glucagon-like-peptide-2 and glucagon-like-peptide-1-(7-36)amide

To identify possible abnormalities specific for obesity in hypopituitary patients.. Cross-sectional case-control study. MEASUREMENTS AND STUDY SUBJECTS: Body composition (DEXA) and measurements of fasting plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptides (GLPs), insulin, C-peptide, glucose, leptin and lipids were performed in 25 hypopituitary patients (15 obese, 10 normal weight) and 26 BMI and age-matched healthy controls (16 obese, 10 normal weight). All hypopituitary patients had GH deficiency and received adequate substitution therapy on this and other deficient axes (3 +/- 1).. Fasting GIP-levels were significantly higher in obese hypopituitary patients compared to lean hypopituitary patients (P < 0.01), while the fasting concentrations of GLP-1 and GLP-2 were comparable between obese and lean hypopituitary patients. The same trend was seen in obese healthy controls vs. lean controls. No differences were observed in glucose, insulin or C-peptide between the hypopituitary patients and the controls. Leptin levels were increased in obese hypopituitary patients compared to lean hypopituitary patients when adjusted for gender. At least a 2-fold higher level of leptin was observed in women compared to men in both patient groups and healthy controls. Lean female hypopituitary patients had higher leptin levels than matched controls.. Fasting levels of GIP were elevated in obese substituted hypopituitary patients, while fasting concentrations of GLPs were similar. Obese hypopituitary patients had the same degree of hyperinsulinaemia, affected glucose tolerance, dyslipoproteinaemia and central obesity as obese healthy controls. Further studies are required to identify the possible biochemical reasons for obesity in patients with apparently well-substituted hypopituitarism.

Topics: Adult; Anthropometry; Body Composition; Case-Control Studies; Cross-Sectional Studies; Fasting; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Human Growth Hormone; Humans; Hypopituitarism; Leptin; Lipids; Male; Middle Aged; Obesity; Peptide Fragments; Peptides; Thinness

We investigated the effect of GLPs on glucose uptake in isolated rat adipocytes. GLP-1(7-36)amide significantly enhanced glucose uptake in the presence of 1 nM insulin. GLP-1(7-36)amide at 15 nM increased glucose uptake maximally by 56.4% as compared with 1 nM insulin alone (P < 0.01). In contrast, with less than 1 nM insulin or without insulin GLP-1(7-36)amide showed no effect on glucose uptake. Full-sequence GLP-1(1-37) at 15 nM in the presence of 1 nM insulin increased glucose uptake by 24.6% as compared with 1 nM insulin alone (P < 0.05). GLP-2 showed no effect on glucose uptake. Further, we examined the effect of GLP-1(7-36)amide on cAMP content in isolated rat adipocytes. Insulin at 1 nM caused a significant decrease of cAMP content. The combination of 15 nM GLP-1(7-36)amide and 1 nM insulin caused a further reduction of cAMP content. These data indicate that GLP-1(7-36)amide possesses augmentative effects on insulin action in isolated rat adipocytes. Furthermore, it is suggested that the stimulatory effect of GLP-1(7-36)amide occurs through the reduction of intracellular cAMP content.

Topics: 1-Methyl-3-isobutylxanthine; Adipocytes; Animals; Colforsin; Cyclic AMP; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Glucose; Insulin; Male; Peptide Fragments; Peptides; Phosphodiesterase Inhibitors; Rats

Injury, inflammation, or resection of the small intestine results in severe compromise of intestinal function. Nevertheless, therapeutic strategies for enhancing growth and repair of the intestinal mucosal epithelium are currently not available. We demonstrate that nude mice bearing subcutaneous proglucagon-producing tumors exhibit marked proliferation of the small intestinal epithelium. The factor responsible for inducing intestinal proliferation was identified as glucagon-like peptide 2 (GLP-2), a 33-aa peptide with no previously ascribed biological function. GLP-2 stimulated crypt cell proliferation and consistently induced a marked increase in bowel weight and villus growth of the jejunum and ileum that was evident within 4 days after initiation of GLP-2 administration. These observations define a novel biological role for GLP-2 as an intestinal-derived peptide stimulator of small bowel epithelial proliferation.

Topics: Animals; Cell Division; Glicentin; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Glucagonoma; Ileum; Immunohistochemistry; Intestinal Mucosa; Jejunum; Kinetics; Mice; Mice, Nude; Organ Size; Pancreatic Hormones; Pancreatic Neoplasms; Peptide Fragments; Peptides; Proglucagon; Proliferating Cell Nuclear Antigen; Protein Precursors; Rats; Transplantation, Heterologous

This study was designed to determine the effects of glucagon-like peptides (GLP) on arterial blood pressure and heart rate. Although glucagon caused a minimal effect and GLP-1-(1-37) produced a moderate increase of both systolic and diastolic blood pressure, GLP-1-(7-36) amide induced the greatest increases in both parameters. Systolic and diastolic blood pressure and heart rate values increased when doses of the peptides were increased. By contrast, GLP-2 did not modify either arterial blood pressure or heart rate values. To determine whether the effects of GLP-1-(7-36) amide were mediated through catecholamines, the rats were pretreated with reserpine, propranolol, or phentolamine before administration of the peptide. In these three experimental groups, GLP-1-(7-36) amide increases mean arterial blood pressure and heart rate to the same level or even greater than that observed in nonpretreated rats. These findings indicate that GLP-1-(7-36) amide significantly increases arterial blood pressure and heart rate and that these effects are not mediated through catecholamines.

Topics: Animals; Blood Pressure; Catecholamines; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Heart Rate; Male; Peptide Fragments; Peptides; Rats; Rats, Sprague-Dawley; Reserpine