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


CONCLUSIONS
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.
Larsen
M O
MO
Department of Pharmacological Research I, Pharmacology, Research & Development, Novo Nordisk A/S, Novo Allé 6A1.005, 2880 Bagsvaerd, Denmark. mmla@novonordisk.com
Elander
M
M
Sturis
J
J
Wilken
M
M
Carr
R D
RD
Rolin
B
B
Pørksen
N
N
D000768:Anesthesia, General; D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007601:Jugular Veins; D007700:Kinetics; D023421:Models, Animal; D011169:Portal Vein; D013552:Swine; D013556:Swine, Miniature
D007328:Insulin