title: Glucose-dependent insulinotropic polypeptide (GIP) induces calcitonin gene-related peptide (CGRP)-I and procalcitonin (Pro-CT) production in human adipocytes.
abstract: BACKGROUND
  Increased plasma levels of glucose-dependent insulinotropic polypeptide (GIP), calcitonin CT gene-related peptide (CGRP)-I, and procalcitonin (Pro-CT) are associated with obesity. Adipocytes express functional GIP receptors and the CT peptides Pro-CT and CGRP-I. However, a link between GIP and CT peptides has not been studied yet.
  
  
  OBJECTIVE
  The objective of the study was the assessment of the GIP effect on the expression and secretion of CGRP-I and Pro-CT in human adipocytes, CGRP-I and CT gene expression in adipose tissue (AT) from obese vs. lean subjects, and plasma levels of CGRP-I and Pro-CT after a high-fat meal in obese patients.
  
  
  METHODS
  Human preadipocyte-derived adipocytes, differentiated in vitro, were treated with GIP. mRNA expression and protein secretion of CGRP-I and Pro-CT were measured. Human CGRP-I and CT mRNA expression in AT and CGRP-I and Pro-CT plasma concentrations were assessed.
  
  
  RESULTS
  Treatment with 1 nm GIP induced CGRP-I mRNA expression 6.9 ± 1.0-fold (P < 0.001 vs. control) after 2 h and CT gene expression 14.0 ± 1.7-fold (P < 0.001 vs. control) after 6 h. GIP stimulated CGRP-I secretion 1.7 ± 0.2-fold (P < 0.05 vs. control) after 1 h. In AT samples of obese subjects, CGRP-I mRNA expression was higher in sc AT (P < 0.05 vs. lean subjects), whereas CT expression was higher in visceral AT (P < 0.05 vs. lean subjects). CGRP-I plasma levels increased after a high-fat meal in obese patients.
  
  
  CONCLUSIONS
  GIP induces CGRP-I and CT expression in human adipocytes. Therefore, elevated Pro-CT and CGRP-I levels in obesity might result from GIP-induced Pro-CT and CGRP-I release in AT and might be triggered by a high-fat diet. How these findings relate to the metabolic complications of obesity warrants further investigations.
authors.affiliation: University Hospital Basel, Department of Biomedicine, Metabolism Group, Hebelstrasse 20, CH-4031 Basel, Switzerland. katharina.timper@yahoo.de
authors.forename: Katharina
authors.initials: K
authors.lastname: Timper
authors.forename: Jean
authors.initials: J
authors.lastname: Grisouard
authors.forename: Tanja
authors.initials: T
authors.lastname: Radimerski
authors.forename: Kaethi
authors.initials: K
authors.lastname: Dembinski
authors.forename: Ralph
authors.initials: R
authors.lastname: Peterli
authors.forename: Andreas
authors.initials: A
authors.lastname: Häring
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Frey
authors.forename: Henryk
authors.initials: H
authors.lastname: Zulewski
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D002116:Calcitonin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D009767:Obesity, Morbid / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: C000606589:CALCA protein, human; D004041:Dietary Fats; D011498:Protein Precursors; D012333:RNA, Messenger; D005749:Gastric Inhibitory Polypeptide; D002116:Calcitonin; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide