title: Characterization of a novel functional protein in the pancreatic islet: islet homeostasis protein regulation of glucagon synthesis in α cells.
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.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. soh@wfubmc.edu
authors.forename: Seh-Hoon
authors.initials: SH
authors.lastname: Oh
authors.forename: Houda
authors.initials: H
authors.lastname: Darwiche
authors.forename: Jae-Hyoung
authors.initials: JH
authors.lastname: Cho
authors.forename: Thomas
authors.initials: T
authors.lastname: Shupe
authors.forename: Bryon E
authors.initials: BE
authors.lastname: Petersen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005934:Glucagon / Q000096:biosynthesis* / Q000494:pharmacology; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007328:Insulin / Q000096:biosynthesis; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007328:Insulin; D011506:Proteins; C572216:Tbc1d8 protein, rat; D005934:Glucagon; D005947:Glucose