Disease relevance of Ppy

• Influence of a transplantable insulinoma on the pancreatic status of insulin and pancreatic polypeptide in the rat [1].
• Thus, at least 90% of the PP response to hypoglycemia is neurally mediated [2].
• Changes consisted of pronounced insulin cell hyperplasia, disarrangement of islet architecture, and disappearance (degranulation?) of a new islet cell type, the pancreatic polypeptide cell [3].
• Pancreatic polypeptide administration increased hepatic Bmax in rats with chronic pancreatitis (to 47.2 +/- 9.8 fmol/mg protein), but had no significant effect in sham-operated rats [4].
• For this purpose, either PP dissolved in saline (225, 450, or 900 pmol/kg body weight/h) or saline alone was infused at a rate of 2 ml/h for 30 min [5].

Psychiatry related information on Ppy

• We speculate, based on the patterns of binding in the olfactory and limbic systems, that PP receptors might be involved in positive reinforcement of ingestion behavioral as well as modulation of gastrointestinal function [6].

High impact information on Ppy

• A massive neuronal system was detected by immunocytochemistry and radioimmunoassay with antibodies to neuropeptide Y, the recently isolated peptide of the pancreatic polypeptide family [7].
• In activin-treated cells, mRNA for pancreatic polypeptide (PP) but not that for either insulin or glucagon was detected by reverse transcription-PCR [8].
• The mRNAs for insulin, PP, glucose transporter 2, and glucokinase, but not glucagon, were detected [8].
• The developmental origin of the four phenotypically distinct hormone-producing islet cells (insulin, glucagon, somatostatin, pancreatic polypeptide) is unclear [9].
• BACKGROUND/AIMS: Pancreatic polypeptide (PP), a hormone released from the pancreas, inhibits pancreatic secretion in vivo but not in vitro, suggesting that the inhibitory action of PP on pancreatic secretion is indirect [10].

Chemical compound and disease context of Ppy

• In control rats (n = 10), plasma PP increased from a baseline level of 30 +/- 3 pg/ml to 271 +/- 41 pg/ml during hypoglycemia (plasma glucose = 29 +/- 2 mg/dl) (delta PP = +241 +/- 42 pg/ml, P less than 0.0005), demonstrating that in rats, as in other species, insulin-induced hypoglycemia is a potent stimulus for PP release [2].
• The combination of combined blockade + atropine resulted in a PP response (delta = +26 +/- 7 pg/ml) to hypoglycemia that was similar to that in hexamethonium-treated rats (P less than 0.01 vs. control rats) [2].
• PP only increased by 31 +/- 10 pg/ml during similar hypoglycemia in 7 hexamethonium-treated rats (P less than 0.01 vs. control animals) [2].
• The plasma PP response to hypoglycemia was +85 +/- 24 pg/ml in atropine-treated rats (P 0.01 vs. control rats), suggesting that approximately 65% of the PP response is mediated via muscarinic acetylcholine receptors on the islet F cell [2].
• Effective pancreas denervation was documented by a decreased pancreatic polypeptide (PP) response to insulin-induced hypoglycemia and by decreased levels of norepinephrine and calcitonin gene-related peptide (CGRP) in pancreatic tissue [11].

Biological context of Ppy

• Nucleotide and amino acid sequences of the signal peptide and the pancreatic polypeptide of the rat were highly homologous to those of the human (Boel, E., Schwartz, T. W., Norris, K. E., and Fill, N. P. (1984) EMBO J. 3, 909-912) [12].
• Exon 2 of the rat gene encodes the signal peptide and pancreatic polypeptide, exon 3 encodes the carboxyl-terminal region, and exons 1 and 4 encode the 5'- and 3'- untranslated regions of the mRNA, respectively [13].
• We isolated cDNA clones encoding rat pancreatic polypeptide precursor from an islet cDNA library and determined their nucleic acid sequences [12].
• Available evidence indicates that the mosaicism of structural conservation and divergence in pancreatic polypeptide genes may have been caused by a difference in the evolutionary rates of the genomic regions [13].
• To understand the molecular basis of this divergence and conservation, we determined the nucleotide sequence of the rat pancreatic polypeptide gene from an islet genomic library and compared it with that of the human gene [13].

Anatomical context of Ppy

• Pancreatic polypeptide, a 36-amino acid peptide hormone, is synthesized in pancreatic islets of Langerhans and acts as a regulator of pancreatic and gastrointestinal functions [12].
• We investigated the pre- and postsynaptic effects of pancreatic polypeptide (PP) on identified pancreas-projecting neurons of the rat dorsal motor nucleus of the vagus in thin brain stem slices [14].
• PP induced a concentration-dependent inhibition in amplitude of excitatory (n = 22 of 30 neurons) and inhibitory (n = 13 of 17 neurons) postsynaptic currents evoked by electrical stimulation of the adjacent nucleus of the solitary tract, with an estimated EC(50) of 30 nM for both [14].
• Regardless of the PP-induced effect, the vast majority of responsive neurons had a multipolar somata morphology with dendrites projecting to areas other than the fourth ventricle or the central canal [14].
• In addition, the main source of PP to the systemic circulation may be the ventral part of the pancreas [15].

Associations of Ppy with chemical compounds

• Vasoactive intestinal polypeptide (10(-7) M) stimulated a weak PP secretion that was not inhibited by atropine [15].
• RESULTS: Microinjection of PP to the dorsal motor nucleus but not brainstem sites outside it inhibited 2-deoxy-D-glucose-stimulated pancreatic flow and protein output [10].
• The release of PP from the dorsal part of the rat pancreas by GRP and carbachol was also studied [15].
• Neuromedin C had almost the same bioactivity as GRP with respect to the release of PP, whereas neuromedin B was one-third less potent than GRP and neuromedin C [15].
• The results suggest that T3, 9-cis RA, and PP activate genes that regulate cell proliferation in target cells through receptor-mediated pathways and initiate cellular DNA synthesis [16].

Other interactions of Ppy

• Peptide YY (PYY) elicited a response that was similar in magnitude but with an ED50 (+/- SE, n = 3) of 0.76 +/- 0.24 micrograms/kg while porcine pancreatic polypeptide (pPP) was inactive when tested at 40 micrograms/kg (n = 4) [17].
• Spinal and peripheral modulation of gastric acid secretion and arterial pressure by neuropeptide Y, peptide YY, and pancreatic polypeptide in rats [18].
• Serial sections demonstrate that cells staining strongly for N-CAM in the splenic part correspond to glucagon cells and in the duodenal part to pancreatic polypeptide cells [19].
• Dynorphin (1-8) and enkephalin antisera stained the greatest number of cells, followed by FMRF-NH2, neurotensin, somatostatin and avian pancreatic polypeptide [20].
• The size and area of JIB islets were unchanged from controls as was the distribution of insulin, glucagon, somatostatin and pancreatic polypeptide [21].

Analytical, diagnostic and therapeutic context of Ppy

• Perfusion with PP induced a TTX- and apamin-sensitive, concentration-dependent outward (22% of neurons) or inward current (21% of neurons) that was accompanied by a decrease in input resistance; PP was also found to affect the amplitude of the action potential afterhyperpolarization [14].
• Pancreatic polypeptide microinjection into the dorsal motor nucleus inhibits pancreatic secretion in rats [10].
• The inhibitory effect of PP on CCK-8-stimulated protein output was eliminated by vagotomy [10].
• Immunohistochemistry demonstrated the presence of insulin, glucagon, somatostatin and pancreatic polypeptide within islet cells in long term grafts [22].
• Twenty days after subcutaneous transplantation, tumour-bearing rats exhibited marked hyperinsulinaemia and hypoglycaemia, with plasma pancreatic polypeptide concentrations similar to controls [1].

References