Key Spec Table
|Analytes Available||Species Reactivity||Key Applications||Detection Methods|
|Glucagon Like Peptide-1||H, M, R||ELISA||Fluorescent|
|Description||Glucagon Like Peptide-1 (Active) ELISA|
|Background Information||GLP-1 is secreted from gut endocrine cells in response to nutrient ingestion and plays multiple roles in metabolic homeostasis.|
|Standard Curve Range||
|Safety Information according to GHS|
|Storage and Shipping Information|
|Material Size||96-well plate|
|Protocol: Glucagon-Like Peptide-1 (Active) ELISA KIT - 96-Well Plate|
|Reference overview||Pub Med ID|
|Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans.|
Rune E. Kuhre , Fiona M. Gribble , Bolette Hartmann , Frank Reimann , Johanne A. Windeløv , Jens F. Rehfeld , Jens J. Holst
Am J Physiol Gastrointest Liver Physiol. 2014 Apr 1;306(7):G622-30. 2014
Abstract Nutrients often stimulate gut hormone secretion, but the effects of fructose are incompletely understood. We studied the effects of fructose on a number of gut hormones with particular focus on glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). In healthy humans, fructose intake caused a rise in blood glucose and plasma insulin and GLP-1, albeit to a lower degree than isocaloric glucose. Cholecystokinin secretion was stimulated similarly by both carbohydrates, but neither peptide YY3-36 nor glucagon secretion was affected by either treatment. Remarkably, while glucose potently stimulated GIP release, fructose was without effect. Similar patterns were found in the mouse and rat, with both fructose and glucose stimulating GLP-1 secretion, whereas only glucose caused GIP secretion. In GLUTag cells, a murine cell line used as model for L cells, fructose was metabolized and stimulated GLP-1 secretion dose-dependently (EC50 = 0.155 mM) by ATP-sensitive potassium channel closure and cell depolarization. Because fructose elicits GLP-1 secretion without simultaneous release of glucagonotropic GIP, the pathways underlying fructose-stimulated GLP-1 release might be useful targets for type 2 diabetes mellitus and obesity drug development
|Circulating Glucagon-Like Peptide-1 (Glp-1) Inhibits Eating In Male Rats By Acting In The Hindbrain And Without Inducing Avoidance|
Mukesh Punjabi, Myrtha Arnold, Elisabeth Rüttimann, Mariana Graber, Nori Geary, Gustavo Pacheco-López, and Wolfgang Langhans
Endocrinology. 2014 May;155(5):1690-9. 2014
Abstract To address the neural mediation of the eating-inhibitory effect of circulating glucagon-like peptide-1 (GLP-1), we investigated the effects of 1) intra-fourth ventricular infusion of the GLP-1 receptor antagonist exendin-9 or 2) area postrema lesion on the eating-inhibitory effect of intrameal hepatic portal vein (HPV) GLP-1 infusion in adult male rats. To evaluate the physiological relevance of the observed effect we examined 3) the influence ofGLP-1 on flavor acceptance in a 2-bottle conditioned flavor avoidance test, and 4) measured active GLP-1 in the HPV and vena cava (VC) in relation to a meal and in the VC after HPV GLP-1 infusion. Intrameal HPV GLP-1 infusion (1 nmol/kg body weight-5 min) specifically reduced ongoing meal size by almost 40% (P < .05). Intra-fourth ventricular exendin-9 (10 ìg/rat) itself did not affect eating, but attenuated (P < .05) the satiating effect of HPVGLP-1. Area postrema lesion also blocked (P < .05) the eating-inhibitory effect of HPV GLP-1. Pairing consumption of flavored saccharin solutions with HPV GLP-1 infusion did not alter flavor acceptance, indicating that HPV GLP-1 can inhibit eating without inducing malaise. A regular chow meal transiently increased (P < .05) HPV, but not VC, plasma active GLP-1 levels, whereas HPV GLP-1 infusion caused a transient supraphysiological increase (P < .01) in VC GLP-1 concentration 3 minutes after infusion onset. The results implicate hindbrain GLP-1 receptors and the area postrema in the eating-inhibitory effect of circulating GLP-1, but question the physiological relevance of the eating-inhibitory effect of iv infused GLP-1 under our conditions.
|Glucagon-Like Peptide-1 Secretory Function As An Independent Determinant Of Blood Pressure: Analysis In The Tanno-Sobetsu Study|
Mayumi Yoshihara, Hiroshi Akasaka, Hirofumi Ohnishi, Takayuki Miki, Tetsuaki Furukawa, Satoshi Yuda, Shigeyuki Saitoh, Tetsuji Miura
PLoS One. 2013 Jul 2;8(7):e67578. doi: 10.1371/journal.pone.0067578. 2013
Abstract AIMS: Roles of glucagon-like peptide-1 (GLP-1) in extra-pancreatic tissues remain unclear. The aim of this study was to examine determinants of GLP-1 secretory function and possible contribution of GLP-1 to blood pressure (BP) regulation. METHODS AND RESULTS: We recruited 128 subjects who received annual examinations and 75g-oral glucose tolerance tests (OGTT) in the Tanno-Sobetsu cohort. Subjects on regular medications for cardiovascular and/or metabolic diseases were excluded, and data for the remaining 103 subjects were used for the univariate and multivariate analyses. Age, plasma glucose (PG), hemoglobin A1c (HbA1c), plasma insulin, and serum lipids were not selected as independent determinants of fasting GLP-1 level by multiple linear regression analysis. However, age and female sex were selected as independent positive determinants of the area under the curve of GLP-1 level during OGTT (AUCGLP-1), an index of GLP-1 secretoryfunction. Multiple linear regression analysis indicated that AUCGLP-1 was an independent negative predictor of systolic BP (SBP), while AUCGLP-1 was not correlated with fasting PG or HbA1c level. In subgroup analyses using the median of AUCGLP-1 to divide the study subjects into high and low GLP-1 response groups, AUCGLP-1 was significantly correlated with both SBP and diastolic BP (r = 0.40 and 0.28, respectively) in the low GLP-1 response group but not in the high GLP-1 response group. CONCLUSIONS: The results of the present study suggest that GLP-1 secretory function is involved in prevention of BP elevation and that the GLP-1 response to oral glucose rather increases with aging perhaps as an adaptive phenomenon.
|Evidence For Paracrine/Autocrine Regulation Of Glp-1-Producing Cells|
Camilla Kappe , Qimin Zhang , Jens J. Holst , Thomas Nyström , Åke Sjöholm
Am J Physiol Cell Physiol. 2013 Nov 15;305(10):C1041-9. 2013
Abstract Glucagon-like peptide-1 (GLP-1), secreted from gut L cells upon nutrient intake, forms the basis for novel drugs against type 2 diabetes (T2D). Secretion of GLP-1 has been suggested to be impaired in T2D and in conditions associated with hyperlipidemia and insulin resistance. Further, recent studies support lipotoxicity of GLP-1-producing cells in vitro. However, little is known about the regulation of L-cell viability/function, the effects of insulin signaling, or the potential effects of stable GLP-1 analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors. We determined effects of insulin as well as possible autocrine action of GLP-1 on viability/apoptosis of GLP-1-secreting cells in the presence/absence of palmitate, while also assessing direct effects on function. The studies were performed using the GLP-1-secreting cell line GLUTag, and palmitate was used to simulate hyperlipidemia. Our results show that palmitate induced production of reactive oxygen species and caspase-3 activity and reduced cell viability are significantly attenuated by preincubation with insulin/exendin-4. The indicated lipoprotective effect of insulin/exendin-4 was not detectable in the presence of the GLP-1 receptor (GLP-1R) antagonist exendin (9-39) and attenuated in response to pharmacological inhibition of exchange protein activated by cAMP (Epac) signaling, while protein kinase A inhibition had no significant effect. Insulin/exendin-4 also significantly stimulate acute and long-term GLP-1 secretion in the presence of glucose, suggesting novel beneficial effects of insulin signaling and GLP-1R activation on glycemia through enhanced mass of GLP-1-producing cells and enhanced GLP-1 secretion. In addition, the effects of insulin indicate that not only is GLP-1 important for insulin secretion but altered insulin signaling may contribute to an altered GLP-1 secretion.
|Effects Of Sleep Fragmentation On Appetite And Related Hormone Concentrations Over 24 H In Healthy Men|
Hanne K. J. Gonnissen, Rick Hursel, Femke Rutters, Eveline A. P. Martens and Margriet S. Westerterp-Plantenga
Br J Nutr. 2013 Feb 28;109(4):748-56. 2013
Abstract In addition to short sleep duration, reduced sleep quality is also associated with appetite control. The present study examined the effect of sleepfragmentation, independent of sleep duration, on appetite profiles and 24 h profiles of hormones involved in energy balance regulation. A total of twelvehealthy male subjects (age 23 (sd 4) years, BMI 24·4 (sd 1·9) kg/m²) completed a 24 h randomised crossover study in which sleep (23.30-07.30 hours) was either fragmented or non-fragmented. Polysomnography was used to determine rapid-eye movement (REM) sleep, slow-wave sleep (SWS) and total sleep time (TST). Blood samples were taken at baseline and continued hourly for the 24 h period to measure glucose, insulin, ghrelin, leptin, glucagon-like peptide 1 (GLP-1) and melatonin concentrations. In addition, salivary cortisol levels were measured. Visual analogue scales were used to score appetite-related feelings. Sleep fragmentation resulted in reduced REM sleep (69·4 min compared with 83·5 min; P< 0·05) and preservation of SWS without changes in TST. In fragmented v. non-fragmented sleep, glucose concentrations did not change, while insulin secretion was decreased in the morning, and increased in the afternoon (P< 0·05), and GLP-1 concentrations and fullness scores were lower (P< 0·05). After dinner, desire-to-eat ratings were higher after fragmented sleep (P< 0·05). A single night of fragmented sleep, resulting in reduced REM sleep, induced a shift in insulinconcentrations, from being lower in the morning and higher in the afternoon, while GLP-1 concentrations and fullness scores were decreased. These results may lead to increased food intake and snacking, thus contributing to a positive energy balance.
|Meal-contingent intestinal lymph sampling from awake, unrestrained rats.|
Myrtha Arnold,Yunting Dai,Patrick Tso,Wolfgang Langhans
American journal of physiology. Regulatory, integrative and comparative physiology 302 2012
Standard procedures for intestinal lymph collection involve continuous, quantitative drainage of the lymph fluid in anesthetized or restrained animals that are often euthanized within 48 h. We here describe a novel technique for the nonocclusive cannulation of the major intestinal lymph duct in rats that allows for repetitive in vivo sampling of intestinal lymph from unrestrained, awake, and ad libitum-fed animals. The distinctive feature of this novel technique is that a 5- to 7-mm long piece of Vialon tubing (OD/ID: 0.8/0.7 mm) with a small hole in its wall is first implanted into the major intestinal lymph duct for stabilization. The tapered tip (OD: ≈0.1 mm) of the catheter is then inserted into the hole of the tubing and fixed in place with a polyamid suture and a drop of tissue glue. In our hands, catheters implanted this way remain patent for up to 6 wk after surgery. In an initial experiment we collected lymph from six adult rats before (0) and 15, 30, 45, 60, 75, 90, 120, and 180 min (120 μl, each) after the onset of isocaloric (12.5 kcal) low-fat (LF) or high-fat (HF) test meals and measured active glucagon-like peptide-1 (GLP-1). Intestinal lymphatic GLP-1 concentration increased (P < 0.05) from ≈4 pmol/l (0 min) to a peak of 33 ± 6 (means ± SE) or 22 ± 4 pmol/l at 15 (HF) or 30 min (LF) after meal onset and gradually returned to baseline levels by 180 min. With this new technique fewer animals are required to generate physiologically relevant data for various aspects of gastrointestinal physiology that involve the lymphatic system. Furthermore, the advantage of this system is that the animal can act as its own control when the effect of different experimental protocols is tested.
|GLP-1 Receptor Antagonist Exendin-(9-39) Elevates Fasting Blood Glucose Levels in Congenital Hyperinsulinism Owing to Inactivating Mutations in the ATP-Sensitive K+ Channel.|
Andrew C Calabria,Changhong Li,Paul R Gallagher,Charles A Stanley,Diva D De Le
Diabetes 61 2012
Infants with congenital hyperinsulinism owing to inactivating mutations in the K(ATP) channel (K(ATP)HI) who are unresponsive to medical therapy will require pancreatectomy to control the hypoglycemia. In preclinical studies, we showed that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion and corrects fasting hypoglycemia in SUR-1(-/-) mice. The aim of this study was to examine the effects of exendin-(9-39) on fasting blood glucose in subjects with K(ATP)HI. This was a randomized, open-label, two-period crossover pilot clinical study. Nine subjects with K(ATP)HI received either exendin-(9-39) or vehicle on two different days. The primary outcome was blood glucose; secondary outcomes were insulin, glucagon, and GLP-1. In all subjects, mean nadir blood glucose and glucose area under the curve were significantly increased by exendin-(9-39). Insulin-to-glucose ratios were significantly lower during exendin-(9-39) infusion compared with vehicle. Fasting glucagon and intact GLP-1 were not affected by treatment. In addition, exendin-(9-39) significantly inhibited amino acid-stimulated insulin secretion in pancreatic islets isolated from neonates with K(ATP)HI. Our findings have two important implications: 1) GLP-1 and its receptor play a role in the regulation of fasting glycemia in K(ATP)HI; and 2) the GLP-1 receptor may be a therapeutic target for the treatment of children with K(ATP)HI.
|Rectal taurocholate increases L cell and insulin secretion, and decreases blood glucose and food intake in obese type 2 diabetic volunteers.|
T E Adrian,S Gariballa,K A Parekh,S A Thomas,H Saadi,J Al Kaabi,N Nagelkerke,B Gedulin,A A Young
Diabetologia 55 2012
Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are secreted from enteroendocrine L cells in response to numerous stimuli, including bile salts. Both have multiple effects that are potentially useful in treating diabetes and obesity. L cell number and hormone content in the intestine are highest in the rectum in humans. We investigated the effects of intrarectal sodium taurocholate on plasma GLP-1, PYY, insulin and glucose concentrations, and on food intake of a subsequent meal.
|Regular consumption of pulses for 8 weeks reduces metabolic syndrome risk factors in overweight and obese adults.|
R C Mollard,B L Luhovyy,S Panahi,M Nunez,A Hanley,G H Anderson
The British journal of nutrition 108 Suppl 1 2012
Pulses are low in energy density, supporting their inclusion in the diet for the management of risk factors of the metabolic syndrome (MetSyn). The aim of the present study was to describe the effects of frequent consumption (five cups/week over 8 weeks) of pulses (yellow peas, chickpeas, navy beans and lentils), compared with counselling to reduce energy intake by 2093 kJ/d (500 kcal/d), on risk factors of the MetSyn in two groups (nineteen and twenty-one subjects, respectively) of overweight or obese (mean BMI 32·8 kg/m2) adults. Body weight, waist circumference, blood pressure, fasting blood parameters and 24 h food intakes were measured at weeks 1, 4 and 8. Blood glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and ghrelin were measured after a 75 g oral glucose load at weeks 1 and 8. At week 8, both groups reported reductions in energy intake, waist circumference, systolic blood pressure, glycosylated Hb (HbA1c) and glucose AUC and homeostasis model of insulin resistance (HOMA-IR) following the glucose load (P < 0·05). However, HDL, fasting C-peptide and insulin AUC responses were dependent on diet (P < 0·05). HDL and C-peptide increased by 4·5 and 12·3 %, respectively, in the pulse group, but decreased by 0·8 and 7·6 %, respectively, in the energy-restricted group. Insulin AUC decreased in both females and males on the energy-restricted diet by 24·2 and 4·8 %, respectively, but on the pulse diet it decreased by 13·9 % in females and increased by 27·3 % in males (P < 0·05). In conclusion, frequent consumption of pulses in an ad libitum diet reduced risk factors of the MetSyn and these effects were equivalent, and in some instances stronger, than counselling for dietary energy reduction.
|Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus.|
Magnus Hillman,Leif Eriksson,Lena Mared,Karin Helgesson,Mona Landin-Olsson
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 11 2012
Glucagon like peptide 1 (GLP-1) is an incretin hormone released as a bioactive peptide from intestinal L-cells in response to eating. It acts on target cells and exerts several functions as stimulating insulin and inhibiting glucagon. It is quickly deactivated by the serine protease dipeptidyl peptidase IV (DPP-IV) as an important regulatory mechanism. GLP-1 analogues are used as antidiabetic drugs in patients with type 2 diabetes. We served patients with cystic fibrosis (CF, n=29), cystic fibrosis related diabetes (CFRD, n=19) and healthy controls (n=18) a standardized breakfast (23 g protein, 25 g fat and 76 g carbohydrates) after an overnight fasting. Blood samples were collected before meal as well as 15, 30, 45 and 60 min after the meal in tubes prefilled with a DPP-IV inhibitor. The aim of the study was to compare levels of GLP-1 in patients with CF, CFRD and in healthy controls. We found that active GLP-1 was significantly decreased in patients with CF and CFRD compared to in healthy controls (p<0.01). However, levels in patients with CFRD tended to be lower but were not significantly lower than in patients with CF without diabetes (p=0.06). Total GLP-1 did not differ between the groups, which points to that the inactive form of GLP-1 is more pronounced in CF patients. The endogenous insulin production (measured by C-peptide) was significantly lower in patients with CFRD as expected. However, levels in non-diabetic CF patients did not differ from the controls. We suggest that the decreased levels of GLP-1 could affect the progression toward CFRD and that more studies need to be performed in order to evaluate a possible treatment with GLP-1 analogues in CF-patients.
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