Plasma Pancreatic Polypeptide Research Articles

High Fat Diets Increase Plasma Cholecystokinin and Pancreatic Polypeptide, and Decrease Plasma Insulin and Feed Intake in Lactating Cows

High fat diets often decrease feed intake in dairy cows; however, mechanisms underlying fat-induced depression of feed intake are yet to be established. The postulate that high fat diets decrease feed intake by increasing concentrations of lipid metabolites or satiety hormones in blood was tested by using eight multiparous Holstein cows in a simultaneously replicated 4 × 4 Latin-square design. Treatments were control diet with 1) no fat added, 2) 30 g/kg calcium salts of long-chain fatty acids, 3) 60 g/kg calcium salts of long-chain fatty acids, and 4) 90 g/kg calcium salts of long-chain fatty acids. Cows were fed once daily a diet of concentrate, corn silage, alfalfa haylage and alfalfa hay (50:25:14:11 on a dry matter basis). Dry matter and energy intakes were decreased by inclusion of calcium salts of long-chain fatty acids >30 g/kg of total diet dry matter (P = 0.0001). Plasma nonesterified fatty acids and triglyceride concentrations were increased linearly by feeding increasing amounts of fat (P < 0.003 and P = 0.0001, respectively), whereas plasma β-hydroxybutyrate and glucose concentrations were not influenced by supplemental fat. Fat supplementation increased postfeeding plasma cholecystokinin concentrations and linearly increased plasma pancreatic polypeptide concentrations. Highest concentrations of plasma cholecystokinin (P < 0.001) and pancreatic polypeptide (P < 0.05) were observed in cows fed the 90 g/kg fat supplement. Plasma insulin was lowered linearly by feeding fat (P = 0.0001). Increased concentrations of cholecystokinin and pancreatic polypeptide were associated with decreased intakes of feed and energy, whereas insulin may not be involved in the control of feed intake in cows fed fat.

118 Functional Properties of Bifidobacterium Animalis Subsp. Lactis Cect 8145 in Canine Nutrition

Abstract The gut bacterial population has been demonstrated to influence the physiologic and metabolic functions of the host by modulating energy expenditure and immune response, therefore contributing to the health of the host. However, there is little information regarding the effects of probiotics and postbiotics on canine nutrition. The objective of this study was to evaluate the longitudinal effects of daily supplementation of Bifidobacterium animalis subsp. lactis CECT 8145 and the same strain in a heat-killed presentation (postbiotic) on weight management, fecal fermentative end-product concentration, gut hormones, postprandial glycemic and insulinemic response in overweight dogs. Thirty-six adult dogs were used in a completely randomized, double-blinded, placebo-controlled study, with 12 animals per treatment. Dogs were fed a commercial dry extruded complete and balanced diet twice daily to maintain body weight. Following a 60 d adaptation to the control diet, dogs were fed their respective treatment diets for 90 d. Treatments were provided by ADM Biopolis (Valencia, Spain) and given via gelatin capsules before morning feeding to ensure consumption of the total dose of their placebo, probiotic, or heat-killed probiotic. The treatments supplementation had no detrimental effect on the overall dog's health. Throughout the experimental period, fecal scores did not differ among dogs fed different dietary treatments (P &amp;gt; 0.05). However, fecal pH was significantly lower (P = 0.0049) in the dogs fed the postbiotic (5.8) compared with the group control (6.1). Greater fecal concentration of propionate (P=0.0427) was observed on dogs fed the probiotic and the dogs fed the postbiotic compared with the group control. Pancreatic polypeptide plasma concentration was less (P &amp;lt; 0.05) in the dogs fed the probiotic compared with treatment control. These data suggest that the longitudinal supplementation of this specific strain in the live and heat-killed presentation may interact with gut microbial fermentation and gut hormonal regulation.

High Coexpression of the Ghrelin and LEAP2 Receptor GHSR With Pancreatic Polypeptide in Mouse and Human Islets.

Islets represent an important site of direct action of the hormone ghrelin, with expression of the ghrelin receptor (growth hormone secretagogue receptor; GHSR) having been localized variably to alpha cells, beta cells, and/or somatostatin (SST)-secreting delta cells. To our knowledge, GHSR expression by pancreatic polypeptide (PP)-expressing gamma cells has not been specifically investigated. Here, histochemical analyses of Ghsr-IRES-Cre × Cre-dependent ROSA26-yellow fluorescent protein (YFP) reporter mice showed 85% of GHSR-expressing islet cells coexpress PP, 50% coexpress SST, and 47% coexpress PP + SST. Analysis of single-cell transcriptomic data from mouse pancreas revealed 95% of Ghsr-expressing cells coexpress Ppy, 100% coexpress Sst, and 95% coexpress Ppy + Sst. This expression was restricted to gamma-cell and delta-cell clusters. Analysis of several single-cell human pancreatic transcriptome data sets revealed 59% of GHSR-expressing cells coexpress PPY, 95% coexpress SST, and 57% coexpress PPY + SST. This expression was prominent in delta-cell and beta-cell clusters, also occurring in other clusters including gamma cells and alpha cells. GHSR expression levels were upregulated by type 2 diabetes mellitus in beta cells. In mice, plasma PP positively correlated with fat mass and with plasma levels of the endogenous GHSR antagonist/inverse agonist LEAP2. Plasma PP also elevated on LEAP2 and synthetic GHSR antagonist administration. These data suggest that in addition to delta cells, beta cells, and alpha cells, PP-expressing pancreatic cells likely represent important direct targets for LEAP2 and/or ghrelin both in mice and humans.

Auricular vagal nerve stimulation enhances gastrointestinal motility and improves interstitial cells of Cajal in rats treated with loperamide.

Gastrointestinal (GI) motility disorders affect a large proportion of the population with limited treatment options. The aims of this study were to investigate the potential of a non-invasive method of auricular vagal nerve stimulation (aVNS) for treating GI dysmotility and to explore possible mechanisms involving slow waves and interstitial cells of Cajal (ICC). Normal rats were treated daily with loperamide for 1 week and then treated, while still on daily loperamide, with aVNS/Sham-aVNS for another 1week. Gastric emptying (GE), small intestine transit (SIT), and GI slow waves were measured. The plasma level of pancreatic polypeptide (PP) and noradrenaline (NE) was assessed by ELISA. ICC in the gastric antrum were detected by immunohistochemistry. (a) aVNS significantly increased the percentage of normal GI slow waves (p<0.05 for both fasting and postprandial states, vs. Sham-aVNS) and accelerated GE (p<0.05, vs. Sham-aVNS) and SIT (p<0.05, vs. Sham-aVNS) impaired by loperamide. (b) aVNS increased plasma PP (p<0.01) and decreased plasma NE (p<0.01), compared with Sham-aVNS. (c) Gastric ICC was decreased by loperamide (p<0.01) but increased after aVNS (p<0.01, vs. Sham aVNS). Loperamide induces upper GI dysmotility. aVNS accelerates upper GI transit and improving pace-making activity mediated via the ICC. Non-invasive aVNS may have a therapeutic potential for upper GI dysmotility.

Acute pancreatitis-induced islet dysfunction in ferrets

Background/Objectives: The pathogenesis of hyperglycemia during acute pancreatitis (AP) remains unknown due to inaccessibility of human tissues and lack of animal models. We aimed to develop an animal model to study the mechanisms of hyperglycemia and impaired glucose tolerance in AP. MethodsWe injected ferrets with intraperitoneal cerulein (50 μg/kg, 9 hourly injections) or saline. Blood samples were collected for glucose (0, 4, 8, 12, 24h); TNF-α, IL-6 (6h); amylase, lipase, insulin, glucagon, pancreatic polypeptide (PP), glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) (24h). Animals underwent oral glucose tolerance test (OGTT), mixed meal tolerance test (MMTT) at 24h or 3 months, followed by harvesting pancreas for histopathology and immunostaining. ResultsCerulein-injected ferrets exhibited mild pancreatic edema, neutrophil infiltration, and elevations in serum amylase, lipase, TNF-α, IL-6, consistent with AP. Plasma glucose was significantly higher in ferrets with AP at all time points. Plasma glucagon, GLP-1 and PP were significantly higher in cerulein-injected animals, while plasma insulin was significantly lower compared to controls. OGTT and MMTT showed abnormal glycemic responses with higher area under the curve. The hypoglycemic response to insulin injection was completely lost, suggestive of insulin resistance. OGTT showed low plasma insulin; MMTT confirmed low insulin and GIP; abnormal OGTT and MMTT responses returned to normal 3 months after cerulein injection. ConclusionsAcute cerulein injection causes mild acute pancreatitis in ferrets and hyperglycemia related to transient islet cell dysfunction and insulin resistance. The ferret cerulein model may contribute to the understanding of hyperglycemia in acute pancreatitis.

Effect of Acute Sprint Exercise on Myokines and Food Intake Hormones in Young Healthy Men.

Physical exercise is known to influence hormonal mediators of appetite, but the effect of short-term maximal intensity exercise on plasma levels of appetite hormones and cytokines has been little studied. We investigated the effect of a 30 s Wingate Test, followed by a postprandial period, on appetite sensations, food intake, and appetite hormones. Twenty-six physically active young males rated their subjective feelings of hunger, prospective food consumption, and fatigue on visual analogue scales at baseline, after exercise was completed, and during the postprandial period. Blood samples were obtained for the measurement of nesfatin-1, ghrelin, leptin, insulin, pancreatic polypeptide (PP), human growth factor (hGH) and cytokine interleukin-6 (IL-6), irisin and plasma lactate concentrations, at 30 min before exercise, immediately (210 s) after exercise, and 30 min following a meal and at corresponding times in control sedentary males without ad libitum meal intake, respectively. Appetite perceptions and food intake were decreased in response to exercise. Plasma levels of irisin, IL-6, lactate, nesfatin-1 and ghrelin was increased after exercise and then it was returned to postprandial/control period in both groups. A significant rise in plasma insulin, hGH and PP levels after exercise was observed while meal intake potentiated this response. In conclusion, an acute short-term fatiguing exercise can transiently suppress hunger sensations and food intake in humans. We postulate that this physiological response involves exercise-induced alterations in plasma hormones and the release of myokines such as irisin and IL-6, and supports the notion of existence of the skeletal muscle–brain–gut axis. Nevertheless, the detailed relationship between acute exercise releasing myokines, appetite sensations and impairment of this axis leading to several diseases should be further examined.

GPR120 Regulates Pancreatic Polypeptide Secretion From Male Mouse Islets via PLC-Mediated Calcium Mobilization.

The free fatty acid receptor G protein-coupled receptor 120 (GPR120) is expressed in pancreatic islets, but its specific cell distribution and function have not been fully established. In this study, a GPR120-IRES-EGFP knockin (KI) mouse was generated to identify GPR120-expressing cells with enhanced green fluorescence proteins (EGFP). EGFP-positive cells collected from KI mouse islets by flow cytometry had a significantly higher expression of pancreatic polypeptide (PP) evidenced by reverse transcriptase (RT)-quantitative polymerase chain reaction (qPCR). Single-cell RT-PCR and immunocytochemical double staining also demonstrated the coexpression of GPR120 with PP in mouse islets. The GPR120-specific agonist TUG-891 significantly increased plasma PP levels in mice. TUG-891 significantly increased PP levels in islet medium in vitro, which was markedly attenuated by GPR120 small interfering RNA treatment. TUG-891-stimulated PP secretion in islets was fully blocked by pretreatment with YM-254890 (a Gq protein inhibitor), U73122 (a phospholipase C inhibitor), or thapsigargin (an inducer of endoplasmic reticulum Ca2+ depletion), respectively. TUG-891 triggered the increase in intracellular free Ca2+ concentrations ([Ca2+]i) in PP cells, which was also eliminated by YM-254890, U73122, or thapsigargin. GPR120 gene expression was significantly reduced in islets of high-fat diet (HFD)-induced obese mice. TUG-891-stimulated PP secretion was also significantly diminished in vivo and in vitro in HFD-induced obese mice compared with that in normal-chow diet control mice. In summary, this study demonstrated that GPR120 is expressed in mouse islet PP cells and GPR120 activation stimulated PP secretion via the Gq/PLC-Ca2+ signaling pathway in normal-chow diet mice but with diminished effects in HFD-induced obese mice.

254-LB: Characterization of Ghrelin Receptor Expression in Mouse Islets Reveals Pancreatic Polypeptide Cells as a Key Ghrelin Target

Objective: While expression of the ghrelin receptor, GHSR (growth hormone secretagogue receptor), by pancreatic islets has been investigated, data regarding the specific islet cell types that express GHSR are inconsistent and incomplete. For instance, transcriptomic studies indicate marked GHSR expression by somatostatin (SST)-secreting delta cells vs. little to no GHSR expression by alpha cells and beta cells, which contrasts studies suggesting direct actions of ghrelin on GHSRs expressed by alpha cells and beta cells. Also, to our knowledge, GHSR expression by pancreatic polypeptide (PP) cells has not previously been directly investigated. The aims of this study were to determine GHSR expression within the four principal islet endocrine cell types and the effects of ghrelin on circulating PP. Methods: Ghsr-IRES-Cre mice, which express Cre recombinase directed by the GHSR promoter, crossed to Cre-dependent ROSA26-YFP reporter mice were used to histologically identify GHSR expression in islets. Double and triple labeling for YFP-immunoreactivity (IR) with insulin-IR, glucagon-IR, SST-IR, and/or PP-IR was performed to determine GHSR co-expression with islet hormones. Pharmacological manipulations were used to examine in vivo effects of acyl-ghrelin on plasma PP. Results: Eighty-five % of YFP-IR cells expressed PP-IR, 50% expressed SST-IR, and none expressed insulin-IR or glucagon-IR. GHSR antagonist raised plasma PP in overnight-fasted C57BL/6N mice. However, acyl-ghrelin administration had no effect on plasma PP in C57BL/6N mice. Conclusions: These results suggest that within mouse pancreatic islets, GHSR expression occurs most abundantly in PP cells and that pharmacologic blockade of ghrelin action raises plasma PP. Disclosure D. Gupta: None. B.K. Mani: None. K. Shankar: None. S. Osborne-Lawrence: None. N. Metzger: None. J.M. Zigman: Stock/Shareholder; Self; Medtronic. Funding Diana and Richard C. Strauss Professorship in Biomedical Research; Mr. and Mrs. Bruce G. Brookshire Professorship in Medicine; Kent and Jodi Foster Distinguished Chair in Endocrinology; University of Texas Southwestern Medical Center (to J.M.Z.)

Dairy products influence gut hormone secretion and appetite differently: A randomized controlled crossover trial

Little is known about how dairy products with different nutrient contents and food matrices affect appetite sensation and gut hormone secretion. The objective of this study was to investigate how appetite sensation and gut hormone secretion in healthy adults are affected by meals with the same amount of fat but from different dairy products. Forty-seven healthy adults (70% women) were recruited to a randomized controlled crossover study with 4 dairy meals consisting of butter, cheese, whipped cream, or sour cream, corresponding to 45 g (approximately 60 energy percent) of fat. Plasma samples were collected for analysis of cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY), and ghrelin concentrations at 0, 2, 4, and 6 h after the meals and analyzed as the incremental area under the curve (iAUC0-6h) in a mixed model. Hunger, satiety, and appetite sensations were measured with a visual analog scale (VAS) immediately after finishing the meals and at 4 and 6 h postprandially. Intake of cheese induced a higher level of plasma PP-iAUC0-6h compared with butter or whipped cream, and a higher level of plasma CCK-iAUC0-6h compared with whipped cream. Intake of whipped cream increased VAS appetite at 4 h compared with cheese or sour cream, and at 6 h compared with cheese or butter. No significant meal effect was found for hunger, satiety, plasma PYY, or plasma ghrelin concentration. Intake of cheese increased postprandial plasma PP and CCK concentrations and decreased appetite compared with whipped cream but not with sour cream. These findings encourage further investigations of how different dairy products affect gut hormone secretion and appetite sensation.

In vivo positron emission tomography imaging of decreased parasympathetic innervation in the gut of vagotomized patients.

Parasympathetic neuropathy is a key feature in many common disorders, including diabetes, neurological disorders, and cancers, but few objective methods exist for assessing damage to the parasympathetic nervous system, particularly in the gastrointestinal system. This study aimed to validate the use of 11 C-donepezil positron emission tomography (PET) to assess parasympathetic integrity in a group of vagotomized patients. Sixteen healthy controls and 12 patients, vagotomized due to esophagectomy, underwent 11 C-donepezil PET, measurement of colonic transit time, quantification of plasma pancreatic polypeptide (PP), and assessment of subjective long-term symptoms. Vagotomized patients had significantly decreased PET signal in the small intestine and colon compared with healthy controls (5.7 [4.4-7.9] vs 7.4 [4.5-11.3], P=.01 and 1.4 [1.1-2.1] vs 1.6 [1.4-2.4], P<.01, respectively). Vagotomized patients also displayed a significantly increased colonic transit time (2.9±0.9h vs 1.9±0.8h), P<.01 and increased volumes of the small intestine and colon (715ccm [544-1177] vs 443ccm [307-613], P<.01 and 971ccm [713-1389] vs 711ccm [486-1394], P=.01, respectively). Patients and controls did not differ in PP ratio levels after sham feeding, but PP ratio at 10minutes. after sham feeding and PET signal intensity in the small intestine was positively correlated (P=.03). We found significantly decreased 11 C-donepezil signal in the intestine of vagotomized patients, supporting that 11 C-donepezil PET is a valid measure of intestinal parasympathetic denervation.

Glucose-Dependent Insulinotropic Polypeptide Is a Pancreatic Polypeptide Secretagogue in Humans.

Glucose-dependent insulinotropic polypeptide (GIP) has been suggested to stimulate the secretion of pancreatic polypeptide (PP), an islet hormone thought to regulate gut motility, appetite, and glycemia. To determine whether human GIP1-42 (hGIP) stimulates PP secretion. As glycemia modulates the secretion of PP, we measured plasma PP concentrations from 2 studies in healthy men (n = 10) and in patients with type 2 diabetes (T2D) (n = 12), where hGIP1-42 had been administered intravenously during fasting glycemia, hyperglycemia (12 mmol/L), and insulin-induced hypoglycemia (targets: 2.5 mmol/L [healthy]; 3.5 mmol/L [T2D]). Porcine GIP1-42 (pGIP) was also infused intra-arterially in isolated porcine pancreata (n = 4). Mean fasting plasma glucose concentrations were approximately 5 mmol/L (healthy) and approximately 8 mmol/L (T2D). At fasting glycemia, PP concentrations were higher during intravenous hGIP1-42 infusion compared with saline in healthy men (mean [standard error of the mean, SEM], net incremental areas under the curves (iAUCs)[0-30min], 403 [116] vs -6 [57] pmol/L × min; P = 0.004) and in patients with T2D (905 [177] vs -96 [86] pmol/L × min; P = 0.009). During hyperglycemic clamping, mean [SEM] PP concentrations were significantly higher during hGIP1-42 infusion compared with saline in patients with T2D (771 [160] vs -183 [117] pmol/L × min; P = 0.001), but not in healthy individuals (-8 [86] vs -57 [53] pmol/L × min; P = 0.69). When plasma glucose levels were declining in response to exogenous insulin, mean [SEM] PP concentrations were higher during hGIP1-42 infusion compared with saline in healthy individuals (294 [88] vs -82 [53] pmol/L × min; P = 0.0025), but not significantly higher in patients with T2D (586 [314] vs -120 [53]; P = 0.070). At target hypoglycemia, PP levels surged in both groups during both hGIP1-42 and saline infusions. In isolated pancreata, pGIP1-42 increased mean [SEM] PP output in the pancreatic venous effluent (baseline vs infusion, 24[5] vs 79 [16] pmol/min x min; P = 0.044). GIP1-42 increases plasma PP secretion in healthy individuals, patients with T2D, and isolated porcine pancreata. Hyperglycemia blunts the stimulatory effect of hGIP1-42 in healthy individuals, but not in patients with T2D.

Utility of the plasma pancreatic polypeptide response to modified sham feeding in diabetic gastroenteropathy and non-ulcer dyspepsia.

The relationship between cardiovascular and gastrointestinal (ie, plasma pancreatic polypeptide [PP] response to modified sham feeding [MSF]) indices of vagal function is unclear. Hyperglycemia inhibits PP secretion via vagally mediated mechanisms. Our aims were to (a) compare the PP response, (b) its relationship with glycemia, and (c) the relationship between PP response to MSF, gastric emptying (GE) of solids, and symptoms during GE study in healthy controls, patients with diabetic gastroenteropathy (DM), and non-ulcer dyspepsia (NUD). In 24 healthy controls, 40 DM, and 40 NUD patients, we measured plasma PP concentrations during MSF, cardiovagal functions, GE, and symptoms during a GE study. Baseline PP concentrations were higher in DM than in controls and NUD (P=.01), and in type 2 than in type 1 DM patients (P<.01). The PP increment during MSF was normal (≥20pg/mL) in 70% of controls, 54% of DM, and 47% of NUD patients. Overall, the PP response and cardiovagal tests were concordant (P=.01). Among patients with a reduced PP increment with MSF, 7/10 of T1DM and 1/7 of T2DM patients had moderate or severe cardiovagal dysfunctions (P<.05). The PP response to MSF was not associated with GE. Up to 30% of healthy controls have a reduced PP increment during MSF, limiting the utility of this test to detect vagal injury. The PP response is more useful when it is normal than abnormal. A reduced PP response is more likely to be associated with cardiovagal dysfunctions in T1DM than in T2DM.

Acipimox Administration With Exercise Induces a Co-feedback Action of the GH, PP, and PYY on Ghrelin Associated With a Reduction of Peripheral Lipolysis in Bulimic and Healthy-Weight Czech Women: A Randomized Study.

Objective: Anti-lipolytic drugs and exercise are enhancers of growth hormone (GH) secretion. Decreased circulating free fatty acids (FFA) have been proposed to exert ghrelin-GH feedback loop after administration of an anti-lipolytic longer-acting analog of nicotinic acid, Acipimox (OLB, 5-Methylpyrazine-2-carboxylic acid 4-oxide, molecular weight of 154.1 Da). OLB administration strongly suppresses plasma FFA during exercise. Neuroendocrine perturbations of the adipose tissue (AT), gut, and brain peptides may be involved in the etiopathogenesis of eating disorders including bulimia nervosa (BN) and anorexia nervosa. BN is characterized by binge eating, self-induced vomiting or excessive exercise.Approach: To test the hypothesis that treatment with OLB together with exercise vs. exercise alone would induce feedback action of GH, pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), and leptin on ghrelin in Czech women with BN and in healthy-weight Czech women (HW). The lipolysis rate (as glycerol release) in subcutaneous abdominal AT was assessed with microdialysis. At an academic medical center, 12 BN and 12 HW (the control group) were randomized to OLB 500 mg 1 h before a single exercise bout (45 min, 2 W/kg of lean body mass [LBM]) once a week vs. identical placebo over a total of 2 weeks. Blood plasma concentrations of GH, PP, PYY, leptin, ghrelin, FFA, glycerol, and concentrations of AT interstitial glycerol were estimated during the test by RIA utilizing 125I-labeled tracer, the electrochemiluminescence technique (ECLIA) or colorimetric kits.Results: OLB administration together with short-term exercise significantly increased plasma GH (P < 0.0001), PP (P < 0.0001), PYY, and leptin concentrations and significantly decreased plasma ghrelin (P < 0.01) concentrations in both groups, whereas short-term exercise with placebo resulted in plasma ghrelin (P < 0.05) decrease exclusively in BN. OLB administration together with short-term exercise significantly lowered local subcutaneous abdominal AT interstitial glycerol (P < 0.0001) to a greater extent in BN.Conclusion: OLB-induced suppression of plasma ghrelin concentrations together with short-term exercise and after the post-exercise recovering phase suggests a potential negative co-feedback of GH, PP, PYY, and leptin on ghrelin secretion to a greater extent in BN. Simultaneously, the exercise-induced elevation in AT interstitial glycerol leading to a higher inhibition of peripheral lipolysis by OLB in BN.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03338387

Development of small intestinal enzyme activities and their relationship with some gut regulatory peptides in grazing sheep

Growth depends on an animal's capacity to digest and assimilate ingested nutrients, and insufficient supply and impairment will constrain lamb growth. Eight groups of Alpine Finewool lambs were harvested on 0, 3, 7, 14, 21, 28, 42, and 56 d to measure pH and enzymatic activities in the duodenum, proximal jejunum, middle jejunum, distal jejunum, and ileum mucosa or digesta. From the duodenum to the ileum the pH of intestinal mucosa and digesta increased, whereas pH changed very little with age. The trypsin, chymotrypsin, lipase, lactase, and α-amylase activities observed at birth decreased by d 3, followed by a nonuniform enzymatic response in the small intestine. The trypsin activity increased from d 3 to peak, at d 21, followed by a decline. Chymotrypsin activity followed the same general trend but with smaller responses in activities. Trypsin demonstrated greater enzymatic activity than chymotrypsin at the same age. The lipase activity of small intestinal mucosa and digesta changed little with age. The lactase activity was high at birth, decreased by d 3, and then increased, followed by a decrease as lambs approached weaning. α-Amylase activity was similar in the small intestinal mucosa and digesta at birth but increased with age for the duodenum and proximal jejunum. Plasma concentrations of cholecystokinin (CCK), secretin, and gastrin were positively correlated ( < 0.05) with ileal mucosa lipase activity. Plasma concentration of CCK, secretin, gastrin, and gastric inhibitory polypeptide (GIP) were positively correlated ( < 0.05) with ileal mucosa lactase activity. Plasma concentration of pancreatic polypeptide (PP) was negatively correlated ( < 0.05) with lactase activity in the middle jejunum and ileal mucosa. Plasma concentrations of CCK, secretin, gastrin, and GIP were positively correlated ( < 0.05) with α-amylase activity in the ileal mucosa but negatively correlated ( < 0.05) with duodenum, prejejunum, and middle jejunum. Plasma PP concentrations were positively correlated ( < 0.01) with α-amylase activity of duodenum, middle jejunum, and postjejunum mucosa but not with the enzyme activity of postjejunum and ileal mucosa ( > 0.05). Small intestinal enzymatic activities exist and may be sufficient to enhance lamb growth via appropriate nutrient supplementation.

Effect of heat exposure and exercise on food intake regulation: A randomized crossover study in young healthy men

ObjectiveThe effect of physical activity on food intake regulation may be moderated by environmental temperature. The aim of the study was to determine the single and combined effects of metabolic activity and temperature on energy intake and its hormonal regulation. MethodsA randomized crossover study was conducted in the laboratory. Ten healthy and physically active young Afro-Caribbean men participated in four experimental sessions (rest at 22°C and 31°C and cycling at 60% of their maximal oxygen uptake at 22°C and 31°C, all for 40 min). Each test period was followed by a 30-min recovery period and then an ad libitum meal. The main outcome measures were energy balance, subjective appetite, and plasma pancreatic polypeptide (PP), cholecystokinin (CCK) and ghrelin concentrations. ResultsRelative energy intake was significantly decreased whereas plasma PP was increased in the exercise conditions (p=0.004 and p=0.002, respectively). Postprandial levels of CCK were elevated only in the rest conditions. Exposure to heat induced a decrease in plasma ghrelin (p=0.031). ConclusionsExercise induced a short-term energy deficit. However, modifications in the hormonal regulation of food intake in response to short-term heat or heat and exercise exposure seem to be minor and did not induce changes in energy intake.This trial was registered at clinicaltrials.gov as NCT02157233.

Gastrointestinal hormones and their role in obesity.

Pandemic obesity is the most pressing health issue of this century. The most successful treatment so far is bariatric surgery, but for various reasons, surgery cannot be applied to all patients who require treatment. Gastrointestinal hormones are likely to play a key role in the success of bariatric surgery. This article examines in detail three of these gut hormones: peptide YY, oxyntomodulin and pancreatic polypeptide, and reviews how recent developments may offer new targets for therapy. Both the free fatty acid 2 and the melanocortin 4 receptors have been discovered to regulate peptide YY and glucagon-like peptide-1 secretion, and drugs targeting these may represent new antiobesity therapies. Dual agonism of glucagon-like peptide-1 and glucagon receptors, for example with oxyntomodulin, has synergistic effects in reducing appetite and increasing energy expenditure. Plasma pancreatic polypeptide concentration correlates with visceral adiposity, and may serve as a biomarker for metabolic syndrome. Gut hormones continue to show promise on an individual basis as anti-obesity treatments, but combination therapies are needed to achieve beneficial effects comparable to bariatric surgery. Innovative pathways for stimulating native gut hormone secretion may well provide an alternative method for weight loss without necessitating the administration of gut hormone analogues via injection.

Association of Pancreatic Polypeptide with Mild Cognitive Impairment Varies by APOE ε4 Allele.

We conducted a preliminary case–control investigation of the association of pancreatic polypeptide (PP) with mild cognitive impairment (MCI) in 202 MCI cases (mean age, 81.6 years) and 202 age- and sex-matched cognitively normal controls in the Mayo Clinic Study of Aging. Plasma PP was measured and examined as the natural logarithm (continuous) and dichotomized at the median. The OR (95% CI) of MCI increased with increasing PP [1.46 (1.04–2.05)]. There was a negative interaction of PP with apolipoprotein E (APOE) ε4 allele; compared to the reference group (no APOE ε4 allele and low PP), the OR (95% CI) for combinations of ε4 and PP were: 2.64 (1.39–5.04) for APOE ε4 plus low PP; 2.09 (1.27–3.45) for no APOE ε4 plus high PP; and 1.91 (1.04–3.53) for no APOE ε4 plus high PP (P for interaction = 0.017). There was also a trend toward a negative interaction with type 2 diabetes (P for interaction = 0.058). Compared to no diabetes and low PP, the OR (95% CI) was 3.02 (1.22–7.46) for low PP plus diabetes but 1.80 (1.01–3.22) for high PP plus diabetes. Participants with high PP had a greater mean (SD) weight loss (kilograms per decade) than persons with low PP [−2.27 (4.07) vs. −1.61 (5.24); P = 0.016]. MCI cases had a non-significantly greater weight loss per decade compared to controls. These findings suggest that high PP alone or jointly with APOE ε4 allele or type 2 diabetes is associated with MCI, and that high PP may mitigate some effects of APOE ε4 allele and type 2 diabetes on cognition. Potential mechanisms may involve PP-related weight loss and centrally mediated effects of PP on cognition. These findings remain to be validated in other studies.

Autonomic Diabetic Neuropathy Impairs Glucose and Dipeptidyl Peptidase 4 Inhibitor-Regulated Glucagon Concentration in Type 1 Diabetic Patients

Background: Dipeptidyl peptidase 4 inhibitors (DPP4i) could exert their glucagonostatic action through a functional autonomic nervous system independently from insulin secretion. We explored this hypothesis. Methods: We studied C-peptide negative type 1 diabetic patients (T1D) with (AN+) or without (AN-) autonomic neuropathy. Plasma glucagon, active and total glucagon-like peptide-1 (GLP-1), GIP, pancreatic polypeptide (PP), and glucose concentrations were quantified over 180 minutes following a meal test. Furthermore, to increase the plasma concentration of GLP-1 between groups and study its impact on glucagon secretion, 50 mg of vildagliptin and a second meal test were administered to the same patients. Results: The plasma concentration of glucagon was higher in AN+ patients than in AN- patients, which was associated with lower PP and active GLP-1 plasma concentrations. This first set of data suggest that AN, presumably involving parasympathetic activity, results in loss of glucose-regulated glucagon secretion. After DPP4i treatment, AN+ patients lost the ability to suppress plasma glucagon, and the low plasma PP responses were not restored. Conclusions: We here show that a functional autonomic nervous system is required for the proper control of glucagon secretion. The mechanism is insulin-independent. The glucagonostatic action of DPP4i also requires this mechanism. J Endocrinol Metab. 2015;5(4):229-237 doi: http://dx.doi.org/10.14740/jem289w

Gut satiety hormones and hyperemesis gravidarum.

Hyperemesis gravidarum (HG) is described as unexplained excessive nausea and vomiting during pregnancy. Some gut hormones that regulate appetite may have important role in etiopathogenesis of HG and weight changes during pregnancy. In this study, levels of gut satiety hormones were evaluated in pregnant women with HG. This prospective case-control study was conducted in 30 women with HG and 30 healthy pregnant women without symptoms of HG. Fasting venous blood samples were taken from all subjects for measurement of plasma gut hormone levels; obestatin (pg/mL), peptide YY (PYY), pancreatic polypeptide (PP) and cholecystokinin (CCK). Plasma PYY and PP levels were significantly higher in HG group. The most important parameter in diagnosis of HG was plasma PP level. Simple use of PP level led to the diagnosis 91.1 % of HG cases correctly. The single most important parameter in the prediction of HG was also PP level. Anorexigenic gut hormones might have important role in etiopathogenesis of hyperemesis gravidarum and weight changes during pregnancy.

Circulating pancreatic polypeptide concentrations predict visceral and liver fat content.

Context and objective:No current biomarker can reliably predict visceral and liver fat content, both of which are risk factors for cardiovascular disease. Vagal tone has been suggested to influence regional fat deposition. Pancreatic polypeptide (PP) is secreted from the endocrine pancreas under vagal control. We investigated the utility of PP in predicting visceral and liver fat.Patients and Methods:Fasting plasma PP concentrations were measured in 104 overweight and obese subjects (46 men and 58 women). In the same subjects, total and regional adipose tissue, including total visceral adipose tissue (VAT) and total subcutaneous adipose tissue (TSAT), were measured using whole-body magnetic resonance imaging. Intrahepatocellular lipid content (IHCL) was quantified by proton magnetic resonance spectroscopy.Results:Fasting plasma PP concentrations positively and significantly correlated with both VAT (r = 0.57, P < .001) and IHCL (r = 0.51, P < .001), but not with TSAT (r = 0.02, P = .88). Fasting PP concentrations independently predicted VAT after controlling for age and sex. Fasting PP concentrations independently predicted IHCL after controlling for age, sex, body mass index (BMI), waist-to-hip ratio, homeostatic model assessment 2-insulin resistance, (HOMA2-IR) and serum concentrations of triglyceride (TG), total cholesterol (TC), and alanine aminotransferase (ALT). Fasting PP concentrations were associated with serum ALT, TG, TC, low- and high-density lipoprotein cholesterol, and blood pressure (P < .05). These associations were mediated by IHCL and/or VAT. Fasting PP and HOMA2-IR were independently significantly associated with hepatic steatosis (P < .01).Conclusions:Pancreatic polypeptide is a novel predictor of visceral and liver fat content, and thus a potential biomarker for cardiovascular risk stratification and targeted treatment of patients with ectopic fat deposition.