title: Tripeptide amide L-pyroglutamyl-histidyl-L-prolineamide (L-PHP-thyrotropin-releasing hormone, TRH) promotes insulin-producing cell proliferation.
abstract: A very small tripeptide amide L-pyroglutamyl-L-histidyl-L-prolineamide (L-PHP, Thyrotropin-Releasing Hormone, TRH), was first identified in the brain hypothalamus area. Further studies found that L-PHP was expressed in pancreas. The biological role of pancreatic L-PHP is still not clear. Growing evidence indicates that L-PHP expression in the pancreas may play a pivotal role for pancreatic development in the early prenatal period. However, the role of L-PHP in adult pancreas still needs to be explored. L-PHP activation of pancreatic β cell Ca2+ flow and stimulation of β-cell insulin synthesis and release suggest that L-PHP involved in glucose metabolism may directly act on the β cell separate from any effects via the central nervous system (CNS). Knockout L-PHP animal models have shown that loss of L-PHP expression causes hyperglycemia, which cannot be reversed by administration of thyroid hormone, suggesting that the absence of L-PHP itself is the cause. L-PHP receptor type-1 has been identified in pancreas which provides a possibility for L-PHP autocrine and paracrine regulation in pancreatic function. During pancreatic damage in adult pancreas, L-PHP may protect beta cell from apoptosis and initiate its regeneration through signal pathways of growth hormone in β cells. L-PHP has recently been discovered to affect a broad array of gene expression in the pancreas including growth factor genes. Signal pathways linked between L-PHP and EGF receptor phosphorylation suggest that L-PHP may be an important factor for adult β-cell regeneration, which could involve adult stem cell differentiation. These effects suggest that L-PHP may benefit pancreatic β cells and diabetic therapy in clinic.
authors.affiliation: Department Research, Center of Stem Cell Research, Roger Williams Hospital, Providence, Rhode Island 02908, USA. Lluo@rwmc.org
authors.forename: LuGuang
authors.initials: L
authors.lastname: Luo
authors.forename: John Z Q
authors.initials: JZ
authors.lastname: Luo
authors.forename: Ivor
authors.initials: I
authors.lastname: Jackson
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D010179:Pancreas / Q000502:physiology; D051381:Rats; D015398:Signal Transduction; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000502:physiology*
chemical_list: D007328:Insulin; D013973:Thyrotropin-Releasing Hormone; D066246:ErbB Receptors