The conscious Göttingen minipig as a model for studying rapid pulsatile insulin secretion in vivo

Aims/hypothesis. Pulsatile secretionis important for insulin action and suitable animal models are important tools for examining the role of impaired pulsatile insulinsecretion as a possible link between beta-cell mass, function and morphology and insulin resistance. This study examines the vascular sampling site, insulin kinetics, pulsatility and the response to glucose pulse entrainment to evaluate the Gottingen minipigas a model for studying pulsatile insulinsecretion. Methods. Basal and glucose entrained insulin secretion was examined in normal minipigs and evaluated by autocorrelation, cross correlation and deconvolution. Results. Cross correlation showed a relation between oscillations in insulin concentrations in the portal and jugular veinin anaesthetised animals (p<0.001 in all animals), confirming the usefulness of jugular veinsampling for pulse detection. Jugular veinsampling in conscious animals showed obvious oscillations allowing estimates of burst shape and insulin kinetics. Glucose entrainment improved the pulsatile pattern (autocorrelation: 0.555±0.148 entrained vs 0.350±0.197 basal, p=0.054). Deconvolutionanalysis resolved almost all insulin release as secretory bursts (69±20 basal vs 99.5±1.2% entrained, p<0.01) with a pulse interval (min) of 6.6±2.2 (basal) and 9.4±1.5 (entrained) (p<0.05) and a pulse mass (pmol/l per pulse) which was higher after entrainment (228±117 vs 41.2±18.6 basal, p<0.001). Conclusion/interpretation. The ability to fit kinetic parameters directly by deconvolutionof peripheral endogenous insulin concentration time series in combination with the suitability of jugular veinsampling, rapid kinetics and entrainability makes the Gottingen minipigideal for mechanistic studies of insulin pulsatility and its effects on insulin action.