Relationship between whole-body macronutrient oxidative partitioning and pancreatic insulin secretion/beta-cell function in non-diabetic humans

BACKGROUND: Glucose-stimulated insulin secretion correlates inversely with the degree of whole-body insulin sensitivity suggesting a crosstalk between peripheral organs and pancreas. Such sensing mechanism could be mediated by changes in glucose flux (uptake, oxidation or storage) in peripheral tissues that may drive insulin secretion. AIM: To relate whole-body non-protein respiratory quotient (npRQ), an index of macronutrient oxidative partitioning, with insulin secretion and beta-cell function in non-diabetic individuals. METHODS: Macronutrient oxidation was measured after an overnight fast and for 4h after a 75-g oral glucose tolerance test (OGTT) in 30 participants (15/15 males/females; 35+/-12y; 27+/-4kg/m2). Furthermore, npRQ was assessed for 24h in a metabolic chamber. Insulin secretion was estimated by deconvolution of serum C-peptide concentration (fasting and 4-h OGTT) and from 24-h urinary C-peptide excretion corrected for energy intake (metabolic chamber). beta-Cell function parameters were obtained by mathematical modeling, while insulin sensitivity was determined by a euglycemic-hyperinsulinemic clamp (120mU.m-2.min-1). RESULTS: Insulin secretion (from 24-h urinary C-peptide) correlated inversely with 24-h npRQ (r=-0.61; p=0.001), even after controlling for insulin sensitivity, energy balance, age and body mass index (r=-0.52; p=0.01). In turn, insulin secretion (from serum C-peptide) was not associated with fasting or OGTT npRQ. However, fasting npRQ was positively correlated with rate sensitivity (r=0.40; p<0.05) and marginally with glucose sensitivity (r=0.34; p=0.08). CONCLUSION: Macronutrient oxidative partitioning, specifically glucose oxidation, might play a role on the regulation of insulin secretion. Further studies should aim at identifying the signals linking these processes.