title: Acute peripheral administration of synthetic human GLP-1 (7-36 amide) decreases circulating IL-6 in obese patients with type 2 diabetes mellitus: a potential role for GLP-1 in modulation of the diabetic pro-inflammatory state?
abstract: BACKGROUND
  To explore the effects of acute administration of GLP-1 and GIP on circulating levels of key adipocyte-derived hormones and gut-brain peptides with established roles in energy and appetite regulation, modulation of insulin sensitivity and inflammation.
  
  
  METHODS
  Six obese male patients with diet-treated type 2 diabetes (T2DM) and 6 healthy lean subjects were studied. The protocol included 4 experiments for each participant that were carried out in randomised order and comprised: GLP-1 infusion at a rate of 1 pmol/kg/min for 4h, GIP at a rate of 2 pmol/kg/min, GLP-1+GIP and placebo infusion. Plasma leptin, adiponectin, IL-6, insulin, ghrelin and obestatin were measured at baseline, 15, 60, 120, 180 and 240 min following the start of infusion.
  
  
  RESULTS
  Patients with T2DM had higher baseline IL-6 compared with healthy [day of placebo infusion: T2DM IL-6 mean (SEM) 1.3 (0.3) pg/ml vs 0.3 (0.1)pg/ml, p=0.003]. GLP-1 infusion in T2DM was associated with a significant reduction in circulating IL-6 [baseline IL-6 1.2 pg/ml vs IL-6=0.7 at 120 min, p=0.0001; vs IL-6=0.8 at 180 min, p=0.001]. There was no significant change in leptin, adiponectin, ghrelin or obestatin compared to baseline on all 4 experimental days in both groups.
  
  
  CONCLUSIONS
  Short-term infusion of supraphysiological concentrations of GLP-1 in T2DM results in suppression of IL-6, a key inflammatory mediator strongly linked to development of obesity and T2DM-related insulin resistance. It remains to be confirmed whether GLP-1-based diabetes therapies can impact favourably on cardiovascular outcomes.
authors.affiliation: Diabetes & Endocrinology Clinical Research Group, University Hospital Aintree, Clinical Sciences Centre, Lower Lane, Liverpool L9 7AL, United Kingdom. Electronic address: cdaousi@liverpool.ac.uk.
authors.forename: Christina
authors.initials: C
authors.lastname: Daousi
authors.affiliation: Department of Diabetes & Endocrinology, Derriford Hospital, Plymouth, Devon PL6 8DH, United Kingdom.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Pinkney
authors.affiliation: Diabetes & Endocrinology Clinical Research Group, University Hospital Aintree, Clinical Sciences Centre, Lower Lane, Liverpool L9 7AL, United Kingdom.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cleator
authors.affiliation: Diabetes & Endocrinology Clinical Research Group, University Hospital Aintree, Clinical Sciences Centre, Lower Lane, Liverpool L9 7AL, United Kingdom.
authors.forename: John P
authors.initials: JP
authors.lastname: Wilding
authors.affiliation: Department of Clinical Biochemistry & Metabolic Medicine, Royal Liverpool University Hospital, Prescot Street, Liverpool L69 8XP, United Kingdom.
authors.forename: L R
authors.initials: LR
authors.lastname: Ranganath
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications* / Q000188:drug therapy; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015850:Interleukin-6 / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000150:complications*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*
chemical_list: D015850:Interleukin-6; D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; D052216:Glucagon-Like Peptide 1