title: Octreotide suppresses the incretin glucagon-like peptide (7-36) amide in patients with acromegaly or clinically nonfunctioning pituitary tumors and in healthy subjects.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Open design prospective clinical study.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepatology and Gastroenterology, Division of Neuroendocrinology and Metabolism, Charité, Campus Virchow-Klinikum, Humboldt Universität, Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Plöckinger
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: D
authors.initials: D
authors.lastname: Messerschmidt
authors.forename: W
authors.initials: W
authors.lastname: Hopfenmüller
authors.forename: H J
authors.initials: HJ
authors.lastname: Quabbe
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000188:drug therapy*; D000236:Adenoma / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001786:Blood Glucose; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D005951:Glucose Tolerance Test; D006728:Hormones / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000097:blood*; D010911:Pituitary Neoplasms / Q000097:blood / Q000188:drug therapy*; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood
chemical_list: D018931:Antineoplastic Agents, Hormonal; D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; C055453:glucagon-like peptide 1 (7-36)amide; D019382:Human Growth Hormone; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D015282:Octreotide