Disease relevance of Ppy

• We examined the role of PP in the regulation of body weight as well as the therapeutic potential of PP [1].
• In contrast, PP cell volume density remained stable throughout, suggesting that this cell type kept pace with B cell hyperplasia [2].
• 2) During neuroglucopenia or hypoglycemia, plasma PP is increased via nicotinic and muscarinic mechanisms [3].
• Obesity can be reversed in ob/ob mice by parabiosis to lean littermates, by islet transplantation, and by injection of pancreatic polypeptide [4].
• Pancreatic polypeptide was infused into obese-hyperglycemic (ob/ob) mice and lean littermates to determine its effect on weight gain [5].

Psychiatry related information on Ppy

• The feeding response to PP family peptides were quite similar to that in locomotor activity with respect to dose-response, time course and peptide specificity [6].
• Furthermore, PP secretion in response to CCK-8 showed a similarity with that of insulin in terms of dose- and time-response characteristics as well as sensitivity to CCKA-receptor antagonism [7].

High impact information on Ppy

• Immunocytochemistry detected the presence of insulin, glucagon, pancreatic polypeptide and somatostatin-producing cells organized into islet clusters; immuno-electron microscopy showed typical insulin-containing granules [8].
• Y4(-/-) mice displayed lower body weight and reduced white adipose tissue mass accompanied by increased plasma levels of pancreatic polypeptide (PP) [9].
• Liver enzyme abnormalities in FLS-ob/ob obese mice were also ameliorated by PP [1].
• METHODS: We measured food intake, gastric emptying, oxygen consumption, and gene expression of hypothalamic neuropeptides, gastric ghrelin, and adipocytokines in mice after administering PP intraperitoneally [1].
• The expression of gastric ghrelin and hypothalamic orexin was decreased in PP-overexpressing mice [1].

Chemical compound and disease context of Ppy

• Neuroglucopenia induced by 2-deoxy-D-glucose or insulin-induced hypoglycemia also increased plasma PP (+79 +/- 18 and +89 +/- 11 pg/ml vs. control, respectively) [3].

Biological context of Ppy

• CONCLUSIONS: These observations indicate that PP may influence food intake, energy metabolism, and the expression of hypothalamic peptides and gastric ghrelin [1].
• RESULTS: Peripherally administered PP induced negative energy balance by decreasing food intake and gastric emptying while increasing energy expenditure [1].
• Peptide gene expression was also examined in PP-overexpressing mice [1].
• Embryogenesis of the murine endocrine pancreas; early expression of pancreatic polypeptide gene [10].
• PP had no effect on blood pressure or cardiac vagal activity in either group of mice, which was consistent with earlier studies in other species [11].

Anatomical context of Ppy

• These results suggest an intriguing ontogenic relationship between A- and PP-cells, and also indicate that PP-containing cells may occupy a hitherto unexpected place in the lineage of endocrine islet cells [10].
• Many of these cells contain both glucagon and PP which, by immunogold labelling of consecutive thin sections, can be shown to co-exist within individual secretory granules [10].
• Mechanisms of neuropeptide Y, peptide YY, and pancreatic polypeptide inhibition of identified green fluorescent protein-expressing GABA neurons in the hypothalamic neuroendocrine arcuate nucleus [12].
• These results also suggest that pancreatic polypeptide gene-expressing cells are indispensable for the differentiation of islet beta and delta cells because the former produce a necessary paracrine or endocrine factor and/or operate through a cell-lineage relationship [13].
• Germ-line Y2 receptor knockout also produced a significant increase in plasma levels of pancreatic polypeptide [14].

Associations of Ppy with chemical compounds

• The endogenous Y4 agonist PP depressed the activity of GABA-expressing neurons mainly by presynaptic attenuation of glutamate release [12].
• GIP and PP did not change IPNA-induced insulin release [15].
• Plasma concentrations of pancreatic polypeptide and corticosterone were 3- to 5-fold increased in hypothalamus-specific Y2 knockout mice [14].
• Impaired glucose tolerance in pancreatic polypeptide-overexpressing mice [16].
• Most PP-cells reacted to carbachol and epinephrine with prompt and reversible elevation of [Ca2+]i, often manifested as slow oscillations [17].

Regulatory relationships of Ppy

• 60% of pancreatic polypeptide (PP)-cells expressed sst4 in both groups [18].

Other interactions of Ppy

• NPY (0.3-10 micrograms), PYY (0.1-10 micrograms) and PP (3.0-10 micrograms) produced significant increases in locomotor activity [6].
• NPY appeared later and occurred exclusively in a subpopulation of insulin cells, whereas PP cells arose latest [19].
• The islets of Langerhans contain four distinct endocrine cell types producing the hormones glucagon, insulin, somatostatin and pancreatic polypeptide [20].
• 5. Expression of Ngn3 and pancreatic polypeptide marks endocrine cell lineages during early embryogenesis, and these cells behave as transient progenitors rather than stem cells [21].
• Effects of cholecystokinin and glucagon-like peptide 1 on the secretion of pancreatic polypeptide in mice [7].

Analytical, diagnostic and therapeutic context of Ppy

• By immunofluorescence on cytospin preparations and on semithin sections of mouse pancreatic buds, we have found glucagon and pancreatic polypeptide (PP)-containing cells at embryonal day 10.5 (E 10.5) in dorsal buds and at E 11.5 in ventral buds [10].
• By PCR amplification of oligo(dT)-primed cDNAs prepared from total pancreatic RNA, we also detect PP mRNA from E 10.5 onwards, thus confirming the early expression of the PP gene in the developing mouse pancreas [10].
• In conclusion, this study, using a newly developed radioimmunoassay for PP in rodents, shows that CCK-8 but not GPL-1 stimulated PP secretion in mice at dose levels where both peptides stimulate insulin secretion [7].
• Pancreatic spasmolytic Polypeptide (PSP) is a new porcine pancreatic polypeptide, which inhibits gastrointestinal motility and gastric acid secretion in laboratory animals after parenteral as well as oral administration [22].
• Immunohistochemistry and double-immunofluorescence studies using a specific antibody revealed the predominant Gpr119 localization in pancreatic polypeptide (PP)-cells of islets [23].

References