS AND CLINICS
item KANG, CHEN - WASHINGTON UNIVERSITY SCHOOL OF MEDICINE
item SAH, RAJAH - WASHINGTON UNIVERSITY SCHOOL OF MEDICINE
item STRACK, STEFAN - UNIVERSITY OF IOWA
item STEPHENS, SAMUEL - UNIVERSITY OF IOWA
item KING, TIMOTHY - EASTERN VIRGINIA MEDICAL SCHOOL
item JACKSON, LAURA - EASTERN VIRGINIA MEDICAL SCHOOL
item GREENBERG, ANDREW - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY
item ANOKEY-DANSO, FREDERICK - JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE
item AHIMA, REXFORD - JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE
item ANKRUM, JAMES - UNIVERSITY OF IOWA
item LAMI, YUMI - UNIVERSITY OF IOWA

Submitted to: Journal of Clinical Investigation Insight
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/24/2021
Publication Date: 5/10/2021
Citation: Mishra, A., Liu, S., Promes, J., Harata, M., Sivitz, W.I., Finck, B., Bhardwaj, G., O'Neill, B., Kang, C., Sah, R., Strack, S., Stephens, S., King, T., Jackson, L., Greenberg, A., Anokey-Danso, F., Ahima, R.S., Ankrum, J., Lami, Y. 2021. Perilipin 2 downregulation in Beta cells impairs insulin secretion under nutritional stress and damages mitochondria. Journal of Clinical Investigation Insight. 6(9):e144341. https://doi.org/10.1172/jci.insight.144341.
DOI: https://doi.org/10.1172/jci.insight.144341

Interpretive Summary: In this paper we demonstrate expression of the protein perilipin 2 in the islet cells of the pancreas (the cells that make insulin) with high fat feeding is important in maintaining the ability of islet cells to secrete insulin at appropriate levels.

Technical Abstract: Perilipin 2 (PLIN2) is the lipid droplet (LD) protein in beta cells that increases under nutritional stress. Downregulation of PLIN2 is often sufficient to reduce LD accumulation. To determine whether PLIN2 positively or negatively affects Beta cell function under nutritional stress, PLIN2 was downregulated in mouse beta cells, INS1 cells, and human islet cells. Beta Cell-specific deletion of PLIN2 in mice on a high-fat diet reduced glucose-stimulated insulin secretion (GSIS) in vivo and in vitro. Downregulation of PLIN2 in INS1 cells blunted GSIS after 24-hour incubation with 0.2 mM palmitic acid. Downregulation of PLIN2 in human pseudoislets cultured at 5.6 mM glucose impaired both phases of GSIS, indicating that PLIN2 is critical for GSIS. Downregulation of PLIN2 decreased specific OXPHOS proteins in all 3 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 beta cells has an important role in preserving insulin secretion, beta cell metabolism and mitochondrial function under nutritional stress.