Assessment of the Role of Metabolic Determinants on the Relationship between Insulin Sensitivity and Secretion

PLoS One. 2016 Dec 21;11(12):e0168352. doi: 10.1371/journal.pone.0168352. eCollection 2016.

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.

Aim: 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.

Conclusion: 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.

MeSH terms

  • Adult
  • Animals
  • C-Peptide / blood
  • Chemokine CCL5 / blood
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Chemokines / blood
  • Exercise
  • Fatty Acids, Nonesterified / blood
  • Female
  • Glucose / metabolism
  • Glucose Tolerance Test
  • Healthy Volunteers
  • Humans
  • In Vitro Techniques
  • Insulin / metabolism*
  • Insulin Secretion
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Lactic Acid / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology

Substances

  • C-Peptide
  • Chemokine CCL5
  • Chemokines
  • Fatty Acids, Nonesterified
  • Insulin
  • Interleukin-6
  • Interleukin-8
  • Recombinant Proteins
  • Lactic Acid
  • Glucose

Grants and funding

The work was supported by the following: Fondo Nacional de Desarrollo Cientifico y Tecnologico 1130217, http://www.conicyt.cl/fondecyt/ (JEG); Vicerrectoria Academica - Pontificia Universidad de Chile, http://investigacion.uc.cl/ (JEG).