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

Background In 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. Methods Immunohistochemistry 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. Results Immunohistochemistry 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). Discussion These 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

Interrogating Whiteness in Community Research and Action

Community psychology is expressly concerned with social justice. Such concern necessitates attention to race. Yet, nearly absent from the field’s literature is explicit and critical attention to whiteness. Thus, community psychology’s contribution to promoting social justice remains incomplete. In this article, we examine how a critical construction of whiteness can be useful for community research and action. After a brief history of the construction of whiteness in the United States, and a summary of key insights from critical whiteness studies, we present a scoping review of the nascent body of community psychology literature that addresses whiteness. That work implicates whiteness in the emergence of the field itself, frames whiteness as social location, problematizes whiteness, addresses White supremacy and institutional racism, interrogates White privilege, and employs whiteness as a theoretical standpoint. We conclude with three propositions for scholars to broker the relationship between community psychology and critical whiteness studies: (a) community psychology should become more critically conscious of whiteness, (b) community psychologists should promote critical awareness of the ways that whiteness operates as a complex system, and (c) greater critical awareness of whiteness should be applied to the development of multilevel interventions aimed at dismantling whiteness as a system of domination

Comparison and validation of ELISA assays for plasma insulin-like growth factor-1 in the horse

Insulin-like growth factor-1 (IGF-1) plays several important physiological roles, and IGF-related pathways have been implicated in developmental osteochondral disease and endocrinopathic laminitis. This factor is also a downstream marker of growth  hormone activity and its peptide mimetics. Unfortunately, previously used assays for measuring equine IGF-1 (radioimmunoassays and ELISAs) are no longer  commercially available, and many of the kits on the market give poor results when  used on horse samples. The aim of the present study was to compare three different ELISA assays (two human and one horse-specific). Plasma samples from six  Standardbreds, six ponies and six Andalusians were used. The human IGF-1 ELISA kit from Immunodiagnostic Systems (IDS) proved to be the most accurate and precise of the three kits; the other two assays gave apparently much lower  concentrations, with poor recovery of spiked recombinant human IGF-1 and unacceptably poor intra-assay coefficients of variation (CV). The IDS assay gave an intra-assay CV of 3.59 % and inter-assay CV of 7.31%. Mean percentage  recovery of spiked IGF-1 was 88.82%, and linearity and dilutional parallelism were satisfied. The IGF-1 plasma concentrations were 123.21 ±8.24 ng/mL for  Standardbreds, 124.95 ±3.69 ng/mL for Andalusians and 174.26 ±1.94 ng/mL for ponies. Therefore of the three assays assessed, the IGF-1 ELISA manufactured by IDS was the most suitable for use with equine plasma samples and may have many useful applications in several different research areas. However, caution should be used when comparing equine studies where different analytical techniques and assays may have been used to measure this growth factor.Keywords: Equine, Insulin-like growth factor, Ponies

Influence of dietary restriction and low‐intensity exercise on weight loss and insulin sensitivity in obese equids

Background The importance of including exercise with dietary modification for the management of obese equids is not clearly understood. Objectives To evaluate the effect of a practical low‐intensity exercise regimen, in addition to dietary restriction, on indices of insulin sensitivity (SI) and plasma adipokine concentrations in obese equids. Animals Twenty‐four obese (body condition score [BCS] ≥ 7/9) horses and ponies. Methods Over a 12‐week period, animals received either dietary restriction only (DIET) or dietary restriction plus low‐intensity exercise (DIET+EX). All animals were provided with a restricted ration of grass hay at 1.25% body weight (BW) on a dry matter basis, providing 82.5% estimated digestible energy requirements. The DIET+EX group undertook low‐intensity exercise 5 days per week on an automated horse walker. Before and after weight loss, total body fat mass (TBFM) was determined, indices of SI were calculated using minimal model analysis of a frequently sampled IV glucose tolerance test, and adipokines plus inflammatory biomarkers were measured using validated assays. Results Decreases in BCS, BW, and TBFM were similar between groups (all P > .05). After weight loss, animals in both groups had decreased basal insulin and leptin concentrations, and increased adiponectin concentrations (all P < .001). Furthermore, animals in the DIET+EX group had significantly improved SI and decreased serum amyloid A concentrations relative to animals in the DIET group (both P = .01). Conclusions and Clinical Importance Regular low‐intensity exercise provided additional health benefits compared with dietary restriction alone in this population of obese equids

Insulin-IGF signaling affects cell transformation in the BALB/c 3T3 cell model

The increased cancer mortality of diabetes type 2 patients is most likely an evidence of the tight connection between tumor development and energy metabolism. A major focus of today’s research is still the identification of key proteins of both diseases and the development of corresponding inhibitors. In this study we combined the two-stage BALB/c-3T3 cell transformation assay (BALB-CTA) with the IR/IGF-1R inhibitor OSI-906 (linsitinib) and analyzed alterations in protein activity and energy parameters in non-transformed as well as transformed cells. OSI-906 successfully inhibited the phosphorylation of IR/IGF-1R and decreased cell growth in non-transformed cells. In the BALB-CTA, a permanent treatment with OSI-906 reduced cellular transformation dose-dependently, whereas a temporary treatment gave evidence for a preventive effect in the promotion phase. Furthermore, even though several key proteins were affected, it was possible to show that the phosphorylation of GSK3, Erk 1/2 and the S6 protein are not crucial for the cell foci reducing effect of OSI-906. Taken together, the BALB-CTA confirmed results of OSI-906 from animal studies and enhanced the knowledge of its mode of action. Therefore, the BALB-CTA offers the opportunity to analyze alterations in the transformation process more precisely and will be helpful to identify effective cancer treatments