Postprandial Glucagon-like Peptide-1 Levels Research Articles

Impacts of different pancreatic resection ranges on endocrine function in Suncus murinus.

Surgical intervention involving the pancreas can lead to impaired glucose tolerance and other types of endocrine dysfunction. The scope of pancreatectomy and whether it includes the ventral pancreas are the key factors in the development of postoperative diabetes. The ventral and dorsal pancreases are almost separated in Suncus murinus (S. murinus). To investigate the effects of different extents of pancreatic resection on endocrine function in S. murinus. Eight-week-old male S. murinus shrews were randomly divided into three experimental groups according to different pancreatic resection ranges as follows: ventral pancreatectomy (VPx) group; partial pancreatectomy (PPx) group; subtotal pancreatectomy (SPx) group; and a sham-operated group. Postprandial serum insulin, glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and somatostatin (SST) levels, as well as food intake, weight, blood glucose, and glucose tolerance were regularly measured for each animal. S. murinus treated with PPx and SPx suffered from varying degrees of impaired glucose tolerance, but only a small proportion of the SPx group developed diabetes. Only S. murinus in the SPx group showed a significant decrease in food intake accompanied by severe weight loss, as well as a significant increase in postprandial serum GLP-1 levels. Postprandial serum PP levels decreased in both the VPx and PPx groups, but not in the SPx group. Postprandial serum SST levels decreased in both VPx and PPx groups, but the decrease was marginal. Severe weight loss after pancreatectomy may be related to loss of appetite caused by compensatory elevation of GLP-1. PP and GLP-1 may play a role in resisting blood glucose imbalance.

EFFECTS OF CHEWING TIME OF HIGH PROTEIN MEAL ON SATIETY AND GLP-1 HORMONE

Background: Chewing or mastication process affects satiety as well as satiety regulating hormone Glucagon-like Peptide-1 (GLP-1). Proteins have the highest satiating effects among the macronutrients. This study explored the association of chewing with satiety and GLP-1 in participants consuming high-protein meal. Methods: Fifteen healthy volunteers, aged 25-35 years were enrolled through random sampling. Effects of chewing on postprandial satiety and plasma GLP-1 was examined through quasi-experimental study conducted in Khyber Medical University, Peshawar, from Jan to Mar 2023. Three visits were designed with one week wash-out period. Satiety and GLP-1 were compared among normal, fast, and slow chewing conditions, while providing high protein meal. Subjective satiety was assessed via visual analogue scale (VAS) and labelled magnitude scale (LMS), while serum GLP-1 levels were analysed through ELISA at baseline, 30, 120 and 240 min in each visit. Results: The participants had a mean chewing time of 793.66±311 second at normal rate. Mean chewing time was decreased to 496.60±135.82 second during fast chewing, while significantly increased to 1459.66±400.83 second during slow chewing. A comparison of satiety at different chewing rates revealed that slow chewing significantly reduced hunger and enhanced fullness (p<0.05), relative to normal and fast chewing, at 240 minutes (p<0.05). However, no significant difference was observed in plasma GLP-1 levels at any time intervals (p>0.05). Conclusion: Satiety is significantly influenced by chewing and number of chews per bite of a high protein meal, whereas postprandial plasma GLP-1 levels show no significant differences across different chewing rates. Pak J Physiol 2024;20(2):31-35

Post metabolic bariatric surgery weight regain: the importance of GLP-1 levels.

Weight regain and insufficient weight loss are essential problems after metabolic bariatric surgery (MBS) in people living with obesity. Changes in the level of glucagon-like peptide-1 (GLP-1) secreted from the gut after bariatric surgery are one of the underlying mechanisms for successful initial weight loss. Studies and meta-analyses have revealed that postprandial GLP-1 levels increase after the Roux-en-Y gastric bypass and sleeve gastrectomy, but fasting GLP-1 levels do not increase significantly. Some observational studies have shown the relationship between higher postprandial GLP-1 levels and successful weight loss after bariatric surgery. There is growing evidence that GLP-1-receptor agonist (GLP-1-RA) use in patients who regained weight after bariatric surgery has resulted in significant weight loss. In this review, we aimed to summarize the changes in endogenous GLP-1 levels and their association with weight loss after MBS, describe the effects of GLP-1-RA use on weight loss after MBS, and emphasize metabolic adaptations in light of the recent literature. We hypothesized that maintaining higher basal-bolus GLP-1-RA levels may be a promising treatment choice in people with obesity who failed to lose weight after bariatric surgery.

Characterization of Postprandial Bile Acid Profiles and Glucose Metabolism in Cerebrotendinous Xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare inherited disease characterized by sterol 27-hydroxylase (CYP27A1) deficiency and, thus, a lack of bile acid synthesis with a marked accumulation of 7α-hydroxylated bile acid precursors. In addition to their renowned lipid-emulgating role, bile acids have been shown to stimulate secretion of the glucose-lowering and satiety-promoting gut hormone glucagon-like peptide 1 (GLP-1). In this paper, we examined postprandial bile acid, glucose, insulin, GLP-1 and fibroblast growth factor 19 (FGF19) plasma profiles in patients with CTX and matched healthy controls. Seven patients and seven age, gender and body mass index matched controls were included and subjected to a 4 h mixed meal test with regular blood sampling. CTX patients withdrew from chenodeoxycholic acid (CDCA) and statin therapy three weeks prior to the test. Postprandial levels of total bile acids were significantly lower in CTX patients and consisted of residual CDCA with low amounts of ursodeoxycholic acid (UDCA). The postprandial plasma glucose peak concentration occurred later in CTX patients compared to controls, and patients' insulin levels remained elevated for a longer time. Postprandial GLP-1 levels were slightly higher in CTX subjects whereas postprandial FGF19 levels were lower in CTX subjects. This novel characterization of CTX patients reveals very low circulating bile acid levels and FGF19 levels, aberrant postprandial glucose and insulin profiles, and elevated postprandial GLP-1 responses.

Influence of ursodeoxycholic acid on blood glucose, insulin and GLP-1 in rats with liver fibrosis induced by bile duct ligation

BackgroundThe prevalence of impaired glucose tolerance and diabetes is much higher in people with cirrhosis than that in the general population. However, there are inadequate concrete guidelines for the management of diabetes in these patients, particularly in the early stage. Bile aids (BAs) have been found to exert hormone-like functions in the control of lipid and glucose metabolism. We studied the effect of ursodeoxycholic acid (UDCA) on glucose levels in rats with cirrhosis induced by bile duct ligation (BDL).MethodsSD rats were divided into three groups: sham operation (Group A); BDL (Group B), and UDCA plus BDL (Group C). After 4 weeks, oral glucose tolerance tests were performed. Serum biochemical parameters and the levels of glucose, insulin, and glucagon-like peptide 1 (GLP-1) were measured. Histopathology of the liver and islet was observed. The gene expression of cholesterol 7α-hydroylase (CYP7A1), microsomal oxysterol 7a-hydroxylase (CYP7B1) in the liver, and Takeda G-protein-coupled receptor-5 (TGR5) in the intestine was determined by real-time PCR.ResultsCompared with Group A, fasting glucose and 1-h and 2-h postprandial glucose levels increased slightly (all P > 0.05), 2-h postprandial insulin levels increased significantly (P < 0.05), 15 min postprandial GLP-1 levels decreased (P < 0.05) in Group B. Compared with Group B, fasting glucose and 1-h postprandial glucose levels decreased (all P < 0.05), 2-h postprandial insulin levels decreased (P < 0.01), and 15 min postprandial GLP-1 levels increased (P < 0.05) in Group C. After UDCA intervention, liver fibrosis induced by BDL was alleviated, and the islet areas were increased (P < 0.05). Compared with Group A, the mRNA expression of CYP7A1 and CYP7B1 in the liver increased, and the mRNA expression of TGR5 in the intestine decreased in Group B (all P < 0.05). Compared with Group B, the mRNA expression of CYP7A1 and CYP7B1 in the liver decreased, and TGR5 in the intestine increased in Group C (P < 0.05).ConclusionsAfter 4 weeks of BDL, the rats developed liver fibrosis and abnormal glucose metabolism. UDCA administration improved liver fibrosis, increased islet area, decreased glucose levels, inhibited genes in BA synthesis, enhanced TGR5 gene expression in the intestine, and further improved islet function.

Effects of whole grain intake on glucagon-like peptide 1 and glucose-dependent insulinotropic peptide: a systematic review and meta-analysis.

Whole grain intake may control help glycemia and reduce food intake by affecting the secretion of glucagon-like peptide1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). This systematic review and meta-analysis aimed to assess the postprandial and long-term effects of whole grains on GLP-1 and GIP levels. PubMed, Web of Science, and Scopus online databases were searched systematically to identify relevant randomized clinical trials (RCTs) published up to April 2021. RCTs that evaluated the effects of whole grains, compared with refined grains, on the postprandial area under the curve (AUC) value, the postprandial serum concentration of incretins from 0 to 180 minutes, or the fasting level of incretins after at least 14 days of intervention were included. Nineteen studies were included in the meta-analysis. The results showed that acute intake of whole grains could not significantly change the AUC value of GLP-1 or GIP. However, the AUC value of GIP was reduced more significantly in (1) unhealthy participants (standard mean difference [SMD] -1.08; 95%CI, -2.07 to -0.10; I2 = 75.9%) compared with healthy participants, and (2) those with a baseline fasting blood glucose of ≥99 mg/dL (SMD -0.71; 95%CI, -1.30 to -0.11; I2 = 74.4%) compared with those with a baseline value of < 99 mg/dL. On the other hand, the results of time-response evaluation during 0 to 180 minutes after the intake of test meals showed that serum concentrations of GIP decreased significantly from 0 to 30 minutes (coefficient = -44.72; P = 0.005), but increased from 60 to 180 minutes (coefficient = 27.03; P = 0.005). However, long-term studies found no significant effects of whole grains on fasting concentrations of GLP-1 or GIP. Whole grain intake did not affect postprandial levels of GLP-1 but enhanced postprandial levels of GIP from 60 to 180 minutes. Further high-quality trials are required to assess the long-term effects of whole grain intake on serum levels of incretins. PROSPERO registration no. CRD42021256695.

Incretin Hypersecretion in Gestational Diabetes Mellitus.

Incretins are crucial stimulators of insulin secretion following food intake. Data on incretin secretion and action during pregnancy are sparse. The aim of the study was to investigate the incretin response during an oral glucose tolerance test (OGTT) in pregnant women with and without gestational diabetes mellitus (GDM). We analyzed data from the ongoing observational PREG study (NCT04270578). The study was conducted at the University Hospital Tübingen. We examined 167 women (33 with GDM) during gestational week 27 ± 2.2. Subjects underwent 5-point OGTT with a 75-g glucose load. We assessed insulin secretion and levels of total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), glicentin, and glucagon during OGTT. Linear regression was used to analyze the relation of GLP-1 and glucose with insulin secretion and the association of incretin levels on birth outcome. Insulin secretion was significantly lower in women with GDM (P < 0.001). Postload GLP-1 and GIP were ~20% higher in women with GDM (all P < 0.05) independent of age, body mass index, and gestational age. GLP-1 increase was associated with insulin secretion only in GDM, but not in normal glucose tolerance. Postprandial GLP-1 levels were negatively associated with birth weight. The more pronounced GLP-1 increase in women with GDM could be part of a compensatory mechanism counteracting GLP-1 resistance. Higher GLP-1 levels might be protective against fetal overgrowth.

Rise in Postprandial GLP-1 Levels After Roux-en-Y Gastric Bypass: Involvement of the Vagus Nerve-Spleen Anti-inflammatory Axis in Type 2 Diabetic Rats.

The mechanism underlying postprandial glucagon-like peptide-1 (GLP-1) changes after metabolic surgery remains mostly unclarified. This investigation aimed to address whether the vagus nerve-spleen anti-inflammatory axis is involved in the rise in postprandial GLP-1 levels in type 2 diabetes mellitus (T2DM) rats following metabolic surgery. T2DM rat model was established with a high-fat diet and a low dose of streptozotocin and subjected to Roux-en-Y gastric bypass (RYGB) and splenic denervation. A mixed-meal tolerance test for postprandial GLP-1 response was performed. TNF-α in the plasma, spleen, and ileum was measured by ELISA, and alpha 7 nicotinic acetylcholine receptor (α7nAChR) expression in the spleen was analyzed by Western blot. Postprandial GLP-1 improvement by RYGB was accompanied by the reduction of TNF-α levels in spleen and ileum and up-regulation of splenic α7nAChR in T2DM rats. Splenic denervation abrogates a rise in postprandial GLP-1 levels in response to the mixed-meal challenge, along with higher TNF-α levels in spleen and ileum and down-regulation of splenicα7nAChR, compared with denervated sham rats. Our results reveal that the vagus nerve-spleen anti-inflammatory axis mediates the rise of postprandial GLP-1 response after RYGB through lowering TNF-α contents in the intestinal tissue in T2DM rats.

Targeting the Enteroendocrine System for Treatment of Obesity.

Mimetics of the anorexigenic gut hormone glucagon-like peptide 1 (GLP-1) were originally developed as insulinotropic anti-diabetic drugs but also evoke significant weight loss, leading to their recent approval as obesity therapeutics. Co-activation of receptors for GLP-1 and other gut hormones which reduce food intake - peptide YY (PYY3-36), cholecystokinin (CCK) and glucose-dependent insulinotropic peptide (GIP) - is now being explored clinically to enhance efficacy. An alternative approach involves pharmacologically stimulating endogenous secretion of these hormones from enteroendocrine cells (EECs) to recapitulate the metabolic consequences of bariatric surgery, where highly elevated postprandial levels of GLP-1 and PYY3-36 are thought to contribute to improved glycaemia and weight loss.

Plasma GLP-1 Response to Oral and Intraduodenal Nutrients in Health and Type 2 Diabetes-Impact on Gastric Emptying.

Both gastric emptying and the secretion of glucagon-like peptide-1 (GLP-1) are major determinants of postprandial glycemia in health and type 2 diabetes (T2D). GLP-1 secretion after a meal is dependent on the entry of nutrients into the small intestine, which, in turn, slows gastric emptying. To define the relationship between gastric emptying and the GLP-1 response to both oral and small intestinal nutrients in subjects with and without T2D. We evaluated: (i) the relationship between gastric emptying (breath test) and postprandial GLP-1 levels after a mashed potato meal in 73 individuals with T2D; (ii) inter-individual variations in GLP-1 response to (a) intraduodenal glucose (4 kcal/min) during euglycemia and hyperglycemia in 11 healthy and 12 T2D, subjects, (b) intraduodenal fat (2 kcal/min) in 15 T2D subjects, and (c) intraduodenal protein (3 kcal/min) in 10 healthy subjects; and (iii) the relationship between gastric emptying (breath test) of 75 g oral glucose and the GLP-1 response to intraduodenal glucose (4 kcal/min) in 21 subjects (9 healthy, 12 T2D). The GLP-1 response to the mashed potato meal was unrelated to the gastric half-emptying time (T50). The GLP-1 responses to intraduodenal glucose, fat, and protein varied substantially between individuals, but intra-individual variation to glucose was modest. The T50 of oral glucose was related directly to the GLP-1 response to intraduodenal glucose (r = 0.65, P = 0.002). In a given individual, gastric emptying is not a determinant of the postprandial GLP-1 response. However, the intrinsic gastric emptying rate is determined in part by the responsiveness of GLP-1 to intestinal nutrients.

Are the Changes in Gastrointestinal Hormone Secretion Necessary for the Success of Bariatric Surgery? A Critical Review of the Literature.

Ghrelin, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) are involved in energy balance regulation and glucose homeostasis. Obesity is characterized by lower fasting levels and blunted postprandial responses of ghrelin, GLP-1, and possibly PYY. Both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have been shown to increase postprandial GLP-1 and PYY levels. Human studies have shown that enhanced postprandial GLP-1 and PYY release are associated with favorable weight loss outcomes after RYGB. However, studies in knockout mice have shown that GI hormones are not required for the primary metabolic effects of bariatric surgery. Here, we summarize the complex interaction between obesity, bariatric surgery, and GI hormones in order to determine the exact role of GI hormones in the success of bariatric surgery.

Attenuated Postprandial GLP-1 Response in Parkinson's Disease.

The incretin hormone glucagon-like peptide 1 (GLP-1) has neuroprotective effects in animal models of Parkinson’s disease (PD), and GLP-1 receptor agonists are associated with clinical improvements in human PD patients. GLP-1 is produced and secreted by intestinal L-cells in response to consumption of a meal. Specifically, intestinal microbiota produce short chain fatty acids (SCFA) which, in turn, promote secretion of GLP-1 into the systemic circulation, from which it can enter the brain. Our group and others have reported that PD patients have an altered intestinal microbial community that produces less SCFA compared to age-matched controls. In this report, we demonstrate that PD patients have diminished GLP-1 secretion in response to a meal compared to their household controls. Peak postprandial GLP-1 levels did not correlate with PD disease severity, motor function, or disease duration. These data provide the scientific rationale for future studies designed to elucidate the role of GLP-1 in the pathogenesis of PD and test the potential utility of GLP-1-directed therapies.

Emodin Attenuated the Kidney Damage of High-Fat-Diet Mice via the Upregulation of Glucagon-Like Peptide-1 Receptor.

Objective Secretion of glucagon-like peptide 1 (GLP-1) and its effect on target organs were impaired in individuals with obesity. However, its mechanism needs to be further studied. We aim to explore the roles of the receptor of GLP-1 (GLP-1R) involved in high-fat-diet- (HFD-) induced kidney damage improved by emodin. Methods Male C57bl/6 mice were fed with HFD diet and therapied by emodin. NRK-52E cells were cultured and treated with palmitic acid or low-density lipoprotein cholesterol (LDL-C). Emodin was used to remedy the NRK-52E cell damage. GW9662 was administrated to block the function of peroxisome proliferator-activated receptor γ (PPAR-γ). GLP-1 in the plasma was measured by ELISA. PPAR-γ and GLP-1R in the kidney and NRK-52E cells were detected by western blotting. The interaction between PPAR-γ protein and GLP-1R promoter regions was observed by chromatin immunoprecipitation (ChIP). Results Postprandial GLP-1 levels in plasma, as well as PPAR-γ and GLP-1R, decreased in kidney tissue of HFD mice, while they were reserved by emodin treatment. Although PPAR-γ and GLP-1R were not downregulated by LDL-C, they were suppressed by palmitic acid. Interestingly, GLP-1R mRNA was detected by PCR in the mixture pulled down with PPAR-γ antibody. Additionally, downregulation of PPAR-γ and GLP-1R by palmitic acid was remanded by emodin. Moreover, GW9662, an inhibitor of PPAR-γ, abolished the protective effect of emodin. Conclusion The kidney damage of HFD mice seems to be alleviated by emodin via the upregulation of GLP-1R in kidney tissue.

516 UROCORTIN 3 EXPRESSION IN HUMAN ENTEROENDOCRINE CELLS AND CORRELATION WITH PLASMA GLP1 LEVELS IN HUMAN OBESITY

Introduction Enteroendocrine cells (EECs) are hormone secretory cells sparsely distributed throughout the GI tract, and implicated in obesity. Intestinal L-type EECs secrete Glucagon-Like peptide 1(GLP-1) in response to a meal to promote satiety and maintain glucose homeostasis. Abnormal post prandial satiety (APS) is a phenotypic subset of obesity characterized by blunted post-prandial levels of GLP-1. Intestinal D-type EECs release somatostatin (SST) to inhibit GLP-1 release from L cells via the STT-receptor. In the pancreas, somatostatin release from delta cell is stimulated by pancreatic urocortin-3 from the beta cells. It is unknown whether urocortin-3 is expressed in intestinal EEC cells. Thus, we aimed to study the role of UCN3 in intestinal L, and D- type EECs, and its association with GLP-1 secretion in human obesity. Methods We studied a total of 34 participants, 17 healthy controls (age 38±13y, BMI 23±2kg/m2, 59% female), and 17 with obesity (age 39±9y, BMI 37±5kg/m2, 65% female). Obesity was sub-grouped into: Abnormal postprandial satiety (APS, low postprandial GLP-1, n=6) and normal post prandial satiety (NPS, normal postprandial GLP-1, n=11). Human colonic biopsies from participants were obtained by sigmoidoscopy and preserved for scRNA-seq (CryoStorCS10), gene expression (RNAlater), or microscopy studies (10%NBF). Single-cell transcriptomics was completed using the Chromium 10X Genomics platform followed by Illumina HiSeq4000 sequencing. Blood was collected from participants at fasting, and postprandial at 15, 45, and 90 minutes. Immunofluorescence (IF) confocal microscopy was used to detect protein expression of UCN3 in L-type EECs in the gut mucosa. UCN3 mRNA expression was determined by RT-qPCR. Blood GLP-1 levels were determined by ELISA. Results Our transcriptomic investigation of EECs in human obesity revealed expression of UCN3 in Chromogranin A-positive EECs, and GLP-1 positive L-type EECs, previously not known to be expressed in EECs (Fig1A). Protein expression of UCN3 in GLP-1 positive EEC was confirmed using immunofluorescence in human ileum and colon (Fig 1B). Colonic UCN3 mRNA expression was positively associated with BMI (r=0.43, p Conclusions These findings suggest that intestinal UCN3 is overexpressed in obesity, and further overexpressed in APS obesity phenotype. This study introduces a new pathophysiological underpinning of obesity where negative feedback mechanisms of SST-mediated GLP-1 inhibition are exaggerated, and may potentially promote blunted postprandial GLP-1 levels and decreased satiety in obesity. Download : Download high-res image (100KB) Download : Download full-size image Figure 1 . Expression of Urocortin 3 (UCN3) in human enteroendocrine cells (EECs). (A) Ratio of cell population clusters of the human colonic mucosa in either all EECs or just GCG-expressing L-Type EECs, expressing UCN3 of 10 patients (n=4 lean, n=6 obesityall). (B) Double immunoflurescent staining of the human intestinal mucosa demonstrating expression of UCN3 (Red) in a subset of GLP-1 (Green) L-type EECs. Red bar indicates 20µm. Download : Download high-res image (95KB) Download : Download full-size image Figure 2 . Urocortin 3 (UCN3) Associations with BMI and GLP-1 Release. (A) Association of colonic UCN3 mRNA expression (A) to BMI (kg/m2). Relative Human colonic mucosal mRNA expression of UCN3 comparing (B) lean and all-obesity; and (C) lean and obesity with and without APS. Association of intestinal UCN3 expression with (D) plasma concentrations of GLP-1 measured 45 and (C) resulting association of GLP-1 area under the curve (AUC). Significance testing used a linear regression for A,D, E, and a two-tailed student t-test compared between all groupings; # p

Acute postprandial effect of yacon syrup ingestion on appetite: A double blind randomized crossover clinical trial

Yacon syrup is a rich source of fructooligosaccharides (FOS); however, its diet supplementation effect on subjective sensation and appetite biomarkers in human is still unknown. This study aimed to evaluate the acute postprandial effect of yacon syrup ingestion on appetite. The double-blind crossover clinical trial was carried out with 40 adult women: 20 eutrophic and 20 obese grade I. On each day, the first blood collection was performed after a 12-h fast. Then, the volunteers ingested either intervention A (breakfast + 40 g of placebo) or intervention B (breakfast + 40 g of yacon syrup, containing 14 g of FOS). New aliquots of blood were collected at 45, 60, 90, 120, and 180 min. Appetite was assessed by estimating ghrelin and glucagon-like peptide-1 (GLP-1) levels and by assessing subjective appetite sensation. Analysis was performed using two-way ANOVA, followed by Bonferroni's multiple comparison test. No effect of yacon syrup was observed on postprandial ghrelin and GLP-1 levels at all times evaluated. Similar observations were made after stratifying the analysis by BMI (body mass index) (eutrophic and obese). The effect of yacon syrup on postprandial subjective sensations of hunger, satiety, fullness, and desire to eat was not evident in the total group of women evaluated and even after BMI stratification. We concluded that yacon syrup had no effect on postprandial ghrelin and GLP-1 levels and on the subjective appetite sensation in young adult women.

Fasting Ghrelin and Postprandial GLP-1 Levels in Patients With Morbid Obesity and Medical Comorbidities After Sleeve Gastrectomy and One-anastomosis Gastric Bypass: A Randomized Clinical Trial

Sleeve gastrectomy (SG) and one-anastomosis gastric bypass (OAGB) are among the commonly performed bariatric procedures. This randomized study aimed to compare SG and OAGB in terms of weight loss, improvement in comorbidities, and change in serum ghrelin and glucagon-like peptide-1 (GLP-1) levels. This was a prospective randomized trial on patients with morbid obesity associated with medical comorbidities who were randomly assigned to 1 of 2 equal groups; group I underwent SG and group II underwent OAGB. Outcome measures were percent of excess weight loss (%EWL), improvement in comorbidities, change in the venous levels of fasting ghrelin and postprandial GLP-1 at 12 months after surgery, in addition to operation time and complications. Forty patients (38 female) of a mean age of 33.8 years and mean body mass index of 48.6 kg/m2 were included. Operation time in group II was significantly longer than in group I (86 vs. 52.87 min; P<0.001). There were 6 recorded complications (1 in group I and 5 in group II, P=0.18). The %EWL, %total weight loss, and %excess body mass index loss at 6 and 12 months postoperatively were significantly higher in group II than in group I. Both groups had similar rates of improvement in comorbidities. Group I had significantly lower ghrelin and GLP-1 levels postoperatively at 6 and 12 months, respectively, as compared with group II. OAGB was associated with significantly higher EWL than SG. The reduction in fasting ghrelin and postprandial GLP-1 serum levels at 12 months after SG was significantly higher than that after OAGB.

Supplementation with Low Doses of a Cod Protein Hydrolysate on Glucose Regulation and Lipid Metabolism in Adults with Metabolic Syndrome: A Randomized, Double-Blind Study

The risk of cardiovascular diseases and type 2 diabetes mellitus are increased in subjects with metabolic syndrome (MetS), and hydrolyzed fish protein may have favorable effects on metabolic health. Here, we investigated the effect of 8 weeks supplementation with 4 g of cod protein hydrolysate (CPH) on glucose metabolism, lipid profile and body composition in individuals with MetS in a double-blind, randomized intervention study with a parallel-group design. Subjects received a daily supplement of CPH (n = 15) or placebo (n = 15). Primary outcomes were serum fasting and postprandial glucose levels. Secondary outcomes were fasting and postprandial insulin and glucagon-like peptide 1 (GLP-1), fasting lipid concentrations and body composition. No difference was observed between CPH and placebo for insulin, glucose or GLP-1 after 8 weeks intervention. Fasting triacylglycerol decreased in both the CPH group and placebo group, with no change between groups. Fasting total cholesterol and low-density lipoprotein cholesterol decreased significantly within both groups from baseline to study end, but no difference was observed between the two groups. In conclusion, supplementing with a low dose of CPH in subjects with MetS for 8 weeks had no effect on fasting or postprandial levels of insulin, glucose or GLP-1, lipid profile or body composition.

GLP-1 Analog Modulates Appetite, Taste Preference, Gut Hormones, and Regional Body Fat Stores in Adults with Obesity.

Obesity is associated with alterations in appetite, gastrointestinal hormone levels and excessive fat mass. We previously published a double-blind, placebo-controlled, randomized, 16-week trial on effects of once-daily glucagon-like peptide-1 (GLP-1) analog, liraglutide on weight, satiation, and gastric functions in obese volunteers. The aim of this substudy is to compare to placebo the effects of liraglutide on appetite, taste preference, regional body fat stores, and anthropometric measurements. Forty obese adults received standard instruction for weight management, monthly behavioral intervention utilizing motivational interviews, and 16-week treatment of once-daily liraglutide (escalated to 3 mg SQ daily). At baseline and 16 weeks, the following were measured: appetite and taste preferences rated every 30 min for 5 h after ingesting 300 mL Ensure®; maximal tolerated volume (MTV) with a nutrient drink test; fasting and postprandial bioactive GLP-1 (7-36) and peptide YY (PYY) levels; total and regional body fat with dual-energy X-ray absorptiometry, and waist and hip circumference. Thirty-five participants (17 liraglutide; 18 placebo) completed the trial. Compared to placebo group, liraglutide group had significant reductions in MTV; prospective food consumption score; desire to eat something sweet, salty, savory or fatty; and an increase in perceived fullness. Postprandial plasma levels of GLP-1 decreased and PYY levels increased with liraglutide relative to baseline. Significant reductions in total body, trunk, and upper and lower body fat without reduction in lean body mass were observed. Liraglutide 3 mg SQ modulates appetite, taste preference, gut hormones, and regional body fat stores in adults with obesity without reduction in lean body mass.

Subjects with high fasting insulin also have higher postprandial GLP-1 and glucagon levels than controls with lower insulin

Little is known about postprandial release of serum ghrelin, glucagon, and glucagon-like peptide-1 (GLP-1) in relation with differing fasting insulin levels. We hypothesized that these hormones are affected by insulin resistance, and hence, we compared different postprandial responses of GLP-1, glucagon, and ghrelin in subjects with relatively high (RHI) or relatively low (RLI) fasting insulin levels. The trial was a randomized crossover study with 4 different meal conditions. Fourteen nonobese or obese, healthy, men and 14 women were randomly assigned to the order of supervised intake of a 750 kcal drink with the same protein contents but with 20 energy-percent (E%) or 55 E% from carbohydrates, and the remaining energy from fat. Participants were also randomized to consume the drinks as 1 large beverage or as five 150-kcal portions every 30 minutes. The 28 subjects were divided into 2 equally sized groups based on fasting insulin levels. Statistics were done with general linear mixed model. Fasting insulin levels were 3-fold higher in the group with RHI compared with the RLI group (RHI: 1004 ± 510 pg/mL, RLI: 324 ± 123 pg/mL, P < .0005). Serum GLP-1 was highest in the RHI group after both single meals and after 5 drinks and following high- and low-carbohydrate meals (both P ≤ .002), and this was the case also for glucagon levels (both P ≤ .018), whereas ghrelin levels did not differ between groups. Thus, subjects with RHI displayed both higher postprandial serum GLP-1 and glucagon than the participants with RLI, suggesting that glucagon could play a role in the advent of dysglycemia by insulin resistance.

Effect of Sleeve Gastrectomy on Ghrelin, GLP-1, PYY, and GIP Gut Hormones: A Systematic Review and Meta-analysis.

To perform a structured systematic review and meta-analysis to evaluate changes in ghrelin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and gastric inhibitory peptide (GIP) gut hormone levels in patients after sleeve gastrectomy. Despite sleeve gastrectomy becoming the most common surgical weight loss procedure, weight loss mechanisms remain less clear. Searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were performed through April 1, 2019, in accordance with PRISMA and MOOSE guidelines. Randomized controlled trials and prospective observational studies evaluating pre and post-procedure hormones fasting ghrelin, postprandial GLP-1, postprandial PYY, and fasting GIP levels were included. Hedge g with random-effects models were used to determine pooled effect size and corresponding 95% confidence intervals (CIs). A total of 28 studies (n = 653; 29.56% male) were included. Mean age was 42.00 ± 5.48 years, with average follow-up of 11.70 ± 11.38 months. Pre-procedure body mass index (BMI) was 46.01 ± 4.07 kg/m with a postsleeve gastrectomy BMI of 34.07 ± 3.73 kg/m, representing total body weight loss of 25.13 ± 4.44% and excess weight loss of 57.48 ± 9.64% (P < 0.001). Ghrelin decreased (Hedge g -1.486, 95% CI -1.884 to -1.089, I = 91.95%), whereas GLP-1 and PYY increased post-procedure (Hedge g 1.095, 95% CI 0.509 to 1.642, I = 84.38%; and Hedge g 1.396, 95% CI 0.781 to 2.011, I = 84.02%, respectively). GIP did not significantly change (Hedge g -0.213, 95% CI -1.019 to 0.592, I = 79.65%). Fasting ghrelin levels decreased, whereas postprandial GLP-1 and PYY increased after sleeve gastrectomy. Fasting GIP levels remained unchanged. Future studies are needed to assess the role of these gut hormones and relationship to weight loss and metabolic outcomes.