**1. Introduction**

Neural tripeptide amide L-pyroglutamyl-L-histidyl-L-prolineamide (L-PHP, Thyrotropinreleasing hormone, TRH) is a fine molecular peptide that was first identified in the Central Nervous System (CNS) and discovered in many other regions of body later as a neuropeptide hormone or neuromodulator [1]. L-PHP stimulates the thyroid stimulating hormone (TSH) after it is released from the hypothalamic nerve in the median eminence. L-PHP was named as its functional action-TRH [2]. Beyond neuronal tissue, expression of L-PHP was also found in the pancreatic islets where it identifies to the Langerhans-insulin-producing beta cells [3]. However, L-PHP expression and production is significantly different from its production in the nervous system; it is primarily expressed during the early developmental period in rat [4] and human fetal pancreatic tissue [4]. L-PHP stimulates glucagon release and inhibits other pancreatic secretion other than TSH [5]. In this review, based on evidence found in L-PHP gene knockout animal models and its function in regulating insulin release in pancreatic tissue [6], L-PHP may play an important role in carbohydrate metabolism and pancreatic L-PHP disruption may lead to the development of diabetes mellitus.

Expression of L-PHP in the pancreas: L-PHP is expressed in the insulin granules of β cells in pancreatic islets, [7] with high levels during the neonatal period but significantly decreased as postnatal development progresses [4]. A Comparison with L-PHP expression, in the primary transition period between E12 and E14, shows insulin secretion in both rat and mouse while L-PHP remains unexpressed[4, 8]. During this period, insulin stained cells do not express any Rab3A, SNAP-25 (two molecules important for the control of insulin secretion) nor Glut 2 and

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granules resemble β cells. However, at E16, L-PHP expression was found and thereafter, high expression of molecules such as Glut2 and Pdx-1, which are necessary for insulin production, maturation and full insulin cell function, were found in the insulin and L-PHP positive cells. L-PHP's significant expression coincides with factors for insulin production, maturation and insulin cell development suggesting that L-PHP is critical for insulin cells as they become functionally mature during early development.
