PYY Responses Research Articles

Pancreatic and gut hormone responses to mixed meal test in post-chronic pancreatitis diabetes mellitus

ObjectiveMore than one-third of chronic pancreatitis patients will eventually develop diabetes, recently classified as post-chronic pancreatitis diabetes mellitus (PPDM-C). This study was aimed to investigate the pancreatic and gut hormone responses to a mixed meal test in PPDM-C patients, compared with non-diabetic chronic pancreatitis (CP), and type 2 diabetes patients or healthy controls. Design and methodsSixteen patients with PPDM-C, 12 with non-diabetic CP as well as 10 with type 2 diabetes and healthy controls were recruited. All participants underwent mixed meal tests, and blood samples were collected for measurements of blood glucose, C-peptide, insulin, glucagon, pancreatic polypeptide (PP), ghrelin, peptide YY, glucagon like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP). Indices of insulin sensitivity and secretion were calculated. Repeated measures analysis of variance was performed. ResultsParticipants with PPDM-C exhibited decreases in both fasting and postprandial responses of C-peptide (P < 0.001), insulin (P < 0.001), ghrelin (P < 0.001) and PYY (P = 0.006) compared to participants with type 2 diabetes and healthy controls. Patients with CP showed blunted glucagon, PP and incretin reactions, while the responses were increased in patients with PPDM-C compared to controls. The level of insulin sensitivity was higher for PPDM-C than type 2 diabetes (P < 0.01), however the indices for early/late-phase and overall insulin secretion (P < 0.01) were lower. ConclusionsPatients with PPDM-C are characterized by decreased C-peptide, insulin, ghrelin and PYY responses, and similar levels of glucagon, PP, GIP and GLP-1 compared to those with type 2 diabetes. The above findings, when confirmed in a larger population, may prove helpful to establish the diagnosis of PPDM-C, and should promote study on underlying pathophysiological mechanisms.

47 Quantitative evaluation of hunger in pregnant sows: metabolic and hormonal responses to feeding frequency under limit-fed regime

Abstract The objectives of the study were to determine the pattern of glucose, insulin, active ghrelin, and total PYY responses and indirectly quantify perceived hunger in pregnant sows under-limit fed conditions. Eighteen sows [(Landrace × Yorkshire); BW 211.86 ± 1.29 kg; parity 3.80 ± 0.16; backfat 13.50 ± 0.25 mm)] were sampled from 180 sows. Sows were blocked by parity and BW and randomly assigned to 1 of 3 treatments in a RCBD. Treatments included sows fed once at [0730 h (Control, T1), twice [half ration at 0730 and 1530 h (T2)], or thrice [one-third portion at 0730, 1130, and 1530 h (T3)]. The daily feed quantity was kept at 1.25× maintenance energy intake (100 × (BW)0.75) kcal ME/d. Sows received corn-soybean meal-based diet which provided 6935 kcal ME/d and SID Lys:ME of 1.71 g/Mcal from d 30 to 60 of gestation. Hunger was quantified using total area under the curve (AUC) of the hormonal responses. Data analysis was done using PROC MIXED and GLIMMIX procedure of SAS. Sow was the experimental unit. Adjustment for multiple comparisons was by Tukey’s method. The control sows had greater 23-h mean glucose concentration than sows fed 3× daily (P = 0.002). Active ghrelin concentration for sows fed 3× daily tended to be lower (P = 0.063) compared with control sows but reduced (P = 0.018) relative to sows fed 2× daily. In conclusion, sows fed 3× daily had 9.0% reduction in 23-h glucose total AUC, 42.5% greater 23-h insulin total AUC, 27.4% reduction in active ghrelin total AUC, and 14.2% greater PYY total AUC compared with pregnant sows fed 1× daily. It is suggested that hunger in pregnant sows occurs at active ghrelin/total PYY ratio of 5.06 ± 0.20 and at a mean plasma glucose concentration of 70.37 ± 1.39 mg/dL and below.

Co-ingestion of whey protein hydrolysate with milk minerals rich in calcium potently stimulates glucagon-like peptide-1 secretion: an RCT in healthy adults

PurposeTo examine whether calcium type and co-ingestion with protein alter gut hormone availability.MethodsHealthy adults aged 26 ± 7 years (mean ± SD) completed three randomized, double-blind, crossover studies. In all studies, arterialized blood was sampled postprandially over 120 min to determine GLP-1, GIP and PYY responses, alongside appetite ratings, energy expenditure and blood pressure. In study 1 (n = 20), three treatments matched for total calcium content (1058 mg) were compared: calcium citrate (CALCITR); milk minerals rich in calcium (MILK MINERALS); and milk minerals rich in calcium plus co-ingestion of 50 g whey protein hydrolysate (MILK MINERALS + PROTEIN). In study 2 (n = 6), 50 g whey protein hydrolysate (PROTEIN) was compared to MILK MINERALS + PROTEIN. In study 3 (n = 6), MILK MINERALS was compared to the vehicle of ingestion (water plus sucralose; CONTROL).ResultsMILK MINERALS + PROTEIN increased GLP-1 incremental area under the curve (iAUC) by ~ ninefold (43.7 ± 11.1 pmol L−1 120 min; p < 0.001) versus both CALCITR and MILK MINERALS, with no difference detected between CALCITR (6.6 ± 3.7 pmol L−1 120 min) and MILK MINERALS (5.3 ± 3.5 pmol L−1 120 min; p > 0.999). MILK MINERALS + PROTEIN produced a GLP-1 iAUC ~ 25% greater than PROTEIN (p = 0.024; mean difference: 9.1 ± 6.9 pmol L−1 120 min), whereas the difference between MILK MINERALS versus CONTROL was small and non-significant (p = 0.098; mean difference: 4.2 ± 5.1 pmol L−1 120 min).ConclusionsWhen ingested alone, milk minerals rich in calcium do not increase GLP-1 secretion compared to calcium citrate. Co-ingesting high-dose whey protein hydrolysate with milk minerals rich in calcium increases postprandial GLP-1 concentrations to some of the highest physiological levels ever reported. Registered at ClinicalTrials.gov: NCT03232034, NCT03370484, NCT03370497.

Effect of Macronutrient Type and Gastrointestinal Release Site on PYY Response in Normal Healthy Subjects.

Enteroendocrine L cells release satiety inducing hormones in response to stimulation by luminal macronutrients. We sought to profile the differential effect of macronutrient type and site of release on circulating concentrations of the L cell-derived enteroendocrine hormone peptide tyrosine tyrosine (amino acids 1 to 36) (PYY). Eight healthy volunteers were recruited to a randomized, double-blinded, six-way crossover study. At each visit, the participants consumed a 500-kcal drink containing carbohydrate, protein, or fat in either gastric or small intestinal release formulations. Plasma PYY concentrations and hunger ratings were assessed for 3 hours after consumption of the test drink. The food intake was recorded thereafter at an ad libitum lunch. Microcapsular formulations targeting the distal small intestinal delivery of fat, but not carbohydrate or protein, markedly enhance PYY release relative to macronutrient delivery in gastric release formulations. Food intake at an ad libitum meal was lowest after consumption of the formulation releasing fat at the distal small intestine. Targeting of fat to the distal small intestine in delayed release microcapsules enhanced PYY release and was associated with reductions in food intake.

Metabolic consequences of discretionary fortified beverage consumption containing excessive vitamin B levels in adolescents.

Over the past decade, there has been a substantial increase in the number of beverage products containing added vitamins and minerals. Often viewed as a healthier choice by consumers, the metabolic impacts of excessive vitamin consumption are relatively unknown, especially in children. The aim of this study was to examine the effects of a widely available, vitamin fortified beverage (5h Energy Decaffeinated) on insulin sensitivity, metabolic hormones and serum metabolomic responses in adolescents. Twenty adolescents (13-19y, 10M/10F) completed two randomized trials, consuming either coloured water as placebo (PL) or a vitamin fortified, sugar free beverage (FB, 1.5ml/kg) 40min prior to a modified oral glucose tolerance test (OGTT, 1.75g/kg glucose). Samples were collected at baseline and at 30, 45, 60, 90 and 120min during the OGTT. No differences in blood glucose response were observed between the treatments. However, compared to PL, postprandial plasma C-peptide and insulin excursion was significantly greater with FB, resulting in a 28% decline in the insulin sensitivity index. This was accompanied by elevated GLP-1, glucagon and PYY responses with FB compared to PL. Serum metabolomics (1H-NMR) analysis also revealed perturbations to vitamin B-linked one carbon metabolism flux with FB consumption that became more pronounced over time. These included a transient reduction in homocysteine flux accompanied by increases in betaine, vitamin B6, vitamin B12, choline, folate and taurine. Although these impacts are likely short-lived, results show that beverages fortified with excessive amounts of vitamins are not metabolically inert, but likely result in greater insulin secretion, differential gut hormone secretion and elevated one-carbon flux to process the excessive vitamin loads.

Fructose intervention for 12 weeks does not impair glycemic control or incretin hormone responses during oral glucose or mixed meal tests in obese men

Background and aimsIncretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. Methods and resultsAs many as 66 obese (BMI 26–40 kg/m2) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). ConclusionIn obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge.

Changes in PYY and gastric emptying across the phases of the menstrual cycle and the influence of the ovarian hormones

Nutrition-related studies avoid the participation of pre-menopausal women due to the potential effect of the menstrual cycle (MC) on their appetite regulation. It is generally accepted that women increase their energy intake during the luteal phase (LPh) compared to the follicular (FPh), however what happens in the menstrual phase (MPh) and how this might be regulated remains uncertain. Although some research indicates changes in the gastric emptying (GE) velocity, whether PYY is affected by the MC phase, remains unknown. The aim of this study was to assess whether eating the same breakfast in each of the three MC phases would change the GE time, the PYY response and post-prandial satiety such that they might affect subsequent food intake. Furthermore, the aim was to associate any potential differences to the fluctuations in estradiol (E2) and progesterone (P4) within a MC. Nine naturally cycling women attended to the laboratory to consume a standardised breakfast on three occasions, each of them representing one of the MC phases. Breath samples to measure GE time, plasma samples to quantify PYY levels and hunger scores were collected for a total of 4 h after which food intake was assessed by an ad-libitum buffet lunch. GE and PYY levels changed significantly across the phases of the MC (p < 0.05). GE was correlated to P4 and E2-P4 ratio (r = −0.5 and 0.4, respectively). To conclude, the appetite regulators PYY and GE time change depending upon the MC phases with GE time associated with the ovarian hormone levels which suggests the necessity of controlling the MC phase in studies looking at the appetite response.

Bile acids and gut peptide secretion after bariatric surgery: A 1‐year prospective randomized pilot trial

Increased delivery of bile acid salts (BA) to distal L-cells and altered TGR5 receptor activation may contribute to the early and substantial increases in gut peptide secretion seen after bariatric surgery. To further elucidate a potential role of BA in the secretion of GLP-1 and PYY, we analyzed plasma BA concentrations in 14 morbidly obese patients undergoing gastric bypass or sleeve gastrectomy in a prospective, randomized 1-year trial. Patients received a standard test meal and blood was collected before and after eating, prior to, and 1 week, 3 months, and 12 months after surgery. Pre-surgery, basal BA concentrations were significantly lower in bariatric patients than in healthy controls. One year post-surgery, bariatric patients expressed variably increased BA concentrations (gastric bypass patients ∼2 fold increase, P ≤ 0.05). However, whereas in both patient groups, marked increases in GLP-1 and PYY and improved glycemic control was seen already 1 week and 3 months post-surgery, changes in plasma BA followed a different pattern: basal and postprandial plasma BA concentrations increased much slower, more progressively with significant increases only 1-year post-surgery. Based on these findings, BA do not appear to be key mediators of the early increase in GLP-1 and PYY response in post-bariatric patients.

Effects of Increased Dietary Protein at Breakfast on Appetite Control &amp; Energy Intake Throughout the Day in Overweight ‘Breakfast Skipping’ Teen Girls

PurposeTo examine whether a higher‐protein (HP) vs. normal‐protein (NP) breakfast leads to daily improvements in appetite control and energy intake regulation in overweight ‘breakfast skipping’ (BS) girls.MethodsTwenty girls (age 19 ±1 y; BMI 28.6 ± 0.7 kg/m2; BS 6 ± 1 x/wk) randomly consumed 350 kcal breakfast meals containing NP cereals (15% Protein (13 g); 65% CHO; 20% Fat) or HP, egg and beef‐based foods (40% Protein (35 g); 40% CHO; 20% Fat) for 7 consecutive days. On day 7 of each pattern, a 10 h testing day was completed. At the onset of the respective breakfast, perceived appetite/satiety questionnaires and blood sampling were completed every 30 min. A standard lunch occurred 4 h post‐breakfast; an ad libitum dinner was consumed 4 h post‐lunch, and ad libitum snacks were packed out to be consumed at home throughout the evening.ResultsThe HP breakfast led to greater increases in perceived satiety, reductions in ghrelin, and increases in PYY responses vs. NP (p&lt;0.05, all). HP breakfast also led to reduced snacking, particularly of foods high in fat vs. NP (energy content: 486 ± 84 vs. 621 ± 110 kcal; p=0.07; fat content: 17.4 ± 3.6 vs. 23.8 ± 4.4 g; p&lt;0.05).ConclusionsA higher protein breakfast meal containing 35 g of protein improved appetite control, satiety, and reduced unhealthy snacking in ‘breakfast skipping’ overweight teenage girls. Support: Beef Checkoff &amp; the American Egg Board/Egg Nutrition Center

Reply to Gastric Emptying After Sleeve Gastrectomy (OBSU-D-11-00201)

Dear Editor, We thank Melissas and Daskalakis for their interest in our study “Gastric emptying and postprandial PYY response after biliopancreatic diversion with duodenal switch”. We share the view that methodological differences in gastric emptying studies are a problem. The three listed studies [1–3], as well as new MRI-based work [4], have all used different meals with different caloric content, making comparisons very challenging. Moreover, these studies examine gastric emptying after the gastric sleeve procedure. The procedure studied in our paper [5], biliopancreatic diversion with duodenal switch (BPD-DS), is different to gastric sleeve in several respects, which is important when discussing results. First, the gastric tube empties directly into the proximal ileum, in contrast to the maintained passage into the untouched duodenum after sleeve gastrectomy. Second, the vagal innervation of the pylorus is most likely more affected by BPD-DS as compared to gastric sleeve since the proximal duodenum is circumferentially dissected and transected in BPD-DS. We also agree that gastric emptying is influenced by age, gender, physical activity levels, meal size and energy density among other factors which is why we state that interpreting our finding is a challenge [5]. We speculate that the difference in postoperative anatomy (and thus neurohormonal response to a meal) could explain our finding of a short median half-time (28 min) in our 20 studied BPD-DS patients versus 38–62 min in the gastric sleeve studies. We do not think, however, that this comparison should be made to strongly because of the differences between the operations discussed above. We present gastric emptying data after BPD-DS. We had to use different test meals for the gastric emptying and PYY studies. This was not ideal. Identical conditions in a large, homogenous group (minimal spread in age and BMI) in patients with the same gender, having repeated examinations, would be perfect for research. However, this is often not possible in clinical studies. For the scintigraphic studies, we used a quarter of a standardized meal developed after a national, multicentre study [6], since we wanted to be sure that the whole meal could be accommodated in the gastric remnant (which can be as small as 88 ml after BPD-DS [7]) before the first scan was taken. A standardized and uniform test procedure, adapted for the post-bariatric surgery setting would be ideal for our future joint understanding of this field.

In adults with Prader–Willi syndrome, elevated ghrelin levels are more consistent with hyperphagia than high PYY and GLP-1 levels

Prader-Willi syndrome (PWS) is a leading genetic cause of obesity, characterized by hyperphagia, endocrine and developmental disorders. It is suggested that the intense hyperphagia could stem, in part, from impaired gut hormone signaling. Previous studies produced conflicting results, being confounded by differences in body composition between PWS and control subjects. Fasting and postprandial gut hormone responses were investigated in a cross-sectional cohort study including 10 adult PWS, 12 obese subjects matched for percentage body fat and central abdominal fat, and 10 healthy normal weight subjects. PYY[total], PYY[3-36], GLP-1[active] and ghrelin[total] were measured by ELISA or radioimmunoassay. Body composition was assessed by dual energy X-ray absorptiometry. Visual analog scales were used to assess hunger and satiety. In contrast to lean subjects (p<0.05), PWS and obese subjects were similarly insulin resistant and had similar insulin levels. Ghrelin[total] levels were significantly higher in PWS compared to obese subjects before and during the meal (p<0.05). PYY[3-36] meal responses were higher in PWS than in lean subjects (p=0.01), but not significantly different to obese (p=0.08), with an additional non-significant trend in PYY[total] levels. There were no significant differences in self-reported satiety between groups, however PWS subjects reported more hunger throughout (p=0.003), and exhibited a markedly reduced meal-induced suppression of hunger (p=0.01) compared to lean or obese subjects. Compared to adiposity-matched control subjects, hyperphagia in PWS is not related to a lower postprandial GLP-1 or PYY response. Elevated ghrelin levels in PWS are consistent with increased hunger and are unrelated to insulin levels.

Pork, beef and chicken have similar effects on acute satiety and hormonal markers of appetite

The effects of three different meat-containing breakfast meals (pork, beef or chicken) on acute satiety and appetite regulatory hormones were compared using a within-subjects study design. Thirty fasting non-smoking pre-menopausal women attended a research centre on three test days to consume, a meat-containing meal matched in energy (kJ) and protein content, palatability, and appearance. No difference was found between meat groups for either energy intake or macronutrient profile of food consumed at a subsequent ad libitum buffet lunch, or over the rest of the day. Visual Analogue Scale (VAS) ratings for hunger and satiety over an 180min period did not differ between test meals. After consumption of the test meals, a significant difference was found in PYY response between pork and chicken meals (P=0.027) but not for levels of CCK, ghrelin, insulin or glucose. This study positions pork, beef, and chicken as equal in their effect on satiety and release of appetite-related intestinal hormones and of insulin.

Gut Transit Is Associated With Gastrointestinal Symptoms and Gut Hormone Profile in Patients With Cirrhosis

Liver cirrhosis is associated with increased prevalence of gastrointestinal symptoms, insulin resistance, and altered gut transit. We aimed to assess the prevalence of gut transit abnormalities in patients with cirrhosis, compared with healthy controls, and to evaluate the relation of gut transit with gastrointestinal symptoms and postprandial glucose and hormone profiles. Half gastric emptying, small bowel residence, and colonic filling times were measured with a validated radiologic procedure in 42 consecutive patients with cirrhosis. In a subgroup of 25 patients, gastrointestinal symptoms were evaluated by using a validated questionnaire and a caloric satiation test. Postprandial glucose, insulin, leptin, ghrelin, glucagon-like peptide 1, and PYY responses were also studied. Eighty-three healthy subjects served as controls for the transit studies and 10 for the hormone analyses. Of patients with cirrhosis, 24% had delayed gastric emptying and 38% had prolonged small bowel transit (P < .05 compared with controls). Delayed gastric emptying was related to postprandial fullness and prolonged small bowel transit to diarrhea and abdominal pain (P < .05 for all). The patients with cirrhosis had increased postprandial glucose, insulin, and glucagon-like peptide 1 responses and reduced postprandial ghrelin. Delayed gastric emptying was related to increased postprandial glucose and reduced postprandial ghrelin. Prolonged small bowel transit was related to increased postprandial glucose and insulin and reduced postprandial ghrelin. A high proportion of patients with cirrhosis exhibit delayed gastric emptying or small bowel transit, which is related to gastrointestinal symptoms. Postprandial hyperglycemia, hyperinsulinemia, and hypoghrelinemia might be linked to delayed gut transit in cirrhosis.

Proximal and distal gut hormone secretion in irritable bowel syndrome

Objective. Sensory and motor dysfunctions of the gut are both important characteristics of irritable bowel syndrome (IBS). Several gut peptides contribute to the regulation of gastrointestinal function but little is known about gut hormone secretion in IBS. Material and methods. We evaluated perceptual thresholds and fasting and postprandial plasma levels of proximal (cholecystokinin (CCK), motilin) and distal (peptide YY) gut peptides up to 1 h after ingestion of a high caloric meal in 99 IBS patients and 40 age- and gender-matched healthy controls. Results. Fasting plasma CCK levels were significantly elevated in patients (1.2±0.8 pM) compared with those in controls (0.8±0.7 pM, p=0.006), as was the incremental postprandial CCK response (72±73 versus 40±42 pM·60 min, respectively; p=0.003). No differences in fasting and postprandial motilin or PYY levels were found. The postprandial PYY response was significantly increased in hypersensitive compared to normosensitive patients (215±135 versus 162±169 pM, p=0.048). Patients with a diarrhoea predominant bowel habit had higher fasting motilin levels compared to constipated patients or alternating type IBS patients (82.1±36.5 versus 60.8±25.1 versus 57.5±23.9 pM, one-way ANOVA p=0.003). Conclusions. IBS patients have increased fasting and postprandial plasma levels of CCK. Changes in plasma levels of motilin and PYY may contribute to the clinical expression of IBS, such as the presence of visceral hypersensitivity or a predominant bowel habit.

Multiple Y receptors mediate pancreatic polypeptide responses in mouse colon mucosa

A functional study has been performed to characterise the Y receptors responsible for NPY, PYY and PP-stimulated responses in mouse colonic mucosal preparations. Electrogenic ion secretion was stimulated with VIP following which NPY, PYY and PP analogues were, to varying degrees, inhibitory. PYY(3-36), hPP, Gln 23hPP and rPP were effective but less potent than full length PYY, NPY or their Pro 34-substituted analogues, while the Y 5 agonist Ala 31, Aib 32hNPY was the least active peptide tested. The Y 1 antagonists, BIBP3226 and BIBO3304 virtually abolished Pro 34PYY and PYY responses while PYY(3-36) responses were selectively inhibited by the Y 2 antagonist, BIIE0246. A combination of BIBO3304 and BIIE0246 also partially attenuated hPP responses, leaving residual effects that were most probably Y 4-mediated. Thus we conclude that Y 1, Y 2 and Y 4 receptors attenuate ion secretion in mouse colon.

Is diarrhea complicating bolus nasogastric tube feeding caused by an abnormal PYY response?

Is diarrhea complicating bolus nasogastric tube feeding caused by an abnormal PYY response?