Diet-induced obesity in young mice interferes with the pancreatic intrinsic nervous system maturation and alters its control of insulin secretion

Pancreatic Intrinsic Nervous System (PINS) maturation goes on postnatally and is involved in the control of pulsatility and amplitude of insulin secretion (IS), both altered in obese and diabetic patients. The aim of our study was to determine the impact of obesity in infancy on PINS maturation and control of IS.C57BL/6J mice aged 4 weeks received a normal (ND) or a western diet (WD) for 12 weeks. 4 weeks old mice were used as initial controls (T0). After sacrifice, pancreases were placed in organ incubators for 1 h. The impact of PINS upon IS was studied by adding to the culture the nicotinic receptors agonist DMPP in presence or absence of L-NAME (inhibitor of NOS) or SNP (NO donor). Insulin was assayed in culture supernatants. PINS density and phenotype were determined by IHC.PINS density was less in ND compared to T0 mice, whereas there was no difference between WD and T0 mice. Cholinergic innervation significantly increased with age in both WD and ND mice whereas nitrergic innervation increased in ND mice and decreased in WD.PINS stimulation by DMPP induced a time-dependent increase in IS, significantly larger in ND compared to WD mice. IS profile was identical in WD and T0 mice. Addition of L-Name inhibited DMPP-induced IS in ND mice while SNP tended to reduce it. Neither L-Name nor SNP altered IS in WD mice.Our study suggests that WD induces neuroplastic changes in the PINS that could be involved in pancreatic dysfunctions observed during obesity