title: Effects of chronic slow release-lanreotide treatment on insulin-like growth factor system and metabolic parameters in acromegalic patients.
abstract: Insulin and IGF binding protein (IGFBP)-1 are linked by negative association. Somatostatin (SS) reduces insulin secretion by acting on pancreatic β-cell and also by decreasing GH secretion. SS analogues in acromegaly reduce total IGF-I levels inhibiting GH hypersecretion, but they also reduce free IGF-I bioactivity increasing IGFBP-1 levels by inducing insulin decrease. In 13 acromegalic patients we studied GH, IGF system, insulin, and glucagon levels at baseline and at 7 days, 1 and 6 months under treatment with slow release (SR)-lanreotide (LAN) (60 mg im monthly). The hormonal and metabolic response to arginine (ARG) (0.5 g/kg iv in 30 min) was also studied at each time point. LAN decreased GH, total IGF-I, and IGFBP-3 levels at each time point. Insulin and glucagon levels were reduced, while IGFBP-1 and free IGF-I levels were increased by LAN at day 7 and after 1 month only. LAN did not modify the GH, insulin, glucagon, glucose, and IGFBP-1 responses to ARG. At each time point ARG-induced insulin increase was coupled to increase in glucagon and IGFBP-1 levels. This study shows that acromegalic patients under chronic treatment with LAN display: a) inhibition of GH and total IGF-I levels, not coupled to persistent decrease in free IGF-I levels; b) persistent decrease in IGFBP- 3 but transient decrease and increase in insulin and IGFBP- 1, respectively; c) unchanged hormonal and metabolic response to ARG. Our findings also show that ARG stimulates IGFBP-1 despite marked increase in insulin secretion; this escape from the negative relationship linking insulin and IGFBP- 1 would likely reflect the ARG-induced glucagon increase.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Gasco
authors.forename: G
authors.initials: G
authors.lastname: Beccuti
authors.forename: F
authors.initials: F
authors.lastname: Marotta
authors.forename: N
authors.initials: N
authors.lastname: Prencipe
authors.forename: M
authors.initials: M
authors.lastname: Maccario
authors.forename: J
authors.initials: J
authors.lastname: Janssen
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Lely
authors.forename: E
authors.initials: E
authors.lastname: Ghigo
authors.forename: S
authors.initials: S
authors.lastname: Grottoli
mesh_terms: D000172:Acromegaly / Q000097:blood* / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D005260:Female; D005934:Glucagon / Q000097:blood; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D003692:Delayed-Action Preparations; C032231:IGFBP1 protein, human; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005934:Glucagon