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

Abstract

BackgroundInsulin 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.AimTo evaluate the association between whole-body carbohydrate oxidation and circulating factors with insulin secretion to consecutive oral glucose loading in non-diabetic individuals.MethodsCarbohydrate 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.ResultsCarbohydrate 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.ConclusionWhole-body carbohydrate oxidation appears to have no influence on insulin secretion or putative circulating mediators. IL8 may be a potential factor influencing insulin secretion.

Pathophysiological role of metabolic flexibility on metabolic health

“…The second point, and likely more relevant, refers to the fact that insulin variance is just another way to describe hyperinsulinemia. From our studies, serum insulin variance calculated over 3 h (eight time points) after an OGTT was highly related with average insulinemia ( r = 0.84; p < 0.0001; n = 51; unpublished analysis from Galgani, Gomez et al 24 ). The concept elaborated in this review considers crucial the inclusion of fuel availability at tissue/cellular level to identify cellular/molecular determinants of MetF.…”

“…During fasting, endogenous fatty acid supply is abundant, 23 which increases its contribution to ATP production, thus progressively replacing the glucose supply. Upon ingestion of foods containing carbohydrates, glucose supply increases and thus boosts glucose oxidation as the main energy source 24 . This ability to alternate energy fuels depending on fuel availability (i.e., MetF) assures a constant and sufficient energy supply to organs and cells.…”

“…Upon ingestion of foods containing carbohydrates, glucose supply increases and thus boosts glucose oxidation as the main energy source. 24 This ability to alternate energy fuels depending on fuel availability (i.e., MetF) assures a constant and sufficient energy supply to organs and cells. At whole-body level, MetF also appears to influence energy intake and energy balance, [25][26][27] because impaired MetF associates with an increased risk of weight gain.…”

Influence of a Gas Exchange Correction Procedure on Resting Metabolic Rate and Respiratory Quotient in Humans

“…Gas exchange was measured over the last 20 minutes of each hour after each OGTT, which was followed by the indirect calorimetry correction procedure. Blood analysis as well as corrected metabolic rate and RQ were reported elsewhere .…”

Effect of Human Myotubes-Derived Media on Glucose-Stimulated Insulin Secretion

“…Some of them (IL6, fractalkine/CX3CL1, and RANTES/CCL5) have been also shown to influence in vitro insulin secretion [ 4 , 5 , 19 , 20 ]. In turn, we recently reported that circulating IL8/CXCL8 concentration directly associates with in vivo insulin secretion in humans [ 21 ].…”