Abstract
Aims/hypothesis. Pulsatile secretion is important for insulin action and suitable animal models are important tools for examining the role
of impaired pulsatile insulin secretion 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 Göttingen minipig as a model for studying pulsatile insulin secretion.
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 vein in anaesthetised
animals (p<0.001 in all animals), confirming the usefulness of jugular vein sampling for pulse detection. Jugular vein sampling 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). Deconvolution analysis 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 deconvolution of peripheral endogenous insulin concentration time series
in combination with the suitability of jugular vein sampling, rapid kinetics and entrainability makes the Göttingen minipig
ideal for mechanistic studies of insulin pulsatility and its effects on insulin action.
Pulsatile insulin secretion insulin kinetics deconvolution in vivo model insulin action
Electronic Publication