title: GIP does not potentiate the antidiabetic effects of GLP-1 in hyperglycemic patients with type 2 diabetes.
abstract: OBJECTIVE
  The incretin glucagon-like peptide 1 (GLP-1) exerts insulinotropic activity in type 2 diabetic patients, whereas glucose-dependent insulinotropic polypeptide (GIP) no longer does. We studied whether GIP can alter the insulinotropic or glucagonostatic activity of GLP-1 in type 2 diabetic patients.
  
  
  METHODS
  Twelve patients with type 2 diabetes (nine men and three women; 61 ± 10 years; BMI 30.0 ± 3.7 kg/m²; HbA(1c) 7.3 ± 1.5%) were studied. In randomized order, intravenous infusions of GLP-1(7-36)-amide (1.2 pmol · kg⁻¹ · min⁻¹), GIP (4 pmol · kg⁻¹ · min⁻¹), GLP-1 plus GIP, and placebo were administered over 360 min after an overnight fast (≥ 1 day wash-out period between experiments). Capillary blood glucose, plasma insulin, C-peptide, glucagon, GIP, GLP-1, and free fatty acids (FFA) were determined.
  
  
  RESULTS
  Exogenous GLP-1 alone reduced glycemia from 10.3 to 5.1 ± 0.2 mmol/L. Insulin secretion was stimulated (insulin, C-peptide, P < 0.0001), and glucagon was suppressed (P = 0.009). With GIP alone, glucose was lowered slightly (P = 0.0021); insulin and C-peptide were stimulated to a lesser degree than with GLP-1 (P < 0.001). Adding GIP to GLP-1 did not further enhance the insulinotropic activity of GLP-1 (insulin, P = 0.90; C-peptide, P = 0.85). Rather, the suppression of glucagon elicited by GLP-1 was antagonized by the addition of GIP (P = 0.008). FFA were suppressed by GLP-1 (P < 0.0001) and hardly affected by GIP (P = 0.07).
  
  
  CONCLUSIONS
  GIP is unable to further amplify the insulinotropic and glucose-lowering effects of GLP-1 in type 2 diabetes. Rather, the suppression of glucagon by GLP-1 is antagonized by GIP.
authors.affiliation: Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Mentis
authors.forename: Irfan
authors.initials: I
authors.lastname: Vardarli
authors.forename: Lars D
authors.initials: LD
authors.lastname: Köthe
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Deacon
authors.forename: Michael
authors.initials: M
authors.lastname: Theodorakis
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nauck
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004347:Drug Interactions; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D007004:Hypoglycemic Agents; D054795:Incretins; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1