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

Jose E Galgani,Carmen Gómez,Jose L Santos,Pablo Olmos,Maria L Mizgier,Andrea Mari,Juan Gutierrez,Neil M Johannsen

doi:10.1371/journal.pone.0168352

Jose E Galgani, Carmen Gómez + Show 6 more

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https://doi.org/10.1371/journal.pone.0168352

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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.

Highlights

Glucose homeostasis requires of a complex interplay in which pancreatic β cells sense glucose concentration in order to release an appropriate amount of insulin
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
Insulin secretion associated with plasma interleukin 6 (IL6) (r = 0.35; p

Summary

Introduction

Glucose homeostasis requires of a complex interplay in which pancreatic β cells sense glucose concentration in order to release an appropriate amount of insulin. Considering that insulin sensitivity is mostly determined by peripheral tissues, one can hypothesize that an inter-organ humoral communication between these tissues and pancreas takes place. Some of them may be sensitive to changes in skeletal muscle insulin sensitivity or glucose metabolism [5]. One or a combination of these circulating factors might influence insulin secretion. Support for this hypothesis came from two skeletal muscle-specific genetic mice models, which are characterized by altered skeletal muscle glucose metabolism and abnormal in vivo insulin secretion [8,9]. Insulin secretion appears to be determined at central (β cells) and possibly peripheral (skeletal muscle, liver and adipose tissue) level.

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