Proliferative Effects of Insulin on Equine Lamellar Epithelial Cells Mediated By the IGF-1 Receptor

Bailey, S. R.; Chockalingham, S.

doi:10.1016/j.jevs.2010.01.007

Cited by 11 publications

(10 citation statements)

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“…The nuclear localisation of IGF-1R in laminar epithelial cells reported here is consistent with this receptor's documented role in mitogenesis, as nuclear translocation of surface-activated receptor has been reported in both normal and neoplastic cells [30,31]. We also observed a similar surface localisation of IGF-1R in the laminar keratinocyte in vivo as has been reported in cultured equine laminar keratinocytes [32]. Insulin-like growth factor-1 receptor signalling events in the laminar epidermis, particularly its reported effects on regulation of extracellular matrix [33,34], cytoskeletal dynamics [35][36][37], and cellular phenotype [36], may play a role in the dysregulation/dysadhesion of the LBEC from the underlying dermis; further investigation of these signalling events in the LBEC are warranted.…”

Section: Discussionsupporting

confidence: 91%

Distribution of insulin receptor and insulin‐like growth factor‐1 receptor in the digital laminae of mixed‐breed ponies: An immunohistochemical study

Burns

Watts

Weber

et al. 2012

Equine Veterinary Journal

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SummaryReasons for performing study: Hyperinsulinaemia has been implicated in the pathogenesis of laminitis; however, laminar cell types responding to insulin remain poorly characterised. Objectives: To identify laminar cell types expressing insulin receptor (IRc) and/or insulin-like growth factor-1 receptor (IGF-1R); and to evaluate the effect of dietary nonstructural carbohydrate (NSC) on their expression. Methods: Mixed-breed ponies (n = 22) received a conditioning hay chop diet (NSC~6%); following acclimation, ponies were stratified into lean (n = 11, body condition score [BCS] Յ4) or obese (n = 11, BCS Ն7) groups and each group further stratified to remain on the low NSC diet (n = 5 each for obese and lean) or receive a high NSC diet (total diet~42% NSC; n = 6 each for obese and lean) for 7 days. Laminar samples were collected at the end of the feeding protocol and stained immunohistochemically for IRc and IGF-1R. The number of IRc(+) cells was quantified; distribution of IGF-1R was qualitatively described. Laminar IRc content was assessed via immunoblotting. Results: The number of IRc(+) cells was greater in the laminae of high NSC ponies than low NSC ponies (P = 0.001); there was a positive correlation between the change in serum insulin concentration and number of IRc (+)

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Section: Discussionsupporting

confidence: 91%

Distribution of insulin receptor and insulin‐like growth factor‐1 receptor in the digital laminae of mixed‐breed ponies: An immunohistochemical study

Burns

Watts

Weber

et al. 2012

Equine Veterinary Journal

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“…This provides a clue that high concentrations of insulin may in fact be having a direct effect on these key cells. One observation that is consistent with the mitotic figures evident in the lamellar epithelial cells is that insulin has a proliferative effect on these cells in vitro . Although there is no evidence for insulin receptors on these cells, they do express receptors for the insulin‐like growth factor 1 (IGF‐1) .…”

Section: Experimental Models Of Laminitismentioning

confidence: 67%

A review of recent advances and current hypotheses on the pathogenesis of acute laminitis

Katz

Bailey

2012

Equine Veterinary Journal

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SummaryWith the increasing number of studies being published on the different experimental models used to induce and study acute laminitis, the pathophysiological events associated with these various models (i.e. starch overload, oligofructose overload, black walnut extract and hyperinsulinaemia) can be compared more realistically. Within this review, the mechanisms for metabolic vs. inflammatory laminitis are discussed, and the question of how pasture laminitis may fit into any of the proposed mechanisms is addressed.

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“…These similarities mean that there is considerable overlap between the insulin and IGF-1 systems, and although the IGF-1 receptor has an affinity for insulin which is many fold lower than for IGF-1, in many species high concentrations of insulin will bind to and activate the IGF-1 receptor ( Vigneri, Squatrito & Sciacca, 2010 ; De Meyts & Whittaker, 2002 ). In 2009 it was first proposed by Bailey & Chockalingham (2009) that insulin may be capable of stimulating a proliferative response in the lamellar epithelium via the IGF-1 receptor. Burns et al (2013) subsequently found that the IGF-1 receptor was distributed on laminar epidermal epithelial cells as well as dermal vascular cells in ponies fed a high non-structural carbohydrate diet.…”

Section: Introductionmentioning

confidence: 99%

The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor

Baskerville

Chockalingham

Harris³

et al. 2018

PeerJ

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BackgroundIn horses and ponies, insulin dysregulation leading to hyperinsulinemia may be associated with increased risk of laminitis, and prolonged infusion of insulin can induce the condition. It is unclear whether insulin may have a direct or indirect effect on the lamellar tissues. Insulin is structurally related to insulin-like growth factor (IGF-1), and can bind the IGF-1 receptor, albeit at a lower affinity than IGF-1.MethodsImmunohistochemistry was performed on formalin-fixed lamellar tissue sections from six normal horses, euthanised for non-research purposes, using an anti-IGF-1 receptor antibody. In further studies, lamellar epithelial cells were obtained by collagenase digestion from the hooves of 18 normal horses, also euthanised for non-research purposes, and incubated for 48 h in the presence of insulin (0–2,000 m IU/ml). The increase in cell numbers was determined using a cell proliferation assay, and compared to the effect of zero insulin using one-way ANOVA.ResultsImmunohistochemistry demonstrated IGF-1 receptors on lamellar epidermal epithelial cells. With cultured cells, insulin caused a concentration-dependent increase in cell proliferation compared to untreated cells (maximal effect 63.3 ± 12.8% more cells after 48 h with 1,000 m IU/ml insulin; P < 0.01). Co-incubation with a blocking antibody against the IGF-1 receptor significantly inhibited the proliferative effect of insulin (P < 0.01).DiscussionThese results demonstrate that IGF-1 receptors are present on lamellar epithelial cells. At high physiological concentrations, insulin may activate these cells, by a mechanism involving IGF-1 receptors, resulting in a proliferative effect. This mechanism could help to explain the link between hyperinsulinemia and laminitis.

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Proliferative Effects of Insulin on Equine Lamellar Epithelial Cells Mediated By the IGF-1 Receptor

Cited by 11 publications

References 0 publications

Distribution of insulin receptor and insulin‐like growth factor‐1 receptor in the digital laminae of mixed‐breed ponies: An immunohistochemical study

Distribution of insulin receptor and insulin‐like growth factor‐1 receptor in the digital laminae of mixed‐breed ponies: An immunohistochemical study

A review of recent advances and current hypotheses on the pathogenesis of acute laminitis

The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor

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