title: Assessment of the Role of Metabolic Determinants on the Relationship between Insulin Sensitivity and Secretion.
abstract: BACKGROUND
  Insulin secretion correlates inversely with insulin sensitivity, which may suggest the existence of a crosstalk between peripheral organs and pancreas. Such interaction might be mediated through glucose oxidation that may drive the release of circulating factors with action on insulin secretion.
  
  
  OBJECTIVE
  To evaluate the association between whole-body carbohydrate oxidation and circulating factors with insulin secretion to consecutive oral glucose loading in non-diabetic individuals.
  
  
  METHODS
  Carbohydrate oxidation was measured after an overnight fast and for 6 hours after two 3-h apart 75-g oral glucose tolerance tests (OGTT) in 53 participants (24/29 males/females; 34±9 y; 27±4 kg/m2). Insulin secretion was estimated by deconvolution of serum C-peptide concentration, β cell function by mathematical modelling and insulin sensitivity from an OGTT. Circulating lactate, free-fatty acids (FFA) and candidate chemokines were assessed before and after OGTT. The effect of recombinant RANTES (regulated on activation, normal T cell expressed and secreted) and IL8 (interleukin 8) on insulin secretion from isolated mice islets was also measured.
  
  
  RESULTS
  Carbohydrate oxidation assessed over the 6-h period did not relate with insulin secretion (r = -0.11; p = 0.45) or β cell function indexes. Circulating lactate and FFA showed no association with 6-h insulin secretion. Circulating chemokines concentration increased upon oral glucose stimulation. Insulin secretion associated with plasma IL6 (r = 0.35; p<0.05), RANTES (r = 0.30; p<0.05) and IL8 (r = 0.41; p<0.05) determined at 60 min OGTT. IL8 was independently associated with in vivo insulin secretion; however, it did not affect in vitro insulin secretion.
  
  
  CONCLUSIONS
  Whole-body carbohydrate oxidation appears to have no influence on insulin secretion or putative circulating mediators. IL8 may be a potential factor influencing insulin secretion.
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.|UDA-Ciencias de la Salud, Carrera de Nutrición y Dietética, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Galgani
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gómez
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Mizgier
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Juan
authors.initials: J
authors.lastname: Gutierrez
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Santos
authors.affiliation: Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Olmos
authors.affiliation: Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
mesh_terms: D000328:Adult; D000818:Animals; D002096:C-Peptide / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000097:blood; D015444:Exercise; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D064368:Healthy Volunteers; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D002096:C-Peptide; D018946:Chemokine CCL5; D018925:Chemokines; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D015850:Interleukin-6; D016209:Interleukin-8; D011994:Recombinant Proteins; D019344:Lactic Acid; D005947:Glucose