Pancreatic Pancreatic Polypeptide Research Articles

Dietary L-lysine supplementation altered the content of pancreatic polypeptide, enzymes involved in glutamine metabolism, and β-actin in rats.

This study investigated the effects of Lys supplementation on serum pancreatic polypeptide (PP), glutamine (Gln) levels and the expression of PP, Gln synthetase (GlnS), glutaminase (Gls) and β-actin in different tissues such as pancreas, skeletal muscle, liver and kidney in rats. Male Sprague-Dawley rats were fed diets containing 7% casein supplemented with either 0% (Control), 1%, 1.5%, 3% Lys or 3% Lys with 1.5% Arg for a week. All rats were necropsied for collection of blood and tissues. Expression of PP, GlnS, Gls, and β-actin in tissues were determined using Western blotting. The results showed that the rats fed 3% supplemental Lys had significantly lower body weight gain (BWG) and food intake than the ≤ 1.5% Lys groups (P < 0.05). Supplementation with ≥ 1% Lys increased serum PP level (P < 0.05), but had no significant effect on pancreatic PP abundance (P > 0.05). GlnS expression was significantly lowered in skeletal muscle by ≥ 1.5% supplemental Lys compared to the Control (P < 0.05). The expression of Gls in the kidney was increased by the addition of 1.5% Arg to 3% Lys diet (P < 0.05). Liver β-actin significantly increased with both Lys and Arg supplementation and muscle β-actin significantly decreased (P < 0.05) with ≥ 1.5% supplemental Lys. Kidney β-actin significantly increased with Arg supplementation vs 3% Lys alone (P < 0.05). These results showed that dietary supplementation with ≥ 1.5% Lys significantly suppressed GlnS expression in the skeletal muscle, which may contribute to the decreased serum Gln levels, and that increased serum PP by Lys may be due to suppressed catabolism rather than increased synthesis of PP. Lys-induced PP may play a role in reducing food intake and BWG.

Pancreatic PYY but not PPY expression is responsive to short-term nutritional state and the pancreas constitutes the major site of PYY mRNA expression in chickens

PP-fold peptides such as peptide YY (PYY) and pancreatic polypeptide (PPY) are known to play key roles in vertebrate energy homeostasis. Until recently, no gene sequence was available for avian PYY and therefore a gap in knowledge of regulation of its expression exists in avian species. Here we further evidence the mRNA sequence for chicken PYY and show that the pancreas is the major site of its mRNA expression, with a secondary peak of expression around the distal jejunum, in contrast to mammals where the large intestine is the major site of PYY expression. We also demonstrate that pancreatic PYY expression is responsive to short-term and long-term nutritional state, increasing within hours of feeding, in contrast to intestinal PYY which does not fluctuate to the same extent, and pancreatic PPY which appears to be primarily determined by long-term energy state. Both pancreatic PYY and PPY expression were found to exhibit ontogeny, being evenly distributed throughout the pancreas in young (2wk) chicks but having a decreasing splenic to duodenal gradient by adolescence (12wk).

Pancreatic polypeptide responses to isoglycemic oral and intravenous glucose in humans with and without intact vagal innervation

Abstract Secretion of pancreatic polypeptide (PP) from the pancreatic PP cells is controlled partly by vagal mechanisms. Release is stimulated by cephalic stimulation and enteral but not parenteral nutrients. Ambient glucose levels modulate circulating PP levels as hypoglycemia stimulates while hyperglycemia inhibits secretion. The glucose sensing mechanism has yet to be determined but may involve a vagal pathway. To investigate the role of enteral stimuli with or without intact vagal innervation, while controlling for the glucose excursion caused by the OGTT, we measured PP plasma levels by an in-house radioimmunoassay in truncally vagotomized (n=15) and control individuals ( n = 10). All participants were studied by a 50-g oral glucose tolerance test (OGTT) with or without dipeptidyl peptidase 4 (DPP-4) inhibition (DPP-4i) and a subsequent isoglycemic intravenous glucose infusion (IGII). We included measurements from the DPP-4i day to determine the potential effect of DPP-4-cleaved peptides on PP secretion. In both vagotomized and controls, oral glucose elicited PP secretion. In controls, but not in the vagotomized participants, intravenous glucose significantly inhibited PP secretion suggesting a vagal glucose sensing mechanism dependent on intact vagal innervation. DPP-4i did not alter PP secretion in either group.

Pancreatic polypeptide responses to isoglycemic oral and intravenous glucose in humans with and without intact vagal innervation

Secretion of pancreatic polypeptide (PP) from the pancreatic PP cells is controlled partly by vagal mechanisms. Release is stimulated by cephalic stimulation and enteral but not parenteral nutrients. Ambient glucose levels modulate circulating PP levels as hypoglycemia stimulates while hyperglycemia inhibits secretion. The glucose sensing mechanism has yet to be determined but may involve a vagal pathway. To investigate the role of enteral stimuli with or without intact vagal innervation, while controlling for the glucose excursion caused by the OGTT, we measured PP plasma levels by an in-house radioimmunoassay in truncally vagotomized (n=15) and control individuals (n=10). All participants were studied by a 50-g oral glucose tolerance test (OGTT) with or without dipeptidyl peptidase 4 (DPP-4) inhibition (DPP-4i) and a subsequent isoglycemic intravenous glucose infusion (IGII). We included measurements from the DPP-4i day to determine the potential effect of DPP-4-cleaved peptides on PP secretion. In both vagotomized and controls, oral glucose elicited PP secretion. In controls, but not in the vagotomized participants, intravenous glucose significantly inhibited PP secretion suggesting a vagal glucose sensing mechanism dependent on intact vagal innervation. DPP-4i did not alter PP secretion in either group.

Overexpression of Hepatic Pancreatic Polypeptide Receptors in Chronic Pancreatitis

Pancreatic polypeptide (PP) receptors have recently been demonstrated on liver microsomal membranes although the mechanisms of PP action on hepatocytes remain uncertain. The binding characteristics of these high affinity receptors under pathophysiologic conditions were studied in rats with oleic acid-induced chronic pancreatitis (CP), a state associated with diminished pancreatic PP content. Sixteen pancreatitic and 11 sham-operated control animals either were 16-h fasted or were given free access to food prior to organ removal. Competitive binding studies were performed by incubating hepatocyte microsomal preparation with125I-labeled PP (20–40 pM) and increasing concentrations of nonlabeled PP (1 × 10−10to 1 × 10−6M). After total and nonspecific binding was quantified by gamma counting, coefficients of dissociation (Kd) and maximal binding sites (Bmax) were determined by Scatchard analysis of specifically bound radioactivity. Binding data were normalized to membrane protein content and expressed as means ± standard error.Bmaxwas significantly greater in tissue from fed control animals than from fasted controls (4.46 ± 0.36 versus 2.83 ± 0.25,P< 0.05).Bmaxwas significantly greater under fasted conditions in tissue from CP animals than from controls (5.25 ± 0.94 versus 2.83 ± 0.25,P< 0.01). Under fed conditions, this difference was abolished by the increase in maximal binding in the control group. The fasting-associated decrease in maximal binding sites observed in controls did not occur in CP specimens. IncreasedBmaxin fed versus fasted control, as well as fasted CP versus fasted control, were associated with slight reciprocal decreases in receptor affinity. These data indicate that hepatic PP receptor concentration is upregulated in this model of chronic pancreatitis, most likely due to diminished exposure to ligand. Furthermore, normal PP receptor responses to the fed/fasted state are blunted in this condition. Regulatable PP receptor changes may play a role in altered hepatic metabolism previously observed in chronic pancreatitis.

Neuropeptide Y-related peptides from the pancreas of a teleostean (eel), holostean (bowfin) and elasmobranch (skate) fish

Homologous peptides belonging to the pancreatic polypeptide (PP) family were isolated from the pancreas of a teleostean fish, the American eel (Anguilla rostrata), an holostean fish, the bowfin (Amia calva) and an elasmobranch fish, the skate (Raja rhina), and their primary structures were determined. The peptides show stronger homology to neuropeptide Y, particularly in their COOH-terminal regions, than to peptide YY or pancreatic polypeptide and contain an alpha-amidated COOH-terminal tyrosine residue. The skate peptide Tyr-Pro-Pro-Lys-Pro-Glu-Asn-Pro-Gly-Asp10-Asp-Ala-Ala-Pro-Glu-Glu- Leu-Ala-Lys- Tyr20-Tyr-Ser-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu30-Ile-Thr-Arg- Gln-Arg-Tyr-NH2 represents the first member of the PP family to be isolated from a cartilaginous fish. The primary structure of the pancreatic PP family peptide has been more strongly conserved among the phylogenetically more ancient holostean and elasmobranch fishes than among the teleosts. A comparison of the primary structures of all PP family peptides supports the hypothesis and evolution has acted to conserve features of tertiiary structure in the molecules (e.g., the polyproline- and alpha-helices) rather than individual amino acid residues.

Modulatory effect of glucose, amino acids, and secretin on CCK-8-induced somatostatin and pancreatic polypeptide release in dogs.

Protein- and fat-rich test meals elicit a strong stimulatory effect on postprandial somatostatin (SLI) and pancreatic polypeptide (PP) release, whereas carbohydrate-rich meals rather attenuate the response of both hormones. Since there is evidence that intestinal hormones might contribute to the postprandial SLI and PP response, it was the aim of the present study to determine in dogs the effect of low-dose cholecystokinin octapeptide (CCK-8) on basal hormone levels and also during a background infusion of amino acids or glucose. In a group of six conscious dogs, sulfated CCK-8 was infused intravenously (i.v.) via a hindleg vein at stepwise increasing infusion rates of 10, 30, and 50 pmol X kg-1 X h. The infusion of CCK was applied during a background infusion of saline (2 ml/min), glucose (0.2 g/min), or an amino acid mixture (8.5%, 2 ml/min). CCK-8 had no effect on plasma insulin and glucagon levels under all experimental conditions. Plasma SLI levels were significantly stimulated by all doses of CCK. This stimulatory effect was similar during background infusions of either saline, glucose, or amino acids, respectively. Pancreatic polypeptide (PP) levels rose 200-300 pg/ml during CCK plus saline. This was slightly attenuated by glucose. During CCK plus amino acids, the PP response was augmented to 600-800 pg/ml. Since secretin is also released after the ingestion of a meal and intraduodenal acidification is a potent stimulus not only of secretin but also of gastric and pancreatic SLI release, the effect of secretin was examined additionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired pancreatic polypeptide response to insulin hypoglycemia in obese subjects.

We have studied the effect of insulin hypoglycemia on the secretion of pancreatic polypeptide (PP) in 14 obese subjects with normal glucose tolerance and in 6 normal controls. Infusion of insulin 0.1 U/kg/h in controls and 0.12 U/kg/h in the obese, for one hour, produced a progressive hypoglycemia, similar in both groups (nadir 2 mmol/l at 50 min). The secretion of PP was less in obese subjects than in controls (peak 116 mmol/l vs 184 pmol/l, P less than 0.01) (integrated secretion sigma delta PP 288 vs 472 pmol/l, P less than 0.01) and was also delayed in the obese subjects beginning at 50 min instead of 40 min. The secretion of glucagon and of C-peptide were not different in the two groups, but the integrated response of ACTH was higher in the obese (sigma delta ACTH 52 pmol/l vs 25 pmol/l, P less than 0.01). The secretory response of growth hormone (STH) was smaller in the obese group (peak 8.6 +/- 1.28 vs 21.4 +/- 6.4 ng/ml, P less than 0.01). The reduced secretion of PP in obese subjects could be due to impaired sensitivity to hypoglycemia of the central control mechanism for PP release. The similarity of the reductions in the secretion of both PP and STH support this hypothesis, although a reduction in the secretory capacity of pancreatic PP cells cannot be excluded.

Update on pancreatic polypeptide as a specific marker for endocrine tumours of the pancreas and gut.

Serum levels of pancreatic polypeptide (PP) were determined in 31 patients with endocrine tumours, localized in the pancreas (n = 16), small intestine (n = 13) and respiratory tract (n = 2). Two further patients with laxative abuse were investigated. Elevated serum levels in the peripheral circulation were noted in 56% of the patients with pancreatic tumours, in 60% of those with gut or bronchial tumours and in both patients with laxative abuse. Our study suggests that the elevated PP concentrations found in connection with endocrine gastrointestinal tumours originate from non-tumour pancreatic PP cells and only occasionally from the tumour. PP is a valuable tumour marker for endocrine gastrointestinal tumours, although it is not specific for pancreatic tumours. Certain inflammatory diseases, renal function and consumption of laxatives must be considered when evaluating elevated PP levels. Serum PP seems to be of limited value for evaluating the response to cytotoxic therapy.