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Pancreatic Polypeptide (pancreatic + polypeptide)

Distribution by Scientific Domains

Medical Sciences	81%

Selected Abstracts

Modulation of inhibitory neurotransmission in brainstem vagal circuits by NPY and PYY is controlled by cAMP levels

NEUROGASTROENTEROLOGY & MOTILITY, Issue 12 2009
K. N. Browning
Abstract, Pancreatic polypeptides such as neuropeptide Y (NPY) and peptide YY (PYY) exert profound, vagally mediated effects on gastrointestinal (GI) motility. Vagal efferent outflow to the GI tract is determined principally by tonic GABAergic synaptic inputs onto dorsal motor nucleus of the vagus (DMV) neurons, yet neither peptide modulates GABAergic transmission. We showed recently that opioid peptides appear similarly ineffective because of the low resting cAMP levels. Using whole cell recordings from identified DMV neurons, we aimed to correlate the influence of brainstem cAMP levels with the ability of pancreatic polypeptides to modulate GABAergic synaptic transmission. Neither NPY, PYY, nor the Y1 or Y2 receptor selective agonists [Leu,Pro]NPY or NPY(3-36) respectively, inhibited evoked inhibitory postsynaptic current (eIPSC) amplitude unless cAMP levels were elevated by forskolin or 8-bromo-cAMP, by exposure to adenylate cyclase-coupled modulators such as cholecystokinin octapeptide (sulfated) (CCK-8s) or thyrotropin releasing hormone (TRH), or by vagal deafferentation. The inhibition of eIPSC amplitude by [Leu,Pro]NPY or NPY(3-36) was stable for approximately 30 min following the initial increase in cAMP levels. Thereafter, the inhibition declined gradually until the agonists were again ineffective after 60 min. Analysis of spontaneous and miniature currents revealed that such inhibitory effects were due to actions at presynaptic Y1 and Y2 receptors. These results suggest that, similar to opioid peptides, the effects of pancreatic polypeptides on GABAergic transmission depend upon the levels of cAMP within gastric inhibitory vagal circuits. [source]

RESEARCH FOCUS ON COMPULSIVE BEHAVIOUR IN ANIMALS: Pre-exposure to environmental cues predictive of food availability elicits hypothalamic,pituitary,adrenal axis activation and increases operant responding for food in female rats

ADDICTION BIOLOGY, Issue 4 2009
Carlo Cifani
ABSTRACT The present study was undertaken to develop an animal model exploiting food cue-induced increased motivation to obtain food under operant self-administration conditions. To demonstrate the predictive validity of the model, rimonabant, fluoxetine, sibutramine and topiramate, administered 1 hour before the experiment, were tested. For 5 days, female Wistar rats were trained to self-administer standard 45 mg food pellets in one daily session (30 minutes) under FR1 (fixed ratio 1) schedule of reinforcement. Rats were then trained to an FR3 schedule and finally divided into two groups. The first group (control) was subjected to a standard 30 minutes FR3 food self-administration session. The second group was exposed to five presentations of levers and light for 10 seconds each (every 3 minutes in 15 minutes total). At the completion of this pre-session phase, a normal 30-minute session (as in the control group) started. Results showed that pre-exposure to environmental stimuli associated to food deliveries increased response for food when the session started. Corticosterone and adrenocorticotropic hormone plasma levels, measured after the 15-minute pre-exposure, were also significantly increased. No changes were observed for the other measured hormones (growth hormone, prolactin, thyroid-stimulating hormone, luteinizing hormone, insulin, amylin, gastric inhibitor polypeptide, ghrelin, leptin, peptide YY and pancreatic polypeptide). Rimonabant, sibutramine and fluoxetine significantly reduced food intake in both animals pre-exposed and in those not pre-exposed to food-associated cues. Topiramate selectively reduced feeding only in pre-exposed rats. The present study describes the development of a new animal model to investigate cue-induced increased motivation to obtain food. This model shows face and predictive validity, thus, supporting its usefulness in the investigation of new potential treatments of binge-related eating disorders. In addition, the present findings confirm that topiramate may represent an important pharmacotherapeutic approach to binge-related eating. [source]

Peptide YY3-36 and pancreatic polypeptide suppress food intake

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2006
Akihiro Asakawa
[source]

Spontaneous pancreatic islet amyloidosis in 40 baboons

JOURNAL OF MEDICAL PRIMATOLOGY, Issue 2 2002
G.B. Hubbard
Spontaneous amyloidosis occurs in many nonhuman primate species but remains difficult to diagnose and treat. Nonhuman primates continue to offer promise as animal models in which to study amyloidosis in humans. Amyloidosis was not diagnosed clinically but was found histologically in four male and 36 female baboons. The baboons averaged 18 years of age at death (range, 7,28 years). Clinical signs, if present, were hyperglycemia and cachexia. Blood glucose values were elevated in 12 of 30 baboons with available clinical pathology data. Four baboons had been clinically diagnosed as diabetic and three were treated with insulin. Amyloid was found in the islets of Langerhans of the pancreas in 40 baboons; 35 baboons had amyloid only in the islets of Langerhans. Amyloid was found in nonislet tissue of baboons as follows: five, nonislet pancreas; four, intestine and adrenal; three, kidney; two, prostate and spleen; and one each, lymph node, liver, gall bladder, stomach, tongue, urinary bladder, and salivary gland. Sections of paraffin-embedded tissues were evaluated for amyloid with hematoxylin and eosin (HE) and congo red (CR) staining, and using immunohistochemistry for human islet amyloid polypeptide (IAPP), calcitonin gene-related peptide (CGRP), glucagon, pancreatic polypeptide (PP), somatostatin (SS), and porcine insulin. Islet amyloid was positive with HE in 40 baboons, with CR in 39 baboons, and with IAPP and CGRP in 35 baboons. IAPP and CGRP only stained islet amyloid. PP, SS, glucagon, and porcine insulin did not stain amyloid. Islet amyloidosis in the baboon appears to be difficult to diagnose clinically, age-related, and similar to islet amyloidosis in other species. The baboon may be a good model for the study of islet amyloidosis in humans. [source]

Effects of pramlintide, an amylin analogue, on gastric emptying in type 1 and 2 diabetes mellitus

NEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2002
A. VELLA
Pramlintide delays gastric emptying, possibly by a centrally mediated mechanism. Our aim was to determine whether the effects of pramlintide on gastric emptying differ in people with type 1 or type 2 diabetes who had no history of complications. Using a randomized, three-period, two-dose, crossover design, we studied the effects of 0, 30, or 60 ,g t.i.d. pramlintide subcutaneously for 5 days each in six type 1 and six type 2 diabetic subjects. Gastric emptying of solids was measured by 13C-Spirulina breath test. Plasma pancreatic polypeptide (HPP) response to the test meal was also measured. Relative to placebo [t 50% 91 ± 6 min (means ± SEM)], pramlintide equally delayed gastric emptying following 30 or 60 ,g t.i.d. (268 ± 37 min, 329 ± 49 min, respectively; P < 0.01]. Postprandial HPP levels were lower in response to 30 and 60 ,g pramlintide compared to placebo. There were no significant differences in the effects on gastric emptying or HPP levels between type 1 and type 2 diabetic subjects. Pramlintide delays gastric emptying in diabetes unassociated with clinically detected complications. Further studies are needed in diabetic patients with impaired gastric motor function. [source]

Amylin in pancreatic islets and pancreatic endocrine neoplasms

PATHOLOGY INTERNATIONAL, Issue 9 2003
Tatsuo Tomita
Amylin is a chief constituent of the amyloid present in insulinomas, and is colocalized in beta islet cells. By immunocytochemical staining, all four islet cells including insulin, glucagon, somatostatin (SRIF) and pancreatic polypeptide (PP) cells were positively stained for amylin. The strongly insulin-positive cells corresponded with the strongly amylin-positive cells, and glucagon cells appeared to be strongly positive for amylin, whereas SRIF and PP cells were weakly positive for amylin. Among 37 cases of pancreatic endocrine neoplasms, insulinomas were more stronger stained for amylin than other islet cell tumors; however, amylin staining was the same or weaker than insulin staining. Glucagonomas and PP-omas were weakly positive for amylin, whereas six of 11 gastrinomas were weakly positive for amylin. It is concluded that three orthoendocrine tumors including insulinomas, glucagonomas and PP-omas were all positive for amylin, whereas ectopic hormone secreting gastrinomas were positive for amylin in six of 11 cases (55%). This colocalization of amylin with insulin, glucagon and PP may support a structure,function relationship of amylin and pancreatic hormones. The lesser immunoreactive amylin in pancreatic endocrine neoplasms than in normal islet cells may contribute to autonomous hypersecretion of hormones by pancreatic endocrine neoplasms. [source]

Well-differentiated neuroendocrine carcinoma (malignant carcinoid) of the extrahepatic biliary tract: report of two cases and literature review

APMIS, Issue 8 2010
SALVATORE SQUILLACI
Squillaci S, Marchione R, Piccolomini M, Colombo F, Bucci F, Bruno M, Bisceglia M. Well-differentiated neuroendocrine carcinoma (malignant carcinoid) of the extrahepatic biliary tract: report of two cases and literature review. APMIS 2010; 118: 543,56. The objectives of this study were to evaluate the frequency of carcinoid tumors of the extrahepatic biliary ducts (EHBDs) and the pathologic progression and the role of surgery in the management of this disease. We describe two cases of malignant carcinoids of the EHBDs, which presented as common bile duct tumors in two adult male patients, aged 52 and 70 years, who were diagnosed histologically on surgical resection specimens. A comprehensive review of the literature has also been performed with a focus on survival data. Microscopically, the tumors presented herein were composed of relatively small rounded cells with a trabecular or nesting pattern. Both cases were diffusely immunopositive for chromogranin and synaptophysin, and one of them was also focally reactive with somatostatin and pancreatic polypeptide. There was no expression in any of these tumors of thyroid transcription factor-1 (TTF-1), gastrin, insulin, glucagon, vasoactive intestinal peptide (VIP) and prolactin. The tumor showed transmural invasion in both cases, with lymph node metastasis and subcapsular liver tissue infiltration in one. Both patients are alive with no evidence of disease 41 months and 59 months, respectively, after surgery. Despite being extremely uncommon, with only 70 cases reported to date, carcinoids should be included in the differential diagnosis of EHBD tumors. This study emphasizes the necessity of complete surgical resection as the gold standard treatment for these lesions, and the importance of a correct pathologic diagnosis for prognostic implications. [source]

Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries

BRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2004
Dolores Prieto
The distribution of neuropeptide Y (NPY)-immunorective nerves and the receptors involved in the effects of NPY upon electrical field stimulation (EFS)- and noradrenaline (NA)-elicited contractions were investigated in horse penile small arteries. NPY-immunoreactive nerves were widely distributed in the erectile tissues with a particularly high density around penile intracavernous small arteries. In small arteries isolated from the proximal part of the corpora cavernosa, NPY (30 nM) produced a variable modest enhancement of the contractions elicited by both EFS and NA. At the same concentration, the NPY Y1 receptor agonist, [Leu31, Pro34]NPY, markedly potentiated responses to EFS and NA, whereas the NPY Y2 receptor agonist, NPY(13,36), enhanced exogenous NA-induced contractions. In arteries precontracted with NA, NPY, peptide YY (PYY), [Leu31, Pro34]NPY and the NPY Y2 receptor agonists, N - acetyl[Leu28,31]NPY (24,36) and NPY(13,36), elicited concentration-dependent contractile responses. Human pancreatic polypeptide (hPP) evoked a biphasic response consisting of a relaxation followed by contraction. NPY(3,36), the compound 1229U91 (Ile-Glu-Pro-Dapa-Tyr-Arg-Leu-Arg-Tyr-NH2, cyclic(2,4,)diamide) and eventually NPY(13,36) relaxed penile small arteries. The selective NPY Y1 receptor antagonist BIBP3226 ((R)- N2 -(diphenacetyl)- N -[(4-hydroxyphenyl)methyl]D -arginineamide) (0.3 ,M) shifted to the right the concentration,response curves to both NPY and [Leu31, Pro34]NPY and inhibited the contractions induced by the highest concentrations of hPP but not the relaxations observed at lower doses. In the presence of the selective NPY Y2 receptor antagonist BIIE0246 ((S)- N2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b,e]azepin-11-y1]-1-piperazinyl]-2-oxoethyl]cyclo-pentyl- N -[2-[1,2-dihydro,3,5 (4H)-dioxo-1,2-diphenyl-3H -1,2, 4-triazol-4-yl]ethyl]-argininamide) (0.3 ,M), the Y2 receptor agonists NPY(13,36) and N - acetyl[Leu28,31]NPY (24,36) evoked potent slow relaxations in NA-precontracted arteries, under conditions of nitric oxide (NO) synthase blockade. Mechanical removal of the endothelium markedly enhanced contractions of NPY on NA-precontracted arteries, whereas blockade of the neuronal voltage-dependent Ca2+ channels did not alter NPY responses. These results demonstrate that NPY can elicit dual contractile/relaxing responses in penile small arteries through a heterogeneous population of postjunctional NPY receptors. Potentiation of the contractions evoked by NA involve both NPY Y1 and NPY Y2 receptors. An NO-independent relaxation probably mediated by an atypical endothelial NPY receptor is also shown and unmasked in the presence of selective antagonists of the NPY contractile receptors. British Journal of Pharmacology (2004) 143, 976,986. doi:10.1038/sj.bjp.0706005 [source]

The analysis of immunophenotype of gastrin-producing tumors of the pancreas and gastrointestinal tract

CANCER, Issue 9 2003
Larissa Gurevich M.D., Ph.D.
Abstract BACKGROUND Gastrinomas are located more frequently in the pancreas, which normally has no cells that can produce gastrin. They have a more aggressive course than other pancreatic endocrine tumors and extrapancreatic gastrinomas associated with multiple endocrine neoplasia Type 1 syndrome. The current study analyzed immunophenotypes of gastrinomas and compared them with other pancreatic endocrine tumors. METHODS Twenty-one formalin-fixed, paraffin-embedded specimens (15-tumors in the pancreas, 1 in the duodenum, 1 in the stomach, 1 in the liver, and 3 of unknown primary location) accompanied by Zollinger,Ellison syndrome and 17 other pancreatic endocrine tumor specimens were investigated. They were stained immunohistochemically for gastrin, chromogranin A, synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide, calcitonin, serotonin, chorionic gonadotropin, adrenocorticotropic hormone, carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin 19. RESULTS Gastrinomas coexpressed neuroendocrine and exocrine markers, including chromogranin A, synaptophysin, carcinoembryonic antigen, cytokeratin 19, and epithelial membrane antigen. Carcinoembryonic antigen was found in all 17 gastrinomas (100%), cytokeratin 19 was found in 15 of 17 (88.2%) gastrinomas, and epithelial membrane antigen was found in 16 of 18 (88.9 %) gastrinomas. Cytokeratin 19, epithelial membrane antigen, and carcinoembryonic antigen were not found to be present in the pancreatic endocrine tumors, but chromogranin A and synaptophysin were. Chorionic gonadotropin was found in 16 gastrinomas (100%), but only in 2 of 17 other pancreatic endocrine tumors (11.8 %). CONCLUSIONS Pancreatic gastrinomas were characterized by the coexpression of neuroendocrine markers, exocrine markers, and chorionic gonadotropin. Therefore, pancreatic gastrinomas made a special intermediate group of tumors, which phenotypically combined features of neuroendocrine and exocrine neoplasms. These findings suggested that sporadic pancreatic gastrinomas and other pancreatic endocrine tumors are different phenotypically and are possibly of different origin. Cancer 2003. © 2003 American Cancer Society. [source]

Investigation of de novo Totally Random Biosequences, Part I

CHEMISTRY & BIODIVERSITY, Issue 8 2006
A General Method for in vitro Selection of Folded Domains from a Random Polypeptide Library Displayed on Phage
Abstract This paper reports the initial phase of a research aimed at investigating the folding frequency within a large library of polypeptides generated with a totally random sequence by phage-display technique. Resistance to proteolytic digestion has been used as a first, rudimentary folding criterion. The present paper describes, in particular, the development of a phage-display vector which has a selectable N-terminal affinity tag so that, after controlled proteolysis, the tag is cleaved from the phage. This enables the positive selection of phages that carry proteolytically resistant proteins. To test this system, avian pancreatic polypeptide (APP), one of the smallest proteins with a known structure, was chosen as a model, and its gene was inserted in a plasmid that was then used for phage display. A sequence of three amino acids, corresponding to a substrate for thrombin, was introduced at different locations within the APP sequence without significantly modifying the tertiary structure, as determined by circular dichroism (CD) analysis. These sequences were then used to show that the target tripeptide sequence was protected against proteolysis by the overall folding of the chain. Thus, these results show that the method permits the discrimination between folded and unfolded protein domains displayed on phage. The application of this protocol to a large library of totally random polypeptide chains is discussed as a preliminary to successive work, dealing with the production of totally random polypeptide sequences. [source]