Abnormalities of insulin metabolism include hyperinsulinaemia and insulin resistance, and these problems are collectively referred to as insulin dysregulation in this review. Insulin dysregulation is a key component of equine metabolic syndrome: a collection of endocrine and metabolic abnormalities associated with the development of laminitis in horses, ponies and donkeys. Insulin dysregulation can also accompany prematurity and systemic illness in foals. Causes of insulin resistance are discussed, including pathological conditions of obesity, systemic inflammation and pituitary pars intermedia dysfunction, as well as the physiological responses to stress and pregnancy. Most of the discussion of insulin dysregulation to date has focused on insulin resistance, but there is increasing interest in hyperinsulinaemia itself and insulin responses to feeding. An oral sugar test or in-feed oral glucose tolerance test can be performed to assess insulin responses to dietary carbohydrates, and these tests are now recommended for use in clinical practice. Incretin hormones are likely to play an important role in postprandial hyperinsulinaemia and are the subject of current research. Insulin resistance exacerbates hyperinsulinaemia, and insulin sensitivity can be measured by performing a combined glucose-insulin test or i.v. insulin tolerance test. In both of these tests, exogenous insulin is administered and the rate of glucose uptake into tissues measured. Diagnosis and management of hyperinsulinaemia is recommended to reduce the risk of laminitis. The term insulin dysregulation is introduced here to refer collectively to excessive insulin responses to sugars, fasting hyperinsulinaemia and insulin resistance, which are all components of equine metabolic syndrome.

Insulin dysregulation: Insulin dysregulation

Equine metabolic syndrome (EMS) is a widely recognized collection of risk factors for endocrinopathic laminitis. The most important of these risk factors is insulin dysregulation (ID). Clinicians and horse owners must recognize the presence of these risk factors so that they can be targeted and controlled to reduce the risk of laminitis attacks. Diagnosis of EMS is based partly on the horse's history and clinical examination findings, and partly on laboratory testing. Several choices of test exist which examine different facets of ID and other related metabolic disturbances. EMS is controlled mainly by dietary strategies and exercise programs that aim to improve insulin regulation and decrease obesity where present. In some cases, pharmacologic aids might be useful. Management of an EMS case is a long-term strategy requiring diligence and discipline by the horse's carer and support and guidance from their veterinarians.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvim.15423

ECEIM consensus statement on equine metabolic syndrome

Background

Obesity and hyperinsulinemia increase the risk of laminitis in horses and ponies. In mares, obesity also has been associated with increased circulating concentrations of the proinflammatory cytokine, tumor necrosis factor (TNF)-α. The association of other proinflammatory cytokines with body condition score (BCS) and insulin requires further determination.



Hypothesis

Plasma concentrations of TNF, interleukin (IL)-1β, IL-6, and serum amyloid A (SAA) will positively correlate with BCS or insulin or both in horses. Furthermore, inflammatory protein concentrations will correlate with age and variables associated with BCS, including plasma insulin, triglycerides, nonesterified fatty acids, and leptin concentrations.



Animals

One hundred and ten mixed light-breed horses, including mares, geldings, and stallions, aged 4–20 years.



Methods

Samples were selected from a larger population of plasma samples previously collected during June–July of 2006. Samples were analyzed for TNF, IL-1β, IL-6, and SAA using commercially available ELISAs and simple correlations were used to determine relationships with BCS, insulin, age, and sex.



Results

Plasma TNF (P = .047) and IL-6 (P = .021) concentrations were higher in females than males, whereas IL-6 concentrations correlated (P = .001) with age. Plasma SAA concentrations correlated with both insulin (P < .001) and BCS (P = .007).



Conclusions and Clinical Importance

This study provides evidence for factors, including age and sex, that may be associated with plasma concentrations of inflammatory proteins. Concentrations of SAA correlated with BCS and insulin, independent of age or sex. Because BCS and insulin correlate with increased SAA, it is possible that SAA is a component of laminitis pathophysiology.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvim.12021

Relationships between Body Condition Score and Plasma Inflammatory Cytokines, Insulin, and Lipids in a Mixed Population of Light-Breed Horses

The investigation of macromolecular biomolecules with ion mobility mass spectrometry (IM-MS) techniques has provided substantial insights into the field of structural biology over the past two decades. An IM-MS workflow applied to a given target analyte provides mass, charge, and conformation, and all three of these can be used to discern structural information. While mass and charge are determined in mass spectrometry (MS), it is the addition of ion mobility that enables the separation of isomeric and isobaric ions and the direct elucidation of conformation, which has reaped huge benefits for structural biology. In this review, where we focus on the analysis of proteins and their complexes, we outline the typical features of an IM-MS experiment from the preparation of samples, the creation of ions, and their separation in different mobility and mass spectrometers. We describe the interpretation of ion mobility data in terms of protein conformation and how the data can be compared with data from other sources with the use of computational tools. The benefit of coupling mobility analysis to activation via collisions with gas or surfaces or photons photoactivation is detailed with reference to recent examples. And finally, we focus on insights afforded by IM-MS experiments when applied to the study of conformationally dynamic and intrinsically disordered proteins.

https://pubs.acs.org/doi/pdf/10.1021/acs.chemrev.2c00600

Ion Mobility Mass Spectrometry (IM-MS) for Structural Biology: Insights Gained by Measuring Mass, Charge, and Collision Cross Section

The relationships between diet, obesity and insulin dysregulation in equids require further investigation due to their association with laminitis. This study examined the effect of dietary glycaemic load and increased adiposity on insulin sensitivity and adipokine concentrations in different equine breeds. Equal numbers of Standardbred horses, mixed-breed ponies and Andalusian horses were provided with ad libitum hay plus either cereal-rich (CHO; n = 12), fat-rich (FAT; n = 12) or control (CON; n = 9) meals over 20 weeks. The isocaloric CHO and FAT diets were fed to induce obesity by gradually increasing the supplementary feeds to provide 200% of daily digestible energy requirements by Week 20. The CON group were fed a basal ration only and maintained moderate body condition. At Week 20, the CHO and FAT groups demonstrated significantly increased body condition score, bodyweight, total body fat mass and plasma leptin concentrations compared with the CON group (P <0.001). The CHO group had lower insulin sensitivity (SI; P <0.001) and higher acute insulin response to glucose (P = 0.002) than the CON group. In contrast, the FAT group was no different to the control group. Ponies and Andalusians had lower SI values compared with Standardbreds, regardless of diet group (P = 0.001). Adiponectin concentrations were similar between the FAT and CON groups, but were significantly lower in the CHO group (P = 0.010). The provision of cereal-rich meals appeared to be a more important determinant of insulin sensitivity than the induction of obesity per se. Whether hypoadiponectinaemia is a cause or consequence of insulin dysregulation warrants further investigation.

/pdf/effect-of-increased-adiposity-on-insulin-sensitivity-and-rc8g5fvqr3.pdf

Effect of increased adiposity on insulin sensitivity and adipokine concentrations in different equine breeds adapted to cereal-rich or fat-rich meals.

Four experiments were conducted 1) to assess the use of glucose responses to insulin injections as a means of estimating insulin sensitivity in horses and 2) to compare the insulin sensitivities of normal horses vs. those displaying hyperleptinemia (HL). In Exp. 1, HL mares and geldings (n = 4 each) and 4 mares and geldings with normal leptin concentrations (NL) were injected intravenously with 20 and 100 mU/kg of BW of bovine insulin on 2 separate occasions in December 2008. In Exp. 2, the experimental protocol was repeated in late April 2009. In Exp. 1, the 20 mU/kg of BW dose of insulin caused a greater (P 0.1), whereas the greater dose revealed differences (P 0.1) for LL mares, regardless of BCS, and was less (P < 0.01) than for mares with increased leptin concentrations. It was concluded that a dose of 50 mU/kg of BW of recombinant human insulin could be used safely to start the dose-response curve; smaller or larger doses could then be applied as appropriate to get sufficient data for estimation of ED50. Experiment 4, conducted in October of 2009, assessed the repeatability of the estimates for ED50 obtained in Exp. 3. Six mares with LL vs. increased leptin concentrations received the 50 mU/kg dose of insulin; appropriate larger or smaller doses were used to obtain estimates of ED50. Estimates obtained were highly correlated (r = 0.91) with those obtained in Exp. 3, with an average within-mare CV of 8.9%; this is equal to or better than the repeatabilities of the currently used methods of assessing insulin sensitivity in horses. It was concluded that hyperleptinemic horses, which are also hyperinsulinemic and have exaggerated insulin responses to glucose injection, are indeed less sensitive to insulin than normal horses with reduced leptin concentrations of the same body condition.

Hyperleptinemia in mares and geldings: assessment of insulin sensitivity from glucose responses to insulin injection.

Mechanistic understanding of metal-catalyzed oxidation of polysorbate 80 and monoclonal antibody in biotherapeutic formulations.

Evaluation of the Combined Intravenous Glucose and Insulin Test for Assessing Insulin Sensitivity

Estradiol stimulation of prolactin secretion in horses: Interaction with type of secretagogue

Is the Stimulatory Effect of Estradiol on Prolactin Secretion Mediated by a Change in Dopaminergic Input to the Pituitary

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