Tripeptide Amide L-pyroglutamyl-Histidyl-L-Prolineamide (L-PHPThyrotropin- Releasing Hormone, TRH) Promotes Insulin-Producing Cell Proliferation
John ZQ Luo,
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.
Keywords: Diabetes, neural tripeptide amide.
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