Effect of ghrelin on glucose tolerance, gut hormones, appetite, and food intake after sleeve gastrectomy.

Ghrelin is an appetite-stimulating hormone secreted from the gastric mucosa in the fasting state, and secretion decreases in response to food intake. After sleeve gastrectomy (SG), plasma concentrations of ghrelin decrease markedly. Whether this affects appetite and glucose tolerance postoperatively is unknown. We investigated the effects of ghrelin infusion on appetite and glucose tolerance in individuals with obesity before and 3 mo after SG. Twelve participants scheduled for SG were included. Before and 3 mo after surgery, a mixed-meal test followed by an ad libitum meal test was performed with concomitant infusions of acyl-ghrelin (1 pmol/kg/min) or placebo. Infusions began 60 min before meal intake to reach a steady state before the mixed-meal and were continued throughout the study day. Two additional experimental days with 0.25 pmol/kg/min and 10 pmol/kg/min of acyl-ghrelin infusions were conducted 3 mo after surgery. Both before and after SG, postprandial glucose concentrations increased dose dependently during ghrelin infusions compared with placebo. Ghrelin infusions inhibited basal and postprandial insulin secretion rates, resulting in lowered measures of ß-cell function, but no effect on insulin sensitivity was seen. Ad libitum meal intake was unaffected by the administration of ghrelin. In conclusion, ghrelin infusion increases postprandial plasma glucose concentrations and impairs ß-cell function before and after SG but has no effect on ad libitum meal intake. We speculate that the lower concentration of ghrelin after SG may impact glucose metabolism following this procedure.NEW & NOTEWORTHY Ghrelin's effect on glucose tolerance and food intake following sleeve gastrectomy (SG) was evaluated. Acyl-ghrelin was infused during a mixed-meal and ad libitum meals before and 3 mo after surgery. Postprandial glucose concentrations increased during ghrelin infusions, both before and after surgery, while insulin production was inhibited. However, ad libitum meal intake did not differ during ghrelin administration compared with placebo. The decreased ghrelin concentration following SG may contribute to the glycemic control after surgery.

Clinical value of prokineticin 2 in the diagnosis of neonatal necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is an inflammatory and necrotizing intestinal emergency that occurs in preterm infants and low birth weight newborns; however, no specific serum biomarkers for the diagnosis of NEC has been identified so far. METHODS: Serum samples were collected from healthy neonatal controls and patients with NEC newly admitted to the Children's Hospital of Chongqing Medical University. ELISA was used to measure serum PK2 levels, and ROC curve analysis was sued to evaluate the diagnostic efficacy of PK2 and other clinical biomarkers. RESULTS: Serum PK2 levels in the NEC group (n = 53) were significantly lower than those in the control group (n = 18), but increased to near-normal levels after the postoperative recovery period. The NLR value of NEC group was higher than that of control group (P < 0.05). There was no significant difference in WBC and PLT count between NEC group and control group (P > 0.05). Serum CRP and PCT levels in NEC group were significantly higher than those in control group (P < 0.001 for CRP and P < 0.05 for PCT, respectively). After surgery, serum CRP, NLR and PCT levels were lower than before surgery, while serum PK2 levels were higher than before surgery (P < 0.05). The areas under the ROC curve (AUC) of PK2, PCT and CRP for the diagnosis of NEC were 0.837, 0.662 and 0.552, respectively. The AUC of PK2 combined with PCT, PK2 combined with CRP, and PK2 combined with PCT and CRP were 0.908, 0.854 and 0.981, respectively. PK2 exhibited the highest diagnostic efficacy for NEC. CONCLUSION: PK2 has higher diagnostic efficacy than PCT and CRP in the diagnosis of NEC; the combination of PK2 and PCT or CRP can significantly improve its diagnostic efficiency, especially when the three are combined at the same time.

Augmented gut hormone response to feeding in older adults exhibiting low appetite.

Age-related changes in gut hormones may play a role in anorexia of ageing. The aim of this study was to determine concentrations of ghrelin, PYY, and GLP-1 in older adults exhibiting an anorexia of ageing phenotype. Thirteen older adults with healthy appetite (OA-HA; 8f, 75 ± 7 years, 26.0 ± 3.2 kg m-2), fifteen older adults with low appetite (OA-LA; 10f, 72 ± 7 years, 23.6 ± 3.1 kg m-2), and twelve young adults (YA; 6f, 22 ± 2 years, 24.4 ± 2.0 kg m-2) completed the study. Healthy appetite and low appetite were determined based on BMI, habitual energy intake, self-reported appetite, and laboratory-assessed ad libitum lunch intake. Participants provided a fasted measure of subjective appetite and blood sample (0 min) before consuming a standardised breakfast (450 kcal). Appetite was measured and blood samples were drawn throughout a 240-min rest period. At 240 min, an ad libitum lunch meal was consumed. Relative intake at lunch (expressed as percentage of estimated total energy requirement) was lower for OA-LA (19.8 ± 7.7%) than YA (41.5 ± 9.2%, p < 0.001) and OA-HA (37.3 ± 10.0%, p < 0.001). Ghrelin suppression was greater for OA-LA (net AUC, -78719 ± 74788 pg mL-1·240min-1) than both YA (-23899 ± 27733 pg mL-1·240min-1, p = 0.016) and OA-HA (-21144 ± 31161 pg mL-1·240min-1, p = 0.009). There were trends for higher GLP-1 concentrations in OA-LA compared with YA at 90 min (8.85 ± 10.4 pM vs. 1.88 ± 4.63 pM, p = 0.073) and 180 min (5.00 ± 4.71 pM vs. 1.07 ± 2.83 pM, p = 0.065). There was a trend for a greater PYY response for OA-LA compared with OA-HA (net AUC p = 0.062). "Anorexigenic response score" - a composite score of gut hormone responses to feeding - showed greater anorexigenic response in OA-LA, compared with YA and OA-HA. No differences were seen in subjective appetite. These observations suggest augmented anorexigenic responses of gut hormones to feeding may be causal mechanisms of anorexia of ageing.

Appetite, food intake, and gut hormone responses to glycomacropeptide protein ingestion in older adults: A feasibility, acceptability, and pilot study.

Glycomacropeptide (GMP) has a unique amino acid profile which may make less satiating than other dietary proteins. This study assessed the feasibility and likely acceptability of a leucine-enriched GMP drink and determined appetite response in older adults (OA). Thirteen OA (11f; 70 ± 4 years) were recruited for sensory assessments of a leucine-enriched GMP drink when mixed with water and with fruit smoothie, compared with whey protein isolate (WHEY). Participants also partook in a single focus group exploring acceptability to protein and supplementation. Separately, a counterbalanced, double-blind study with twelve OA (8f; 69 ± 3 years) was conducted to determine appetite and gut hormone responses. Fasting subjective appetite was recorded using visual analogue scales and a fasted venous blood sample was collected (to measures acyl-ghrelin, PYY, GLP-1, and CCK) before participants consumed either: GMP protein (27g + 3g leucine, 350 mL water), WHEY (30g, 350 mL water), or water. Participants rested for 240 min, with appetite measures and blood sampling throughout. An ad libitum pasta-based meal was then consumed. Sensory testing revealed low pleasantness rating for GMP in water vs. WHEY (16 ± 14 vs 31 ± 24, p = 0.016). GMP addition to smoothie reduced pleasantness (26 ± 21 vs. 61 ± 29, p = 0.009) and worsened the aroma (46 ± 15 vs. 69 ± 28, p = 0.014). The focus group revealed uncertainty of protein needs and a scepticism of supplements, with preference for food. Gut hormone response did not differ between GMP and WHEY (nAUC for all gut hormones p > 0.05). There was no difference between conditions for lunch ad libitum intake (549 ± 171 kcal, 512 ± 238 kcal, 460 ± 199 kcal for GMP, WHEY, and water, p = 0.175), or for subjective appetite response. Leucine-enriched GMP was not less satiating than WHEY, and low palatability and scepticism of supplements question the likely acceptability of GMP supplementation. Providing trusted nutritional advice and food enrichment/fortification may be preferred strategies for increasing protein intake in OA.

Effects of remimazolam tosilate on gastrointestinal hormones and gastrointestinal motility in patients undergoing gastrointestinal endoscopy with sedation: a randomized control trial.

PURPOSE: To investigate the impacts of remimazolam tosilate on gastrointestinal hormones and motility in patients undergoing gastrointestinal endoscopy with sedation. METHODS: A total of 262 American Society of Anesthesiologists Physical Status I or II patients, aged 18-65 years, scheduled for gastrointestinal endoscopy with sedation, were randomly allocated into two groups (n = 131 each): the remimazolam tosilate group (Group R) and the propofol group (Group P). Patients in Group R received 0.2-0.25 mg/Kg remimazolam tosilate intravenously, while those in Group P received 1.5-2.0 mg/kg propofol intravenously. The gastrointestinal endoscopy was performed when the Modified Observer's Assessment of Alertness/Sedation scores were ≤3. The primary endpoints included the endoscopic intestinal peristalsis rating by the endoscopist; serum motilin and gastrin levels at fasting without gastrointestinal preparation (T0), before gastrointestinal endoscopy (T1), and before leaving the Post Anesthesia Care Unit (T2); and the incidences of abdominal distension during Post Anesthesia Care Unit. RESULTS: Compared with Group P, intestinal peristalsis rating was higher in Group R (P < .001); Group R showed increased motilin and gastrin levels at T2 compared with Group P (P < .01). There was a rise in motilin and gastrin levels at T1 and T2 compared with T0 and at T2 compared with T1 in both groups (P < .01). The incidence of abdominal distension was lower in Group R (P < .05). CONCLUSION: Compared with propofol used during gastrointestinal endoscopy with sedation, remimazolam tosilate mildly inhibits the serum motilin and gastrin levels, potentially facilitating the recovery of gastrointestinal motility.

The acute effect of fasted exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release compared to fed exercise in healthy individuals: a systematic review and network meta-analysis.

OBJECTIVE: To determine the acute effect of fasted and fed exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release. METHODS: CENTRAL, Embase, MEDLINE, PsycInfo, PubMed, Scopus and Web of Science databases were searched to identify randomised, crossover studies in healthy individuals that compared the following interventions: (i) fasted exercise with a standardised post-exercise meal [FastEx + Meal], (ii) fasted exercise without a standardised post-exercise meal [FastEx + NoMeal], (iii) fed exercise with a standardised post-exercise meal [FedEx + Meal], (iv) fed exercise without a standardised post-exercise meal [FedEx + NoMeal]. Studies must have measured ad libitum meal energy intake, within-lab energy intake, 24-h energy intake, energy expenditure, subjective hunger, acyl-ghrelin, peptide YY, and/or glucagon-like peptide 1. Random-effect network meta-analyses were performed for outcomes containing ≥5 studies. RESULTS: 17 published articles (23 studies) were identified. Ad libitum meal energy intake was significantly lower during FedEx + Meal compared to FedEx + NoMeal (MD: -489 kJ; 95% CI, -898 to -80 kJ; P = 0.019). Within-lab energy intake was significantly lower during FastEx + NoMeal compared to FedEx + NoMeal (MD: -1326 kJ; 95% CI, -2102 to -550 kJ; P = 0.001). Similarly, 24-h energy intake following FastEx + NoMeal was significantly lower than FedEx + NoMeal (MD: -2095 kJ; 95% CI, -3910 kJ to -280 kJ; P = 0.024). Energy expenditure was however significantly lower during FastEx + NoMeal compared to FedEx+NoMeal (MD: -0.67 kJ/min; 95% CI, -1.10 to -0.23 kJ/min; P = 0.003). Subjective hunger was significantly higher during FastEx + Meal (MD: 13 mm; 95% CI, 5-21 mm; P = 0.001) and FastEx + NoMeal (MD: 23 mm; 95% CI, 16-30 mm; P < 0.001) compared to FedEx + NoMeal. CONCLUSION: FastEx + NoMeal appears to be the most effective strategy to produce a short-term decrease in energy intake, but also results in increased hunger and lowered energy expenditure. Concerns regarding experimental design however lower the confidence in these findings, necessitating future research to rectify these issues when investigating exercise meal timing and energy balance. PROSPERO REGISTRATION NUMBER: CRD42020208041. KEY POINTS: Fed exercise with a standardised post-exercise meal resulted in the lowest energy intake at the ad libitum meal served following exercise completion. Fasted exercise without a standardised post-exercise meal resulted in the lowest within-lab and 24-h energy intake, but also produced the lowest energy expenditure and highest hunger. Methodological issues lower the confidence in these findings and necessitate future work to address identified problems.

Serum prokineticin-2 in prepubertal and adult Klinefelter individuals.

The prokineticin-2 (PROK2) is a small peptide belonging to the prokineticin family. In humans and rodents this chemokine is primarily involved in the control of central and peripheral reproductive processes. Klinefelter's syndrome (KS) is the first cause of male genetic infertility, due to an extra X chromosome, which may occur with a classical karyotype (47, XXY) or mosaic forms (46, XY/47, XXY). In affected subjects, pubertal maturation usually begins at an adequate chronological age, but when development is almost complete, they display a primary gonadal failure, with early spermatogenesis damage, and later onset of testosterone insufficiency. Thus, the main aim of the present study was to investigate the serum levels of PROK2 in prepubertal and adult KS patients, comparing them with healthy subjects. We showed for the first time the presence of PROK2 in the children serum but with significant changes in KS individuals. Indeed, compared with healthy subjects characterized by PROK2 serum elevation during the growth, KS individuals showed constant serum levels during the sexual maturation phase (higher during the prepubertal phase but lower during the adult age). In conclusion, these data indicate that in KS individuals PROK2 may be considered a biomarker for investigating the SK infertility process.

Acute exposure to a hot ambient temperature reduces energy intake but does not affect gut hormones in men during rest.

This study examined the effect of ambient temperature on energy intake, perceived appetite and gut hormone responses during rest in men. Thirteen men (age 21·5 (sd 1·4) years; BMI 24·7 (sd 2·2) kg/m2) completed three, 5·5 h conditions in different ambient temperatures: (i) cold (10°C), (ii) thermoneutral (20°C) and (iii) hot (30°C). A standardised breakfast was consumed after fasting measures, and an ad libitum lunch provided at 4-4·5 h. Blood samples (analysed for plasma acylated ghrelin, total peptide tyrosine-tyrosine (PYY) and total glucagon-like peptide 1 (GLP-1) concentrations), perceived appetite and thermoregulatory responses were collected throughout. Linear mixed models were used for statistical analyses. Ad libitum energy intake was 1243 (sd 1342) kJ higher in 10°C and 1189 (sd 1219) kJ higher in 20 v. 30°C (P = 0·002). Plasma acylated ghrelin, total PYY and GLP-1 concentrations did not differ significantly between the conditions (P ≥ 0·303). Sensitivity analyses for the 4 h pre-lunch period showed that perceived overall appetite was lower in both 30 and 10°C when compared with 20°C (P ≤ 0·019). In conclusion, acutely resting in a hot compared with a thermoneutral and cold ambient temperature reduced lunchtime ad libitum energy intake in healthy men. Suppressed perceived appetite may have contributed to the reduced energy intake in the hot compared with thermoneutral ambient temperature, whereas gut hormones did not appear to play an important role.

Plasma Prokineticin 1, a prognostic biomarker in colorectal cancer patients with curative resection: a retrospective cohort study.

BACKGROUND: Prokineticin 1 (PROK1) was reported as an angiogenic factor, which is associated with tumor progression, cell invasion, and metastasis in colorectal cancer. Although the association between PROK1 expression in primary cancer lesion and patient prognosis was reported, it is unclear whether plasma PROK1 concentration may be a predictive factor in colorectal cancer patients. This study investigated the association between PROK1 concentration in plasma and prognosis in colorectal cancer patients. METHODS: We measured preoperative PROK1 plasma levels using ELISA method, while PROK1 expression in primary cancer lesion was evaluated using immunohistochemistry (IHC). The association between plasma PROK1 levels and cancer-related survival rate (CRS) was evaluated. Additionally, we examined whether simultaneous PROK1 expression in both primary cancer lesions and plasma was correlated with CRS. The cancer-related survival rate was calculated using the Kaplan-Meier method, and survival estimates were compared using the log-rank test. RESULTS: We have gathered eligible 130 CRC patients retrospectively. Out of 130 patients, 61 (46.9%) were positive on IHC in primary cancer, and 69 (53.1%) were negative, while 43 (33.1%) had high-value PROK1 in plasma. Out of these 43, 30 (25.4%) also had concomitant higher IHC expression in primary cancer. The plasma PROK1 levels tended to increase with advancing stages. The plasma PROK1-positive group had a lower 5-year CRS than the negative group (63.6% vs. 88.2%; P = 0.006). Additionally, simultaneous PROK1 expression was associated with a more significant decrease of 5-year CRS than both negative groups in all stages (76.2% vs. 92.5%; P = 0.003) and stage III (59.3% vs. 84.5%; P = 0.047). Multivariate analysis showed simultaneous PROK1 expression was independently associated with worse CRS (HR, 1.97; 95% CI 1.20­3.24, P < 0.01). CONCLUSION: PROK1 expression in preoperative plasma reflects poor prognosis in patients undergoing curative resection for colorectal cancer. The plasma PROK1 level may be a potential predictive marker, especially in stage III colorectal cancer patients.

Postprandial Nutrient Handling and Gastrointestinal Hormone Secretion After Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy.

BACKGROUND & AIMS: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) induce substantial weight loss and improve glycemic control in patients with type 2 diabetes, but it is not clear whether these occur via the same mechanisms. We compared absorption rates of glucose and protein, as well as profiles of gastro-entero-pancreatic hormones, in patients who had undergone SG or RYGB vs controls. METHODS: We performed a cross-sectional study of 12 patients who had undergone sleeve gastrectomy, 12 patients who had undergone RYGB, and 12 individuals who had undergone neither surgery (controls), all in Denmark. Study participants were matched for body mass index, age, sex, and postoperative weight loss, and all had stable weights. They received continuous infusions of stable isotopes of glucose, glycerol, phenylalanine, tyrosine, and urea before and during a mixed meal containing labeled glucose and intrinsically phenylalanine-labeled caseinate. Blood samples were collected for 6 hours, at 10- to 60-minute intervals, and analyzed. RESULTS: The systemic appearance of ingested glucose was faster after RYGB and SG vs controls; the peak glucose appearance rate was 64% higher after RYGB, and 23% higher after SG (both P < .05); the peak phenylalanine appearance rate from ingested casein was 118% higher after RYGB (P < .01), but similar between patients who had undergone SG and controls. Larger, but more transient increases in levels of plasma glucose and amino acids were accompanied by higher secretion of insulin, glucagon-like peptide 1, peptide YY, and cholecystokinin after RYGB, whereas levels of ghrelin were lower after SG, compared with RYGB and controls. Total 6-hour oral recovery of ingested glucose and protein was comparable among groups. CONCLUSIONS: Postprandial glucose and protein absorption and gastro-entero-pancreatic hormone secretions differ after SG and RYGB. RYGB was characterized by accelerated absorption of glucose and amino acids, whereas protein metabolism after SG did not differ significantly from controls, suggesting that different mechanisms explain improved glycemic control and weight loss after these surgical procedures. ClinicalTrials.gov ID NCT03046186.

Plasma levels of guanylins are reduced in patients with Crohn's disease.

Background: Guanylin (GN) and uroguanylin (UGN) are endogenous ligands for the intestinal receptor guanylate cyclase C (GC-C), an important regulator of intestinal fluid homeostasis. Gene expression and protein levels of GN are suppressed in inflamed intestinal tissue from patients with inflammatory bowel disease (IBD), but knowledge about plasma levels of guanylins in these conditions is sparse. We aimed to investigate the fasting plasma levels of the prohormones proGN and proUGN in patients with Crohn's Disease (CD) and relate these to levels found in persons with other diarrheal conditions, as well as persons with normal bowel habits.Methods: Plasma from patients with CD, patients with Familial GUCY2C Diarrheal Disease (FGDS), diarrhea-predominant irritable bowel syndrome (IBS-D) and healthy controls (HC) was analyzed using ELISA assays.Results: Significantly lower fasting plasma levels of proguanylins were found in CD and FGDS patients, compared to HC. In CD patients, plasma proGN levels correlated negatively with Harvey Bradshaw Index and with number of stools/24 h.Conclusion: Our data indicate that diarrhea may be a determinant for levels of proGN in plasma, and should be further explored in studies of different diarrheal disorders.

Intraperitoneal Treatment of Kisspeptin Suppresses Appetite and Energy Expenditure and Alters Gastrointestinal Hormones in Mice.

BACKGROUND: Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus-pituitary-gonadal axis. Our current study explores for the first time the effects of a pharmacological treatment of intraperitoneal kisspeptin-10 on murine feeding behavior, respirometry parameters, energy balance, and metabolic hormones. METHODS: Two groups (n = 16) of age- and sex-matched C57BL/6 wild-type adult mice were individually housed in metabolic cages and intraperitoneally injected with either kisspeptin-10 (2 nmol in 200 µl of saline) (10 µM) or vehicle before the beginning of a dark-phase cycle. Microstructure of feeding and drinking behavior, respirometry gases, respiratory quotient (RQ), total energy expenditure (TEE), metabolic hormones, oral glucose tolerance, and lipid profiles were measured. RESULTS: Intraperitoneal treatment with kisspeptin-10 caused a significant reduction in food intake, meal frequency, meal size, and eating rate. Kisspeptin-10 significantly decreased TEE during both the dark and light phase cycles, while also increasing the RQ during the dark-phase cycle. In addition, mice injected with kisspeptin-10 had significantly higher plasma levels of insulin (343.8 pg/ml vs. 106.4 pg/ml; p = 0.005), leptin (855.5 pg/ml vs. 173.1 pg/ml; p = 0.02), resistin (9411.1 pg/ml vs. 4116.5 pg/ml; p = 0.001), and HDL (147.6 mg/dl vs 97.1 mg/dl; p = 0.04). CONCLUSION: A pharmacological dose of kisspeptin-10 significantly altered metabolism by suppressing food intake, meal size, eating rate, and TEE while increasing the RQ. These changes were linked to increased levels of insulin, leptin, resistin, and HDL. The current results suggest that a peripheral kisspeptin treatment could alter metabolism and energy homeostasis by suppressing appetite, food intake, and fat accumulation.

Energy intake, gastrointestinal transit, and gut hormone release in response to oral triglycerides and fatty acids in men with and without severe obesity.

Dietary fat, and particularly fatty acids (FAs) from hydrolyzed triglycerides (TGs), reduces appetite, whereas paradoxically, a high-fat diet leads to excess calorie intake. We therefore hypothesized that the appetite-regulating effects of FAs are perturbed in obesity. Ten men with severe obesity [median body mass index (BMI) of 51.0 kg/m2 (range of 47.9-69.0)] and 10 men without obesity [BMI of 24.6 kg/m2 (range of 21.7-26.8)] were recruited for a double-blind randomized crossover study. On two occasions, participants were given isocaloric (2,660 kJ) and isovolemic (80 ml) loads of either oleic acid (long-chain FA) or olive oil (TG) containing radiolabeled lipid and water markers. Postload scintigraphy, blood sampling, and assessment of appetite were performed for 10 h, after which an ad libitum meal was served. Compared with olive oil, oleic acid slowed gastric mean emptying time (GMET) for lipids ( P < 0.001), accelerated orocoecal transit time (OCTT; P = 0.005), increased postload cholecystokinin section ( P < 0.001), and suppressed ad libitum energy intake ( P = 0.028) in men with severe obesity, and similar effects were seen in the nonobese group (no group × lipid interactions). However, independent of lipid loads, GMET and OCTT were slower (GMETlipid P = 0.046; GMETwater P = 0.003; OCTT P = 0.001), and basal and postload secretion of glucagon-like peptide-1 (GLP-1) was attenuated ( P = 0.045 and P = 0.048, respectively) in men with severe obesity compared with men without obesity. We conclude that the more potent appetite-regulating effects of oleic acid versus olive oil are unimpaired in men with severe obesity. However, regardless of lipid formulations, severe obesity is associated with slowed gastrointestinal transit and attenuated GLP-1 secretion. NEW & NOTEWORTHY Orally ingested fatty acids more efficiently reduce appetite and energy intake than triglycerides also in men with severe obesity. Men with severe obesity have delayed gastrointestinal transit and attenuated early gut hormone responses after an oral lipid load compared with men without obesity.

Biliopancreatic diversion with duodenal switch (BPD-DS) and single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) result in distinct post-prandial hormone profiles.

BACKGROUND/OBJECTIVE: Biliopancreatic diversion with duodenal switch (BPD-DS) is the most effective bariatric intervention to treat morbid obesity and related disorders. Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a new bariatric procedure devised with the purpose of simplifying the complexity of the BPD-DS technique while maintaining its efficacy. However, whether BPD-DS and SADI-S result in similar fasting and post-prandial hormone profiles has not yet been studied. Therefore, the purpose of this study was to assess and compare the hormone response to a standardized mixed meal in subjects operated with BPD-DS or SADI-S. SUBJECTS/METHODS: Subjects submitted to BPD-DS (n = 9) or SADI-S (n = 9) 1.5 years earlier on average, with no past nor current diabetes diagnosis underwent a liquid mixed-meal tolerance test (MMTT) to assess the baseline and post-prandial profile of glucose, enteropancreatic hormones and total bile acids. RESULTS: Fasting glucose, enteropancreatic hormones and total bile acids levels after BPD-DS and SADI-S were similar. After the MMTT, the response of subjects who underwent SADI-S was characterized by higher glucose (t = 30 min: p < 0.05; iAUC: 156.1 ± 46.2 vs. 103.4 ± 35.8 mmol/L × min, p = 0.02), GLP-1 (t = 30 min: p < 0.05; iAUC: 5388 ± 3010 vs. 2959.0 ± 2146 pmol/L × min, p = 0.02), glucagon (t = 30 min: p < 0.05; iAUC: 678.7 ± 295.2 vs. 376.9 ± 215.7 pmol/L × min, p = 0.02), insulin (t = 30 and 45 min: p < 0.05); and C-peptide levels (t = 30 and 45 min: p < 0.05), when compared to BPD-DS. CONCLUSIONS: The post-prandial hormone secretion profile after SADI-S is characterized by increased GLP-1, glucagon and insulin secretion, when compared to BPD-DS, which suggests the existence of different endocrine driven mechanisms leading to weight loss and metabolic improvement after the two procedures.

Changes in gut hormones, glycaemic response and symptoms after oesophagectomy.

BACKGROUND: Oesophagectomy is associated with reduced appetite, weight loss and postprandial hypoglycaemia, the pathophysiological basis of which remains largely unexplored. This study aimed to investigate changes in enteroendocrine function after oesophagectomy. METHODS: In this prospective study, 12 consecutive patients undergoing oesophagectomy were studied before and 10 days, 6, 12 and 52 weeks after surgery. Serial plasma total fasting ghrelin, and glucagon-like peptide 1 (GLP-1), insulin and glucose release following a standard 400-kcal mixed-meal stimulus were determined. CT body composition and anthropometry were assessed, and symptom scores calculated using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires. RESULTS: At 1 year, two of the 12 patients exhibited postprandial hypoglycaemia, with reductions in bodyweight (mean(s.e.m.) 17·1(3·2) per cent, P < 0·001), fat mass (21.5(2.5) kg versus 25.5(2.4) kg before surgery; P = 0·014), lean body mass (51.5(2.2) versus 54.0(1.8) kg respectively; P = 0·003) and insulin resistance (HOMA-IR: 0.84(0.17) versus 1.16(0.20); P = 0·022). Mean(s.e.m.) fasting ghrelin levels decreased from postoperative day 10, but had recovered by 1 year (preoperative: 621·5(71·7) pg/ml; 10 days: 415·1(59·80) pg/ml; 6 weeks: 309·0(42·0) pg/ml; 12 weeks: 415·8(52·1) pg/ml; 52 weeks: 547·4(83·2) pg/ml; P < 0·001) and did not predict weight loss (P = 0·198). Postprandial insulin increased progressively at 10 days, 6, 12 and 52 weeks (mean(s.e.m.) insulin AUC0-30 min : fold change 1·7(0·4), 2·0(0·4), 3·5(0·7) and 4·0(0·8) respectively; P = 0·001). Postprandial GLP-1 concentration increased from day 10 after surgery (P < 0·001), with a 3·3(1·8)-fold increase at 1 year (P < 0·001). Peak GLP-1 level was inversely associated with the postprandial glucose nadir (P = 0·041) and symptomatic neuroglycopenia (Sigstad score, P = 0·017, R2 = 0·45). GLP-1 AUC predicted loss of weight (P = 0·008, R2 = 0·52) and fat mass (P = 0·010, R2 = 0·64) at 1 year. CONCLUSION: Altered enteroendocrine physiology is associated with early satiety, weight loss and postprandial hypoglycaemia after oesophagectomy.

Gastrointestinal capacity, gut hormones and appetite change during rat pregnancy and lactation.

Pregnancy and lactation increase maternal appetite and adiposity, which in humans can lead to long-term body mass retention. Previous rat reproduction studies suggest that appetite-inhibiting gut hormone, peptide-YY (PYY), is elevated, despite hyperphagia also that gastrointestinal size increases. The present study characterised changes in orexigenic (appetite-stimulating) ghrelin and anorexigenic (appetite-inhibiting) PYY and glucagon-like peptide-1 (GLP-1), and gastrointestinal architecture during pregnancy and lactation, in matched fed and fasted plasma and gut tissue samples taken during the dark phase. Enteroendocrine cells were immunolabelled, and gut masses and lengths were measured. Fasted plasma ghrelin reduced during pregnancy: it was lowest by day 18, recovered to control values at parturition, then increased by the end of lactation. Ghrelin-immunoreactive stomach cells and stomach ghrelin concentrations were highest at birth, prior to the onset of lactation-associated hyperphagia. Plasma fed GLP-1 concentrations were elevated during pregnancy, and together with higher colon concentrations of PYY and GLP-1 during early lactation, they were associated with gastrointestinal tissue expansion, not satiety. Body mass increased during lactation, whereas white adipose tissue depots depleted. Extensive gut remodelling coincided with elevated colon concentrations of PYY and GLP-1. Modifications included stomach and caecum expansion, and duodenal, ascending and descending colon circumference increases, all peaking by day 10 of lactation; increased intestinal masses and lengths peaking at lactation day 10 for small intestine and lactation day 25 for large intestine. If these physical tissue increases persist post-partum, they could accelerate future nutrient assimilation and storage in dams, and may contribute to increased obesity risk.

Gut Hormone Responses to Mixed Meal Test in New-Onset Prediabetes/Diabetes After Acute Pancreatitis.

The study was aimed to investigate gut hormone responses to mixed meal test in individuals with new-onset prediabetes or diabetes after acute pancreatitis (cases) compared with healthy controls, and the effect of body fat parameters. A total of 29 cases and 29 age- and sex-matched healthy controls were recruited. All participants were given standard mixed meal drink and blood samples were collected to measure dipeptidyl peptidase IV, gastric inhibitory peptide, glucagon like peptide-1, insulin, oxyntomodulin, and peptide YY. Body fat parameters were measured using magnetic resonance imaging. Repeated measures and linear regression analyses were conducted in unadjusted and adjusted models. Gastric inhibitory peptide levels were significantly higher whereas oxyntomodulin levels were significantly lower in cases compared with controls in both the unadjusted (p<0.001 and p<0.001, respectively) and adjusted (p<0.001 and p<0.001, respectively) models. In cases, liver fat % contributed up to 13.4% (vs. 2.9% in controls) to variance in circulating levels of gastric inhibitory peptide whereas body mass index - up to 20.8% (vs. 9.9% in controls) in circulating levels of oxyntomodulin. New-onset prediabetes/diabetes after acute pancreatitis is characterised by increased levels of gastric inhibitory peptide and decreased levels of oxyntomodulin. Further, liver fat % and body mass index appear to be the body fat parameters that contribute most significantly to gastric inhibitory peptide and oxyntomodulin levels, respectively.

Usefulness of antidiabetic alpha-glucosidase inhibitors: a review on the timing of administration and effects on gut hormones.

Elevation of postprandial plasma glucose is correlated with an increase in cardiovascular events, and alpha-glucosidase inhibitors (αGIs) are effective at reducing postprandial glucose levels. In Japan, the αGIs acarbose, voglibose, and miglitol have been available since 1993, 1994, and 2006, respectively. Dipeptidyl peptidase-4 (DPP-4) inhibitors are also effective at reducing postprandial glucose levels, and they have been available in Japan since 2009. A combination therapy of αGI, miglitol, and the DPP-4 inhibitor, sitagliptin, is more effective at decreasing postprandial glucose levels than monotherapy with either miglitol or sitagliptin. Moreover, the combination therapy of miglitol and sitagliptin is more effective at increasing postprandial active glucagon-like peptide-1 (GLP-1) levels than monotherapy. Peptide YY (PYY) has appetite-suppressing and gastric-emptying effects similar to GLP-1. In healthy individuals, miglitol increases the postprandial total PYY; however, combination therapy of miglitol and vildagliptin does not change postprandial total PYY levels. αGIs are typically prescribed to be taken just before a meal, which can result in decreased drug adherence. Different patterns of αGI intake were examined, and the results showed that miglitol or acarbose administration after a meal is effective. The effects of taking miglitol dissolved in water during a meal appeared to be similar to that of taking miglitol as a tablet just before a meal. The long-term effects of taking miglitol dissolved in water should be evaluated in future studies. αGIs may be effective even when they are not taken before a meal, and a more flexible administration may improve drug adherence.

Relationships between Body Composition and Plasma Levels of Pancreatic, Gut, and Adipose Tissue Hormones in db/db Mice, a Model of Type 2 Diabetes Mellitus.

We studied the relationships between body composition parameters and plasma levels of pancreatic, gut, and adipose tissue hormones regulating energy balance and glucose metabolism in diabetic db/db mice (BKS.Cg-Dock7m+/+Leprdb/J). The body composition parameters in mice aged 8, 12, and 16 weeks were assessed by magnetic resonance imaging. The concentrations of insulin, glucagon, ghrelin, glucagon-like peptide-1, glucose-dependent immunotropic peptide, leptin, resistin, and plasminogen activator-1 were measured by multiplex analysis at the age of 8 and 16 weeks. In comparison with non-diabetic control (db/+), db/db mice demonstrated high fat mass and reduced lean body mass and water content. In 8- and 16-week-old db/db mice, the levels of leptin (p<0.001), insulin (p<0.01), and glucagon-like peptide-1 (p<0.05) were elevated and the concentration of ghrelin (p<0.05) was reduced. The body weight and fat mass positively correlated with the levels of leptin, insulin, plasminogen activator-1, and glucagon-like peptide-1 and negatively correlated with ghrelin concentration. The results provide further details for characteristics of db/db mice, a widely used model of obesity and type 2 diabetes mellitus.

Pro-inflammatory cytokines after an episode of acute pancreatitis: associations with fasting gut hormone profile.

INTRODUCTION: Pro-inflammatory cytokines, such as interleukin (IL)-6, tumour necrosis factor (TNF)α, and monocyte chemoattractant protein (MCP)-1, are often elevated in individuals after acute pancreatitis but what determines their levels is poorly understood. Gut hormones have emerged as possible modulators of inflammatory response. The aim was to investigate the associations between pro-inflammatory cytokines and a comprehensive panel of gut hormones after an episode of acute pancreatitis. MATERIALS AND METHODS: Fasting blood samples were collected to measure cytokines (IL-6, TNFα, and MCP-1) and gut hormones (cholecystokinin, gastric inhibitory peptide (GIP), ghrelin, glicentin, glucagon-like peptide-1, oxyntomodulin, peptide YY, secretin, and vasoactive intestinal peptide). A series of linear regression analyses was conducted and four statistical models were used to adjust for patient- and pancreatitis-related covariates. RESULTS: A total of 83 individuals were recruited. GIP and peptide YY were significantly (p < 0.001) associated with IL-6, TNFα, MCP-1, consistently in all the four models. Every 1 ng/mL change in GIP resulted in a 16.2, 3.2, and 50.8% increase in IL-6, TNFα, and MCP-1, respectively, in the most adjusted model. Every 1 ng/mL change in peptide YY resulted in a 7.0, 2.4, and 32.1% increase in IL-6, TNFα, and MCP-1, respectively, in the most adjusted model. GIP independently contributed 29.0-36.5% and peptide YY - 17.4-48.9% to circulating levels of the studied pro-inflammatory cytokines. The other seven studied gut hormones did not show consistently significant associations with pro-inflammatory cytokines. CONCLUSIONS: GIP and peptide YY appear to be involved in perpetuation of subclinical inflammation following an episode of acute pancreatitis, which is known to play an important role in the pathogenesis of blood glucose derangements. These findings advance the understanding of mechanisms underlying diabetes of the exocrine pancreas and have translational implications.