The reason why a sustained high concentration of insulin induces laminitis in horses remains unclear.
Cell proliferation occurs in the lamellae during insulin-induced laminitis and in other species high concentrations
of insulin can activate receptors for the powerful cell mitogen, insulin-like growth factor
(IGF)-1. The first aim of this study was to determine if IGF-1 receptors (IGF-1R) are activated in the hoof
during insulin-induced laminitis. Gene expression for IGF-1R and the insulin receptor (InsR) was measured
using qRT-PCR, in lamellar tissue from control horses and from horses undergoing a prolonged
euglycaemic, hyperinsulinaemic clamp (p-EHC), during the mid-developmental (24 h) and acute (46 h)
phases of insulin-induced laminitis. Gene expression for both receptors was decreased 13–32-fold
(P < 0.05) at both time-points in the insulin-treated horses.
A second aim was to determine if the down-regulation of the receptor genes could be accounted for by
an increase in circulating IGF-1. Serum IGF-1 was measured at 0, 10, 25 and 46 h post-treatment in horses
given a p-EHC for approximately 46 h, and in matched controls administered a balanced, electrolyte solution.
There was no increase in serum IGF-1 concentrations during the p-EHC, consistent with down-regulation
of both receptors by insulin. Stimulation of the IGF-1R by insulin may lead to inappropriate
lamellar epidermal cell proliferation and lamellar weakening, a potential mechanism for hyperinsulinaemic
laminitis. Targeting this receptor may provide insights into the pathogenesis or identify a novel therapy
for hyperinsulinaemic laminitis.
The reason why a sustained high concentration of insulin induces laminitis in horses remains unclear.Cell proliferation occurs in the lamellae during insulin-induced laminitis and in other species high concentrationsof insulin can activate receptors for the powerful cell mitogen, insulin-like growth factor(IGF)-1. The first aim of this study was to determine if IGF-1 receptors (IGF-1R) are activated in the hoofduring insulin-induced laminitis. Gene expression for IGF-1R and the insulin receptor (InsR) was measuredusing qRT-PCR, in lamellar tissue from control horses and from horses undergoing a prolongedeuglycaemic, hyperinsulinaemic clamp (p-EHC), during the mid-developmental (24 h) and acute (46 h)phases of insulin-induced laminitis. Gene expression for both receptors was decreased 13–32-fold(P < 0.05) at both time-points in the insulin-treated horses.A second aim was to determine if the down-regulation of the receptor genes could be accounted for byan increase in circulating IGF-1. Serum IGF-1 was measured at 0, 10, 25 and 46 h post-treatment in horsesgiven a p-EHC for approximately 46 h, and in matched controls administered a balanced, electrolyte solution.There was no increase in serum IGF-1 concentrations during the p-EHC, consistent with down-regulationof both receptors by insulin. Stimulation of the IGF-1R by insulin may lead to inappropriatelamellar epidermal cell proliferation and lamellar weakening, a potential mechanism for hyperinsulinaemiclaminitis. Targeting this receptor may provide insights into the pathogenesis or identify a novel therapyfor hyperinsulinaemic laminitis.
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