title: Simultaneous GLP-1 and insulin administration acutely enhances their vasodilatory, antiinflammatory, and antioxidant action in type 2 diabetes.
abstract: OBJECTIVE
  To test the hypothesis that the simultaneous administration of GLP-1 and insulin may increase their vasodilatory, antiinflammatory, and antioxidant action in type 2 diabetes.
  
  
  METHODS
  In two groups of persons with type 2 diabetes, two sets of experiments were performed. The first group had two normoglycemic-normoinsulinemic clamps with or without GLP-1 and two normoglycemic-hyperinsulinemic clamps with or without GLP-1. The second group had two hyperglycemic-normoinsulinemic clamps and two hyperglycemic-hyperinsulinemic clamps with or without GLP-1.
  
  
  RESULTS
  During the normoglycemic-hyperinsulinemic clamp, flow-mediated dilatation (FMD) increased, while soluble intercellular adhesion molecule (sICAM-1), plasma 8-iso-prostaglandin F2α (8-iso-PGF2α), nitrotyrosine, and interleukin (IL)-6 decreased compared with normoglycemic-normoinsulinemic clamp. Similar results were obtained with the infusion of GLP-1 during the normoglycemic-normoinsulinemic clamp. The combination of hyperinsulinemia and GLP-1 in normoglycemia was accompanied by a further FMD increase and sICAM-1, 8-iso-PGF2α, nitrotyrosine, and IL-6 decrease. During the hyperglycemic-normoinsulinemic clamp, FMD significantly decreased, while sICAM-1, 8-iso-PGF2α, nitrotyrosine, and IL-6 significantly increased. When hyperglycemia was accompanied by hyperinsulinemia or by the simultaneous infusion of GLP-1, these phenomena were attenuated. The simultaneous presence of hyperinsulinemia and GLP-1 had an increased beneficial effect.
  
  
  CONCLUSIONS
  Our results show that the combination of insulin and GLP-1 is more effective than insulin or GLP-1 alone in improving endothelial dysfunction, inflammation, and oxidative stress in type 2 diabetes.
authors.affiliation: Insititut d'Investigacions Biomèdiques August Pi i Sunyer and CIBERDEM, Hospital Clínic Barcelona, Barcelona, Spain aceriell@clinic.ub.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ceriello
authors.affiliation: Insititut d'Investigacions Biomèdiques August Pi i Sunyer and CIBERDEM, Hospital Clínic Barcelona, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Novials
authors.affiliation: Insititut d'Investigacions Biomèdiques August Pi i Sunyer and CIBERDEM, Hospital Clínic Barcelona, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Canivell
authors.affiliation: Insititut d'Investigacions Biomèdiques August Pi i Sunyer and CIBERDEM, Hospital Clínic Barcelona, Barcelona, Spain.
authors.forename: Lucia
authors.initials: L
authors.lastname: La Sala
authors.affiliation: Insititut d'Investigacions Biomèdiques August Pi i Sunyer and CIBERDEM, Hospital Clínic Barcelona, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Pujadas
authors.affiliation: Division of Metabolic Diseases, Center of Excellence for Cardiovascular Diseases, 2nd University of Naples, Naples, Italy.
authors.forename: Katherine
authors.initials: K
authors.lastname: Esposito
authors.affiliation: Metabolic and Nutrition Research Center on Diabetes, Italian National Research Center on Aging, Istituto Nazionale Riposo e Cura Anziani-Istituto di Ricovero e Cura a Carattere Scientifico, Ancona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Testa
authors.affiliation: Department of Cardiovascular and Metabolic Diseases, Istituto di Ricovero e Cura a Carattere Scientifico Gruppo Multimedica, Sesto San Giovanni, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Bucciarelli
authors.affiliation: Department of Cardiovascular and Metabolic Diseases, Istituto di Ricovero e Cura a Carattere Scientifico Gruppo Multimedica, Sesto San Giovanni, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rondinelli
authors.affiliation: Department of Cardiovascular and Metabolic Diseases, Istituto di Ricovero e Cura a Carattere Scientifico Gruppo Multimedica, Sesto San Giovanni, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Genovese
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D006946:Hyperinsulinism / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D007004:Hypoglycemic Agents; D007328:Insulin; D015850:Interleukin-6; D014665:Vasodilator Agents; C075750:8-epi-prostaglandin F2alpha; D052216:Glucagon-Like Peptide 1; D015237:Dinoprost