oxyntomodulin and Adenoma

Topics: Adenoma; Adrenocorticotropic Hormone; Erythropoietin; Female; Glucagon-Like Peptides; Gonadotropins; Hormones, Ectopic; Humans; Hypercalcemia; Infant; Insulin; Insulin Secretion; Kidney Neoplasms; Male; Middle Aged; Parathyroid Hormone; Parathyroid Neoplasms; Placental Lactogen; Prolactin; Prostaglandins A; Renin

To study the effect of octreotide on glucagon-like peptide (7-36) amide (GLP-1) and insulin secretion in patients with pituitary tumors during preoperative treatment and in healthy subjects.. Open design prospective clinical study.. Eighteen patients with pituitary macroadenomas (13 clinically nonfunctioning (NFA; 11/13 had GH insufficiency), 5 GH secreting (GHA)) received preoperative octreotide treatment: 3x100 microg/day s. c. for 3 months, and 3x500 microg/day s.c. for an additional 3 months. Seven healthy subjects received (for ethical reasons) only 3x100 microg/day for 10 days. A standardized meal (St-M) test, oral glucose test (oGTT) and i.v. glucose test (ivGTT) were done before octreotide therapy, on days 1, 2 and 3 (D1,2,3), after 3 months (M3) and 6 months (M6) of octreotide treatment in the patients, and before treatment, on D1,2,3 and on D8,9,10 of octreotide treatment in the healthy subjects. Serum GLP-1, insulin and GH as well as plasma glucose were determined for 180 min (oGTT, St-M) or 120 min (ivGTT).. Pretreatment fasting GLP-1 concentrations as well as integrated responses (area under the curve 0-180 min) to oGTT and St-M were not significantly different between NFA, GHA and healthy subjects. During the oGTT, octreotide initially almost abolished the early (0-60 min) and diminished the late (60-180 min) GLP-1 and insulin responses in patients and healthy subjects. At M6 integrated insulin responses had significantly recovered, while the increase in GLP-1 response failed to reach significance (GLP-1: 56.5% of pretreatment at D2 versus 93.5% at M6 and 41.2 versus 63.1% in NFA and GHA respectively; insulin: 50.2 versus 71.2% and 35.5 versus 70. 4%). An escape of GLP-1 and insulin in healthy subjects (D2 versus D9) was not significant. Intestinal glucose absorption was apparently not reduced, since the early glucose rise was similar before and during octreotide treatment. During the St-M the GLP-1 and insulin responses were similarly suppressed by octreotide and recovered during ongoing treatment (GLP-1: 49.6% of pretreatment at D1 versus 79.0% at M6 in NFA and 46.9 versus 52.9% in GHA. Insulin: 27.6 versus 83.9% and 23.5 versus 54.4%). The escape was significant in NFA but not in GHA. In the healthy subjects the escape was already significant on D8 (GLP-1: 39.5% of pretreatment at D1 versus 68.3% at D8; insulin: 36.6 versus 53.8%). During the ivGTT GLP-1 did not increase. The early insulin response (0-30 min) was abolished by octreotide, followed by a reduced peak at 60 min. The reduction of the integrated insulin response during ivGTT was similar to that during oGTT. An insulin escape reached significance only for NFA (52. 6% of pretreatment at D3 versus 66.7% at M6). Glucose tolerance (KG value) deteriorated and did not improve during ongoing treatment. Octreotide suppressed the median GH concentration (8h profile) of the GHA patients from 10.3 microg/l (pretreatment) to 5.8, 6.3 and 3. 7 microg/l at D4, M3 and M6 with no escape. GH was 1.5 microg/l postoperatively.. Octreotide abolishes the early and diminishes the late GLP-1 and insulin responses to oGTT and St-M in NFA and GHA patients and in healthy subjects. In contrast to GH, both hormones partially escape from suppression during ongoing therapy. During treatment with our conventional octreotide doses suppression of insulin secretion is maximal. Under these conditions an effect of the additional loss of GLP-1 is not apparent. Basal GLP-1 concentrations and integrated responses to oGTT and St-M were similar in healthy subjects and in patients with GH excess or GH insufficiency.

Topics: Acromegaly; Adenoma; Adult; Antineoplastic Agents, Hormonal; Blood Glucose; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose Tolerance Test; Hormones; Human Growth Hormone; Humans; Insulin; Male; Middle Aged; Octreotide; Peptide Fragments; Pituitary Neoplasms; Prospective Studies; Protein Precursors

Glucagon-like peptide 2 (GLP-2) is an intestinotrophic mediator with therapeutic potential in conditions with compromised intestinal capacity. However, growth stimulation of the intestinal system may accelerate the growth of existing neoplasms in the intestine.. In the present study, the effects of GLP-2 treatment on the growth of chemically induced colonic neoplasms were investigated.. In 210 female C57bl mice, colonic tumours were initially induced with the methylating carcinogen 1,2-dimethylhydrazine (DMH) and mice were then treated with GLP-2. Two months after discontinuation of the carcinogen treatment, 135 of the mice were allocated to one of six groups which were treated twice daily with 25 microg GLP-2, 25 microg Gly2-GLP-2 (stable analogue), or phosphate buffered saline for a short (10 days) or long (one month) period. The remaining 75 mice had a treatment free period of three months and were then allocated to groups subjected to long term treatment, as above.. Colonic polyps developed in 100% of the mice, regardless of treatment. Survival data revealed no statistical significant differences among the different groups but histopathological analysis demonstrated a clear and significant increase in tumour load of mice treated with Gly2-GLP-2. The tumour promoting effect of native GLP-2 was less pronounced but the number of small sized polyps increased following long term treatment.. The present results clearly indicate that GLP-2 promotes the growth of mucosal neoplasms. Our findings highlight the need for future investigations on the effects of GLP-2 in conditions needing long time treatment or with increased gastrointestinal cancer susceptibility.

Topics: Adenoma; Animals; Body Weight; Colonic Neoplasms; Colonic Polyps; Female; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Intestinal Mucosa; Intestine, Small; Mice; Mice, Inbred C57BL; Organ Size; Peptides

We examined 12 depressed tubular adenomas of the stomach pathologically and immunohistochemically in order to clarify the difference between the depressed type and the elevated type. Depressed tubular adenomas showed shallow mucosal depression and, of the 12, nine were endoscopically diagnosed as early gastric cancer. Histologically, the adenoma cells showed dysplasia in varying degree and focal adenocarcinoma occurred in two adenomas measuring over 2 cm. The mean height of the adenoma glands was 0.63 +/- 0.31 mm in the 12 depressed adenomas and 1.32 +/- 0.43 mm in 44 elevated adenomas, while the mean heights of the subjacent mucosa were 0.18 +/- 0.19 mm and 1.07 +/- 0.71 mm, respectively. Thus, depressed adenomas resulted from paucity of the mucosa subjacent to the adenoma glands and the height of the adenomatous glands was half that found in the elevated type. Goblet cells, a variety of endocrine cells and lysozyme-containing cells were found in nine, nine and eight depressed adenomas, respectively, in variable numbers. Hyperplasia of these cells was also detected in depressed adenomas showing mild or moderate dysplasia. Immunohistochemical examination revealed no difference in the phenotypic expression of adenoma cells as between the depressed and the elevated type.

Topics: Adenoma; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Glicentin; Glucagon; Glucagon-Like Peptides; Humans; Immunohistochemistry; Muramidase; Peptide Fragments; Protein Precursors; Serotonin; Somatostatin; Stomach Neoplasms

Topics: Adenoma; Adenoma, Islet Cell; Adrenal Cortex; Female; Gastrins; Glucagon-Like Peptides; Humans; Hydrocortisone; Hyperplasia; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Parathyroid Neoplasms; Peptides; Thyroid Gland; Thyroid Hormones