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Characterization of a Novel Functional Protein in the Pancreatic Islet: Islet Homeostasis Protein Regulation of Glucagon Synthesis in Cells

Oh, Seh-Hoon PhD*; Darwiche, Houda PhD; Cho, Jae-Hyoung MD; Shupe, Thomas PhD*; Petersen, Bryon E. PhD*

Pancreas:
doi: 10.1097/MPA.0b013e3182222ee5
Original Articles
Abstract

Objective: We have identified a novel protein in bone marrow–derived insulin-producing cells. Here we characterize this protein, hereby named islet homeostasis protein (IHoP), in the pancreatic islet.

Methods: Detection of IHoP mRNA and protein was performed using reverse transcriptase–polymerase chain reaction, immunocytochemistry, and in situ hybridization. Islet homeostasis protein functions were utilizing proliferation, insulin secretion by in vitro assays, and following small interfering RNA protocols for suppression of IHoP.

Results: We found that IHoP did not homolog with known pancreatic hormones. Islet homeostasis protein expression was seen in both bone marrow–derived insulin-producing cells and isolated pancreatic islets. Immunohistochemistry on pancreatic islet revealed that IHoP localized to the glucagon-synthesizing α cells. Inhibition of IHoP by small interfering RNA resulted in the loss of glucagon expression, which induced low blood glucose levels (63–85 mg/dL). Subsequently, cellular apoptosis was observed throughout the islet, including the insulin-producing β cells. Islets of preonset diabetic patients showed normal expression of IHoP and glucagon; however, IHoP was lost upon onset of the disease.

Conclusions: These data suggest that IHoP could be a new functional protein in the islet and may play a role in islet homeostasis.

Abbreviations: IHoP - islet homeostasis protein, BM - bone marrow, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

Author Information

From the *Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC; †Sciences for Health Programs, Santa Fe College, Gainesville, FL; and ‡Department of Internal Medicine, Kangnam St Mary Hospital, The Catholic University of Korea, Seoul, South Korea.

Received for publication February 17, 2011; accepted April 29, 2011.

Reprints: Seh-Hoon Oh, PhD, Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (e-mail: soh@wfubmc.edu).

This work was supported by National Institute of Health grants DK60015 and DK58614 awarded to BEP.

S.H.O. and B.E.P. are inventor/coinventor of a patent(s) related to this technology and may benefit from royalties paid to the University of Florida related to its commercialization.

© 2012 Lippincott Williams & Wilkins, Inc.