A potential role for lamellar insulin-like growth factor-1 receptor in the pathogenesis of hyperinsulinaemic laminitis

de Laat, Melody A., Pollitt, Christopher C., Kyaw-Tanner, Myat T., McGowan, Catherine M. and Sillence, Martin N. (2013) A potential role for lamellar insulin-like growth factor-1 receptor in the pathogenesis of hyperinsulinaemic laminitis. Veterinary Journal, 197 2: 302-306. doi:10.1016/j.tvjl.2012.12.026


Author de Laat, Melody A.
Pollitt, Christopher C.
Kyaw-Tanner, Myat T.
McGowan, Catherine M.
Sillence, Martin N.
Title A potential role for lamellar insulin-like growth factor-1 receptor in the pathogenesis of hyperinsulinaemic laminitis
Journal name Veterinary Journal   Check publisher's open access policy
ISSN 1090-0233
1532-2971
Publication date 2013-08-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.tvjl.2012.12.026
Open Access Status Not Open Access
Volume 197
Issue 2
Start page 302
End page 306
Total pages 5
Place of publication London, United Kingdom
Publisher Elsevier
Language eng
Formatted abstract
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.
Keyword Equine
Laminitis
Insulin
Insulin-like growth factor-1 receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Veterinary Science Publications
 
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