glucagon-like-peptide-1 and Anorexia-Nervosa

Dipeptidyl peptidase IV (DPPIV) is a protease with broad distribution involved in various homeostatic processes such as immune defense, psychoneuroendocrine functions and nutrition. While DPPIV protein levels were investigated in patients with hyporectic disorders, less is known under conditions of obesity. Therefore, we investigated DPPIV across a broad range of body mass index (BMI). Blood samples from hospitalized patients with normal weight (BMI 18.5-25 kg/m(2)), anorexia nervosa (BMI <17.5 kg/m(2)) and obesity (BMI 30-40, 40-50 and >50 kg/m(2), n = 15/group) were tested cross-sectionally and DPPIV concentration and total enzyme activity and the DPPIV targets, pancreatic polypeptide (PP) and glucagon-like peptide (GLP-1) were measured. DPPIV protein expression was detected in human plasma indicated by a strong band at the expected size of 110 kDa and another major band at 50 kDa, likely representing a fragment comprised of two heavy chains. Obese patients had higher DPPIV protein levels compared to normal weight and anorexics (+50%, p<0.05) resulting in a positive correlation with BMI (r = 0.34, p = 0.004). DPPIV serum activity was similar in all groups (p>0.05), while the concentration/activity ratio was higher in obese patients (p<0.05). Plasma PP levels were highest in anorexic patients (∼ 2-fold increase compared to other groups, p<0.05), whereas GLP-1 did not differ among groups (p<0.05). Taken together, circulating DPPIV protein levels depend on body weight with increased levels in obese resulting in an increased concentration/activity ratio. Since DPPIV deactivates food intake-inhibitory hormones like PP, an increased DPPIV concentration/activity ratio might contribute to reduced food intake-inhibitory signaling under conditions of obesity.

Topics: Anorexia Nervosa; Body Mass Index; Dipeptidyl Peptidase 4; Female; Gene Expression Regulation, Enzymologic; Glucagon-Like Peptide 1; Humans; Male; Obesity; Pancreatic Polypeptide; Signal Transduction

Entero-insular axis plays an important role in generating satiety signal. Thus disturbances in this axis may influence the course of anorexia nervosa. The aim of the study was analysis of the function of the hormonal part of the entero-insular axis in girls with anorexia nervosa. Thirteen girls with anorexia nervosa and in 10 healthy girls were studied. Each girl was subjected to oral glucose tolerance test and standard meal test. Blood was collected before stimulation and within 15, 30, 60, and 120 min thereafter. The concentrations of all peptides were determined by radioimmunoassay commercial kits. Fasted and postprandial levels of these peptides as well as integrated outputs were measured. Fasting insulin concentration was significantly higher in the group of girls with anorexia nervosa than in the control group (p<0.03). What more in girls with anorexia the integrated output of insulin was significantly lower in oral glucose tolerance test than after the meal (p<0.001). Also the integrated output of glucagon in both tests was higher in the group of girls with anorexia than in the control group. The mean output of pancreatic polypeptide and cholecystokinin in anorexia group was significantly higher (p<0.001 in both cases) than that in the control group but only after the test meal. The integrated outputs of gastric inhibitory peptide in both tests were significantly higher in anorectic girls than those in the control group (oral glucose tolerance test, p<0.02; meal test, p<0.001), However, mean values of the integrated output of glucagon-like peptide 1 in both tests were significantly higher in the control group than in the girls with anorexia (p<0.001 in each case). Highly significant correlation was found between glucose concentration and the concentrations of insulin, cholecystokinin, and gastric inhibitory peptide in both tests and for the both groups. In the anorectic girls, significant correlation between insulin concentration and the concentration of gastric inhibitory peptide was found after both stimulation tests and between insulin and cholecystokinin after oral glucose only.. the disturbed secretion of the hormones of entero-insular axis after the meal in anorectic girls may have negative influence on the course of anorexia nervosa. This disease has no effect on the incretin function of cholecystokinin, gastric inhibitory peptide and glucagon-like peptide 1.

Topics: Adolescent; Anorexia Nervosa; Blood Glucose; Cholecystokinin; Eating; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Intestines; Pancreatic Polypeptide; Peptide Fragments; Protein Precursors; Signal Transduction

Postprandial glucose is reduced in malnourished patients with anorexia nervosa (AN), but the mechanisms and duration for this remain unclear. We examined blood glucose, gastric emptying, and glucoregulatory hormone changes in malnourished patients with AN and during 2 wk of acute refeeding compared with healthy controls (HCs). Twenty-two female adolescents with AN and 17 age-matched female HCs were assessed after a 4-h fast. Patients were commenced on a refeeding protocol of 2,400 kcal/day. Gastric emptying (

Topics: 3-O-Methylglucose; Adolescent; Anorexia Nervosa; Blood Glucose; Breath Tests; C-Peptide; Caprylates; Carbon Isotopes; Case-Control Studies; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Postprandial Period; Starvation; Young Adult

Food intake is controlled by the arcuate nucleus through integration of peripheral hormonal signals such as leptin, ghrelin, peptide YY (PYY), and glucagon-like peptide 1 (GLP-1). The most common condition resulting in underweight young women in the developed world is restrictive anorexia nervosa (AN). However, constitutional thinness (CT) is also known to exist in the same low-weight range. Women with CT have normal menstrual periods and do not have the psychological or hormonal features of AN. Little is currently known about regulation of food intake in subjects with CT.. We tested the hypothesis that concentrations of leptin, ghrelin, PYY, and GLP-1 in persons with AN are significantly different from those in persons with CT.. Concentrations of PYY, GLP-1, ghrelin, and leptin were measured in 3 groups of young women: normal weight (n = 7), CT (n = 10), and AN (n = 12). Samples were collected every 4 h for 24 h.. PYY concentrations were significantly higher in CT subjects than in AN or control subjects. GLP-1 concentrations were significantly higher in AN than in CT subjects, whereas ghrelin was significantly higher in AN subjects than in control and CT subjects. CT subjects had the lowest ghrelin concentrations. Leptin concentrations were significantly lower in AN subjects. PYY and leptin circadian variations were not significantly different between CT and control subjects, whereas these profiles were blunted in AN subjects.. Orexigenic and anorexigenic hormones in CT contrast with an adaptative profile characterizing AN. The hormones appear to be valuable biomarkers for distinguishing these 2 categories of severely underweight subjects.

Topics: Absorptiometry, Photon; Adult; Analysis of Variance; Anorexia Nervosa; Appetite Regulation; Body Composition; Body Mass Index; Case-Control Studies; Circadian Rhythm; Energy Intake; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Peptide Hormones; Peptide YY; Thinness

Cholecystokinin (CCK), glucose dependent insulinotropic peptide (GIP), and glucagon-like peptide 1 (GLP-1) regulate satiety as enterogastrons and incretins. They also directly affect the satiety centers. Therefore, these peptides may participate in the pathogenesis of eating disorders. CCK, GIP, and GLP-1 secretion were studied in 13 adolescent girls suffering from simple obesity, 13 girls with anorexia nervosa, and 10 healthy girls. Each girl was subjected to an oral glucose tolerance test (OGTT) and standard meal test. Blood was collected before stimulation and at 15, 30, 60, and 120 min. The concentrations of all peptides were determined by RIA commercial kits. Fasting and postprandial levels of these peptides as well as integrated outputs were measured. High postprandial levels of CCK observed in the girls with anorexia may aggravate the course of this disease by intensifying nausea and vomiting. Low postprandial level of GLP-1 in girls with simple obesity may be responsible for excessive ingestion of food and weaker inhibition of gastric emptying, which also leads to obesity.

Topics: Adolescent; Anorexia Nervosa; Child; Cholecystokinin; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Male; Obesity; Peptide Fragments; Protein Precursors; Radioimmunoassay

GLP-1, with its insulinotropic properties and direct action on satiety center in the brain, may be the main hormone regulating the amount of ingested food. In this study, GLP-1 secretion was investigated in age-matched adolescent girls (14 +/- 2 years): 13 with anorexia nervosa (BMI 14.8 +/- 1.4 kg/m(2)), 13 with simple obesity (BMI 33.0 +/- 3.3 kg/m(2)) and 10 healthy girls as a control group (BMI 21.6 +/- 0.7 kg/m(2)). Each girl was subjected to OGTT and standard meal tests after a 12 h overnight fast. Blood samples were collected before and 15, 30, 60, and 120 min after the stimulation. The mean fasted GLP-1 levels in simple obesity group (1.6 +/- 0.3 pmol/l) and in anorexia nervosa group (1.7 +/- 0.3 pmol/l) were significantly lower than those in the control group (2.6 +/- 0.4 pmol/l) (p < 0.05 in both cases). The highest peak concentration of GLP-1 was observed in the control group after both stimuli. In each group, the mean integrated GLP-1 outputs were almost twice as high after OGTT than after the test meal (p < 0.001 in each case). In our opinion, low secretion of GLP-1 in girls with simple obesity may seriously and negatively influence the course of this disease. On the other hand, low GLP-1 levels in girls with anorexia nervosa are beneficial and promote appetite.

Topics: Adolescent; Anorexia Nervosa; Blood Glucose; Fasting; Feeding and Eating Disorders; Female; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Obesity; Peptide Fragments; Protein Precursors; Satiation