Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies

Asplin, Katie; Sillence, Martin N.; Pollitt, Christopher C.; McGowan, Catherine

doi:10.1016/j.tvjl.2007.07.003

Cited by 335 publications

(286 citation statements)

References 31 publications

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“…45,46 However, in these experiments, the plasma insulin concentrations that were associated with the development of laminitis significantly exceeded those that are reported for horses and ponies affected with EMS. 45 The fact that insulin can act as an independent trigger factor is important because under certain conditions it might act alongside concurrent trigger factors to cause laminitis at lesser circulating concentrations. Several explanations for a mechanism through which insulin might directly cause laminitis have been suggested and include hoof-lamellar hypoxia associated with insulin-induced microcirculatory dysregulation and increased tissue protease activity (including matrix metalloproteinases), both of which could increase the likelihood of structural failure at the level of the HLI.…”

Section: Recognition and Objective Measurement Of Obesity In Horsescontrasting

confidence: 66%

“…44 Recent experimental work showed that acute laminitis could be directly induced by insulin through maintenance of a supraphysiologic plasma insulin concentration over the course of several days in a euglycemic clamp experiment. 45,46 However, in these experiments, the plasma insulin concentrations that were associated with the development of laminitis significantly exceeded those that are reported for horses and ponies affected with EMS. 45 The fact that insulin can act as an independent trigger factor is important because under certain conditions it might act alongside concurrent trigger factors to cause laminitis at lesser circulating concentrations.…”

contrasting

confidence: 66%

“…Several explanations for a mechanism through which insulin might directly cause laminitis have been suggested and include hoof-lamellar hypoxia associated with insulin-induced microcirculatory dysregulation and increased tissue protease activity (including matrix metalloproteinases), both of which could increase the likelihood of structural failure at the level of the HLI. 45 Although obesity is widely recognized as a risk factor for laminitis, a satisfactory mechanistic explanation is still lacking. 37 Plausible theories include increased weight-bearing, obesity-dependent IR, and the secretion of proinflammatory cytokines by adipose tissue.…”

Section: Pathophysiologymentioning

confidence: 99%

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Laminitis and the Equine Metabolic Syndrome

Johnson

Wiedmeyer

LaCarrubba

et al. 2010

Veterinary Clinics of North America: Equine Practice

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Although much has been written about laminitis in the context of its association with inflammatory processes, such as dietary carbohydrate overload and endotoxemia, [1][2][3][4][5] recognition is growing that most cases of laminitis examined by veterinarians in private practice are those associated with pasture grazing, obesity, and insulin resistance (IR). 6,7 The term endocrinopathic laminitis has been adopted to classify the instances of laminitis in which the origin seems to be more strongly associated with an underlying endocrinopathy, such as either IR or the influence of corticosteroids. [8][9][10][11] Results of a recent study suggest that obesity and IR represent the most common metabolic and endocrinopathic predispositions for laminitis in horses. 6,12 IR also plays an important role in the pathogenesis of laminitis that develops when some horses or ponies are allowed to graze pastures at certain times of the year (pasture-associated laminitis [PAL]). [12][13][14][15] Moreover, IR is provoked by and contributes to pathophysiologic processes associated with endotoxemia and systemic inflammation under the more classic circumstances associated with risk for acute laminitis, such as grain overload, retention of fetal membranes, and gastroenteritis. 16,17 However, a recent study using the oligofructose model showed that experimentally induced laminitis was not associated with a loss of insulin sensitivity. 18 The term equine metabolic syndrome (EMS) has been proposed as a label for horses whose clinical examination results (including both physical examination and laboratory testing) suggest heightened risk for developing laminitis as a result of underlying IR. 19 EMS is not a disease per se, but rather is a clustering of clinical abnormalities that, when identified collectively in a given patient, indicates that the likelihood of developing laminitis is greater than in individuals lacking the EMS criteria. Use of the term EMS is especially practical for distinguishing affected horses from those affected with either Cushing's (pituitary pars intermedia dysfunction [PPID]) or hypothyroidism, with which EMS is often confused. 19 The clinical importance of diagnosing EMS centers on the fact that recognized risk factors for laminitis can subsequently be avoided in the affected individual. Preventive measures aimed at reducing the risk for laminitis should be rigorously emphasized in EMS-affected horses and ponies.Recently, the American College of Veterinary Internal Medicine (ACVIM) commissioned a panel of EMS-interested specialists to develop a consensus statement that would help define the syndrome based on current knowledge. 20 During development of the consensus statement, contents of the working draft were presented and discussed at the ACVIM Annual Forum in Montreal, Canada and some of the following comments will be based on those discussions. 20 Ongoing experimental and clinical studies will help better define EMS (which is distinctly different to the human metabolic syndrome 21 ) in the next few years. D...

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Section: Recognition and Objective Measurement Of Obesity In Horsescontrasting

confidence: 66%

contrasting

confidence: 66%

Section: Pathophysiologymentioning

confidence: 99%

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Laminitis and the Equine Metabolic Syndrome

Johnson

Wiedmeyer

LaCarrubba

et al. 2010

Veterinary Clinics of North America: Equine Practice

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“…Since the first reports of experimental laminitis induction by prolonged systemic insulin and glucose infusion were published,5, 6 much speculation has occurred regarding the most important and relevant pathophysiologic mechanisms by which laminitis develops in this setting. Initial reports suggested that laminar IR may exist, resulting in chronic glucose (carbon substrate) deprivation at the cellular level, energy failure, and dermoepidermal separation (based on in vitro experiments using laminar explants incubated in glucose‐free media for prolonged periods and subjected to mechanical distraction) 2.…”

Section: Discussionmentioning

confidence: 99%

Effect of Dietary Nonstructural Carbohydrate Content on Activation of 5′‐Adenosine Monophosphate‐Activated Protein Kinase in Liver, Skeletal Muscle, and Digital Laminae of Lean and Obese Ponies

Burns

Watts

Weber

et al. 2014

Veterinary Internal Medicne

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BackgroundIn EMS‐associated laminitis, laminar failure may occur in response to energy failure related to insulin resistance (IR) or to the effect of hyperinsulinemia on laminar tissue. 5′‐Adenosine‐monophosphate‐activated protein kinase (AMPK) is a marker of tissue energy deprivation, which may occur in IR.Hypothesis/ObjectivesTo characterize tissue AMPK regulation in ponies subjected to a dietary carbohydrate (CHO) challenge.AnimalsTwenty‐two mixed‐breed ponies.MethodsImmunohistochemistry and immunoblotting for total AMPK and phospho(P)‐AMPK and RT‐qPCR for AMPK‐responsive genes were performed on laminar, liver, and skeletal muscle samples collected after a 7‐day feeding protocol in which ponies stratified on body condition score (BCS; obese or lean) were fed either a low‐CHO diet (ESC + starch, approximately 7% DM; n = 5 obese, 5 lean) or a high‐CHO diet (ESC + starch, approximately 42% DM; n = 6 obese, 6 lean).Results5′‐Adenosine‐monophosphate‐activated protein kinase was immunolocalized to laminar keratinocytes, dermal constituents, and hepatocytes. A high‐CHO diet resulted in significantly decreased laminar [P‐AMPK] in lean ponies (P = .03), but no changes in skeletal muscle (lean, P = .33; obese, P = .43) or liver (lean, P = .84; obese, P = .13) [P‐AMPK]. An inverse correlation existed between [blood glucose] and laminar [P‐AMPK] in obese ponies on a high‐CHO diet.Conclusions and Clinical ImportanceLaminar tissue exhibited a normal response to a high‐CHO diet (decreased [P‐AMPK]), whereas this response was not observed in liver and skeletal muscle in both lean (skeletal muscle, P = .33; liver, P = .84) and obese (skeletal muscle, P = .43; liver, P = .13) ponies.

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“…Horses affected by Cushing's syndrome, obese animals or the ones receiving high and prolonged concentrations of glucocorticoids (RYU et al, 2004, DE LAAT et al, 2010 show endocrine disorders, such as hyperglycemia, hyperinsulinemia and insulin resistance (DE LAAT et al, 2010). The endochrinopathy laminitis is evidenced by milder clinical signs in comparison with laminitis secondary to inflammatory diseases, and in some animals it may occur rotation of the distal phalanx with hoof structural changes, with less intense painful discomfort which can be inconspicuous or absent (JOHNSON, 2002a).…”

Section: Endocrine and Metabolic Mechanismsmentioning

confidence: 99%