Relationship between whole-body macronutrient oxidative partitioning and pancreatic insulin secretion/β-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 ?-cell function in nondiabetic individuals.

Methods. Macronutrient oxidation wasmeasured after an overnight fast and for 4 h after a 75-g oral glucose tolerance test (OGTT) in 30 participants (15/15 males/females; 35 ± 12 y; 27 ± 4 kg/m2). Furthermore, npRQ was assessed for 24 h in a metabolic chamber. Insulin secretion was estimated by deconvolution of serumC-peptide concentration (fasting and 4-h OGTT) and from24-h urinary C-peptide excretion corrected for energy intake (metabolic chamber). β-Cell function parameters were obtained by mathematical modeling, while insulin sensitivity was determined by a euglycemichyperinsulinemic clamp (120 mU m2 min1).

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.