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Glucagon synthesizing alpha‐cells secret Islet Homeostasis protein (IHoP) for regulation of hormone synthesis and proliferation of insulin producing beta‐cells
Author(s) -
Oh Seh-Hoon,
Petersen Bryon E
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1034.11
Subject(s) - glucagon , islet , glucose homeostasis , homeostasis , insulin , immunocytochemistry , alpha cell , beta cell , pancreatic islets , hormone , endocrinology , medicine , microbiology and biotechnology , chemistry , biology , insulin resistance
Objective We have identified a novel protein in bone marrow‐derived insulin‐producing cells. We now characterize a role for this protein, termed Islet Homeostasis Protein (IHoP), in the pancreatic islet. Methods Detection of IHoP was performed using RT‐PCR, immunocytochemistry and in‐situ hybridization. IHoP functions were utilizing proliferation, insulin secretion by in vitro assays, and following siRNA protocols for suppression of IHoP. Results IHoP did not homologue with known pancreatic hormones. IHoP expression was seen in both BM‐derived IPCs and isolated pancreatic islets. Immunohistochemistry on pancreatic islet revealed that IHoP localized to the glucagon synthesizing alpha‐cells. Inhibition of IHoP by siRNA resulted in the loss of glucagon expression, which induced low blood glucose levels (63–85mg/dL). IHoP is secreted from the glucagon synthesizing α‐cells, and that it has a role in regulating cellular proliferation of beta‐cell under high glucose conditions. Subsequently, cellular apoptosis was observed throughout the islet, including the insulin‐producing beta‐cells. Islets of pre‐onset diabetic patients showed normal expression of IHoP and glucagon; however IHoP was lost upon onset of the disease. Conclusion These data suggest that IHoP could be a new functional protein required in the homeostasis of the islet and it may also play a role in our understanding of T1D progression.