A review of recent developments in the pharmacological prevention and treatment of endocrinopathic laminitis
M. A. de Laat A B and M. N. Sillence AA Biology and Environmental Science, Science and Engineering Faculty, Queensland University of Technology, 2 George Street, Gardens Point, Brisbane, Qld 4001, Australia.
B Corresponding author. Email: melody.delaat@qut.edu.au
Animal Production Science 60(18) 2111-2121 https://doi.org/10.1071/AN19491
Submitted: 30 August 2019 Accepted: 22 April 2020 Published: 16 June 2020
Journal Compilation © CSIRO 2020 Open Access CC BY-NC
Abstract
Despite the prevalence of endocrinopathic laminitis, the pharmacologic options for preventing and treating the disease are severely limited. The present review aims to discuss the spectrum of potential therapeutic agents for the condition, ranging from early experimental compounds to agents nearing registration. There are different pharmacologic targets for, and approaches to, managing laminitis. Reducing hyperinsulinaemia is central to diminishing endocrinopathic laminitis risk, and a detailed understanding of the pathophysiology of insulin dysregulation is necessary to identify pathways that can be targeted to minimise post-prandial insulin secretion and action. This area of research is advancing rapidly, with several exciting prospects, such as sodium-dependent glucose co-transporter-2 inhibitors, on the horizon for the treatment of equine metabolic dysfunction. Drugs that directly target the lamellae and aim to reduce the damage inflicted on the lamellae as part of this condition, are not yet available. Although progress in this area of laminitis therapy is slower, improved understanding of the events that lead to lamellar failure has enabled the investigation of novel drugs that aim to prevent laminitis at the site of the lesion. Finally, a brief review is included of the directions being taken in the management of the chronic and acute pain that accompanies laminitis. Medications for relieving the pain associated with laminitis are currently the most-prescribed drugs for the disease, and range from simple, affordable and thoroughly tested options, such as phenylbutazone, to newer, less-understood applications such as paracetamol and gabapentin. In the future, endocrinopathic laminitis management plans will likely take a multi-faceted approach that still hinge on effective dietary management and exercise, but also include drugs that address foot pathology, pain and underlying endocrine disturbances.
Additional keywords: equine metabolic syndrome, horse, hyperinsulinaemia, insulin dysregulation, lamellae, pituitary pars intermedia dysfunction.
References
Asplin KE, Sillence MN, Pollitt CC, McGowan CM (2007) Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies. Veterinary Journal 174, 530–535.| Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies.Crossref | GoogleScholarGoogle Scholar |
Bailey SR, Baillon ML, Rycroft AN, Harris PA, Elliott J (2003) Identification of equine cecal bacteria producing amines in an in vitro model of carbohydrate overload. Applied and Environmental Microbiology 69, 2087–2093.
| Identification of equine cecal bacteria producing amines in an in vitro model of carbohydrate overload.Crossref | GoogleScholarGoogle Scholar | 12676687PubMed |
Bailey SR, Menzies-Gow NJ, Marr CM, Elliott J (2004) The effects of vasoactive amines found in the equine hindgut on digital blood flow in the normal horse. Equine Veterinary Journal 36, 267–272.
| The effects of vasoactive amines found in the equine hindgut on digital blood flow in the normal horse.Crossref | GoogleScholarGoogle Scholar | 15147136PubMed |
Bamford NJ, Baskerville CL, Harris PA, Bailey SR (2015) Postprandial glucose, insulin, and glucagon-like peptide-1 responses of different equine breeds adapted to meals containing micronized maize. Journal of Animal Science 93, 3377–3383.
| Postprandial glucose, insulin, and glucagon-like peptide-1 responses of different equine breeds adapted to meals containing micronized maize.Crossref | GoogleScholarGoogle Scholar | 26440006PubMed |
Banse H, Cribb AE (2017) Comparative efficacy of oral meloxicam and phenylbutazone in 2 experimental pain models in the horse The Canadian Veterinary Journal. La Revue Veterinaire Canadienne 58, 157–167.
Bar RS, Boes M (1984) Distinct receptors for IGF-I, IGF-II, and insulin are present on bovine capillary endothelial cells and large vessel endothelial cells. Biochemical and Biophysical Research Communications 124, 203–209.
| Distinct receptors for IGF-I, IGF-II, and insulin are present on bovine capillary endothelial cells and large vessel endothelial cells.Crossref | GoogleScholarGoogle Scholar | 6093785PubMed |
Baskerville CL, Chockalingham S, Harris PA, Bailey SR (2018) The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor. PeerJ 6, e5945
| The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor.Crossref | GoogleScholarGoogle Scholar | 30519508PubMed |
Bays H (2013) Sodium glucose co-transporter type 2 (SGLT2) inhibitors: targeting the kidney to improve glycemic control in diabetes mellitus. Diabetes Therapy: Research, Treatment and Education of Diabetes and Related Disorders 4, 195–220.
| Sodium glucose co-transporter type 2 (SGLT2) inhibitors: targeting the kidney to improve glycemic control in diabetes mellitus.Crossref | GoogleScholarGoogle Scholar |
Beckwith H, Yee D (2015) Minireview: were the IGF signaling inhibitors all bad? Molecular Endocrinology 29, 1549–1557.
| Minireview: were the IGF signaling inhibitors all bad?Crossref | GoogleScholarGoogle Scholar | 26366975PubMed |
Belknap JK (2016) ‘Laminitis in horses.’ Available at https://www.msdvetmanual.com/musculoskeletal-system/lameness-in-horses/laminitis-in-horses [Verified September 2015]
Beretta C, Garavaglia G, Cavalli M (2005) COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis. Pharmacological Research 52, 302–306.
| COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis.Crossref | GoogleScholarGoogle Scholar | 15939622PubMed |
Berhane Y, Bailey SR, Putignano C, Elliott J (2008) Characterization of agonist-induced endothelium-dependent vasodilatory responses in the vascular bed of the equine digit. Journal of Veterinary Pharmacology and Therapeutics 31, 1–8.
Blau JE, Taylor SI (2018) Adverse effects of SGLT2 inhibitors on bone health. Nature Reviews. Nephrology 14, 473–474.
| Adverse effects of SGLT2 inhibitors on bone health.Crossref | GoogleScholarGoogle Scholar | 29875481PubMed |
Bloomgarden ZT (1998) Insulin resistance: current concepts. Clinical Therapeutics 20, 216–231.
| Insulin resistance: current concepts.Crossref | GoogleScholarGoogle Scholar | 9589814PubMed |
Blum G, Gazit A, Levitzki A (2000) Substrate competitive inhibitors of IGF-1 receptor kinase. Biochemistry 39, 15705–15712.
| Substrate competitive inhibitors of IGF-1 receptor kinase.Crossref | GoogleScholarGoogle Scholar | 11123895PubMed |
Bravo L, Mico JA, Berrocoso E (2017) Discovery and development of tramadol for the treatment of pain. Expert Opinion on Drug Discovery 12, 1281–1291.
| Discovery and development of tramadol for the treatment of pain.Crossref | GoogleScholarGoogle Scholar | 28920461PubMed |
Burns TA, Watts MR, Weber PS, McCutcheon LJ, Geor RJ, Belknap JK (2013) Distribution of insulin receptor and insulin-like growth factor-1 receptor in the digital laminae of mixed-breed ponies: an immunohistochemical study. Equine Veterinary Journal 45, 326–332.
| Distribution of insulin receptor and insulin-like growth factor-1 receptor in the digital laminae of mixed-breed ponies: an immunohistochemical study.Crossref | GoogleScholarGoogle Scholar | 22924550PubMed |
Cahn A, Cefalu WT (2016) Clinical considerations for use of initial combination therapy in type 2 diabetes. Diabetes Care 39, S137–S145.
| Clinical considerations for use of initial combination therapy in type 2 diabetes.Crossref | GoogleScholarGoogle Scholar | 27440826PubMed |
Cárceles-Rodríguez CM, Fernandez-Varon E, Martin-Gimenez T, Aguirre C, Arion A, Rodriguez MJ, Ayala I (2019) Pharmacokinetics of metformin in combination with sitagliptin in adult horses after enteral administration. Journal of Equine Veterinary Science 72, 84–88.
| Pharmacokinetics of metformin in combination with sitagliptin in adult horses after enteral administration.Crossref | GoogleScholarGoogle Scholar | 30929789PubMed |
Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, Freeman R, Truini A, Attal N, Finnerup NB, Eccleston C, Kalso E, Bennett DL, Dworkin RH, Raja SN (2017) Neuropathic pain. Nature Reviews. Disease Primers 3, 17002
| Neuropathic pain.Crossref | GoogleScholarGoogle Scholar | 28205574PubMed |
Daly K, Al-Rammahi M, Arora DK, Moran AW, Proudman CJ, Ninomiya Y, Shirazi-Beechey SP (2012) Expression of sweet receptor components in equine small intestine: relevance to intestinal glucose transport. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 303, R199–R208.
| Expression of sweet receptor components in equine small intestine: relevance to intestinal glucose transport.Crossref | GoogleScholarGoogle Scholar | 22552794PubMed |
de Laat MA, McGowan CM, Sillence MN, Pollitt CC (2010) Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses. Equine Veterinary Journal 42, 129–135.
| Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses.Crossref | GoogleScholarGoogle Scholar | 20156248PubMed |
de Laat MA, Kyaw-Tanner MT, Nourian AR, McGowan CM, Sillence MN, Pollitt CC (2011) The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity. Veterinary Immunology and Immunopathology 140, 275–281.
| The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity.Crossref | GoogleScholarGoogle Scholar | 21333362PubMed |
de Laat MA, Pollitt CC, Walsh DM, McGowan CM, Sillence MN (2012) Persistent digital hyperthermia over a 48 h period does not induce laminitis in horses. Veterinary Journal 192, 435–440.
| Persistent digital hyperthermia over a 48 h period does not induce laminitis in horses.Crossref | GoogleScholarGoogle Scholar |
de Laat MA, Patterson-Kane JC, Pollitt CC, Sillence MN, McGowan CM (2013a) Histological and morphometric lesions in the pre-clinical, developmental phase of insulin-induced laminitis in Standardbred horses. Veterinary Journal 195, 305–312.
| Histological and morphometric lesions in the pre-clinical, developmental phase of insulin-induced laminitis in Standardbred horses.Crossref | GoogleScholarGoogle Scholar |
de Laat MA, Pollitt CC, Kyaw-Tanner MT, McGowan CM, Sillence MN (2013b) A potential role for lamellar insulin-like growth factor-1 receptor in the pathogenesis of hyperinsulinaemic laminitis. Veterinary Journal 197, 302–306.
| A potential role for lamellar insulin-like growth factor-1 receptor in the pathogenesis of hyperinsulinaemic laminitis.Crossref | GoogleScholarGoogle Scholar |
de Laat MA, McGree JM, Sillence MN (2016) Equine hyperinsulinemia: investigation of the enteroinsular axis during insulin dysregulation. American Journal of Physiology. Endocrinology and Metabolism 310, E61–E72.
| Equine hyperinsulinemia: investigation of the enteroinsular axis during insulin dysregulation.Crossref | GoogleScholarGoogle Scholar | 26530154PubMed |
de Laat MA, Fitzgerald DM, Sillence MN, Spence RJ (2018a) Glucagon-like peptide-2: a potential role in equine insulin dysregulation. Equine Veterinary Journal 50, 842–847.
| Glucagon-like peptide-2: a potential role in equine insulin dysregulation.Crossref | GoogleScholarGoogle Scholar | 29502360PubMed |
de Laat MA, Kheder MH, Pollitt CC, Sillence MN (2018b) Sweet taste receptor inhibitors: potential treatment for equine insulin dysregulation. PLoS One 13, e0200070
| Sweet taste receptor inhibitors: potential treatment for equine insulin dysregulation.Crossref | GoogleScholarGoogle Scholar | 29958298PubMed |
Ding H, Gao XL, Hirschberg R, Vadgama JV, Kopple JD (1996) Impaired actions of insulin-like growth factor 1 on protein synthesis and degradation in skeletal muscle of rats with chronic renal failure. Evidence for a postreceptor defect. The Journal of Clinical Investigation 97, 1064–1075.
| Impaired actions of insulin-like growth factor 1 on protein synthesis and degradation in skeletal muscle of rats with chronic renal failure. Evidence for a postreceptor defect.Crossref | GoogleScholarGoogle Scholar | 8613530PubMed |
Donaldson MT, LaMonte BH, Morresey P, Smith G, Beech J (2002) Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushing’s disease). Journal of Veterinary Internal Medicine 16, 742–746.
Durham AE, Rendle DI, Newton JR (2008) The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance. Equine Veterinary Journal 40, 493–500.
| The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance.Crossref | GoogleScholarGoogle Scholar | 18482898PubMed |
Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, Feige K, Fey K (2019) ECEIM consensus statement on equine metabolic syndrome. Journal of Veterinary Internal Medicine 33, 335–349.
| ECEIM consensus statement on equine metabolic syndrome.Crossref | GoogleScholarGoogle Scholar | 30724412PubMed |
Duz M, Marshall JF, Parkin TD (2019) Proportion of nonsteroidal anti-inflammatory drug prescription in equine practice. Equine Veterinary Journal 51, 147–153.
| Proportion of nonsteroidal anti-inflammatory drug prescription in equine practice.Crossref | GoogleScholarGoogle Scholar | 30048005PubMed |
Eades SC, Stokes AM, Johnson PJ, LeBlanc CJ, Ganjam VK, Buff PR, Moore RM (2007) Serial alterations in digital hemodynamics and endothelin-1 immunoreactivity, platelet-neutrophil aggregation, and concentrations of nitric oxide, insulin, and glucose in blood obtained from horses following carbohydrate overload. American Journal of Veterinary Research 68, 87–94.
| Serial alterations in digital hemodynamics and endothelin-1 immunoreactivity, platelet-neutrophil aggregation, and concentrations of nitric oxide, insulin, and glucose in blood obtained from horses following carbohydrate overload.Crossref | GoogleScholarGoogle Scholar | 17199424PubMed |
Everts B, Wahrborg P, Hedner T (2000) COX-2-specific inhibitors: the emergence of a new class of analgesic and anti-inflammatory drugs. Clinical Rheumatology 19, 331–343.
| COX-2-specific inhibitors: the emergence of a new class of analgesic and anti-inflammatory drugs.Crossref | GoogleScholarGoogle Scholar | 11055820PubMed |
Fitzgerald DM, de Laat MA, Harris PA, Bailey SR (2018) Effect on plasma insulin of a peptide inhibitor of the incretin hormone, GLP-1, in ponies fed a meal containing micronized maize. In ‘Australasian equine science symposium’, Gold Coast, Qld, Australia.
Foreman JH (2019) ‘Hyperlipemia and hepatic lipidosis in large animals.’ Available at https:// https://www.msdvetmanual.com/digestive-system/hepatic-disease-in-large-animals/hyperlipemia-and-hepatic-lipidosis-in-large-animals [Verified August 2014]
Frank N (2018) Safety and efficacy of canagliflozin and octreotide for managing insulin dysregulation in horses. Journal of Veterinary Internal Medicine 32, 2123–2143.
Garcia-Ropero A, Badimon JJ, Santos-Gallego CG (2018) The pharmacokinetics and pharmacodynamics of SGLT2 inhibitors for type 2 diabetes mellitus: the latest developments. Expert Opinion on Drug Metabolism & Toxicology 14, 1287–1302.
| The pharmacokinetics and pharmacodynamics of SGLT2 inhibitors for type 2 diabetes mellitus: the latest developments.Crossref | GoogleScholarGoogle Scholar |
Guedes AG, Matthews NS, Hood DM (2012) Effect of ketamine hydrochloride on the analgesic effects of tramadol hydrochloride in horses with signs of chronic laminitis-associated pain. American Journal of Veterinary Research 73, 610–619.
| Effect of ketamine hydrochloride on the analgesic effects of tramadol hydrochloride in horses with signs of chronic laminitis-associated pain.Crossref | GoogleScholarGoogle Scholar | 22533391PubMed |
Guedes A, Knych H, Hood D (2016) Plasma concentrations, analgesic and physiological assessments in horses with chronic laminitis treated with two doses of oral tramadol. Equine Veterinary Journal 48, 528–531.
| Plasma concentrations, analgesic and physiological assessments in horses with chronic laminitis treated with two doses of oral tramadol.Crossref | GoogleScholarGoogle Scholar | 25832551PubMed |
Haluska P, Worden F, Olmos D, Yin DH, Schteingart D, Batzel GN, Paccagnella ML, de Bono JS, Gualberto A, Hammer GD (2010) Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma. Cancer Chemotherapy and Pharmacology 65, 765–773.
| Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma.Crossref | GoogleScholarGoogle Scholar | 19649631PubMed |
Hoenig M, Clark M, Schaeffer DJ, Reiche D (2018) Effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor velagliflozin, a new drug with therapeutic potential to treat diabetes in cats. Journal of Veterinary Pharmacology and Therapeutics 41, 266–273.
| Effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor velagliflozin, a new drug with therapeutic potential to treat diabetes in cats.Crossref | GoogleScholarGoogle Scholar | 29139146PubMed |
Hoff TK, Hood DM, Wagner IR (2002) Effectiveness of glyceryl trinitrate for enhancing digital submural perfusion in horses. American Journal of Veterinary Research 63, 648–652.
| Effectiveness of glyceryl trinitrate for enhancing digital submural perfusion in horses.Crossref | GoogleScholarGoogle Scholar | 12013463PubMed |
Hood DM, Wagner IP, Brumbaugh GW (2001) Evaluation of hoof wall surface temperature as an index of digital vascular perfusion during the prodromal and acute phases of carbohydrate-induced laminitis in horses. American Journal of Veterinary Research 62, 1167–1172.
| Evaluation of hoof wall surface temperature as an index of digital vascular perfusion during the prodromal and acute phases of carbohydrate-induced laminitis in horses.Crossref | GoogleScholarGoogle Scholar | 11453497PubMed |
Hustace JL, Firshman AM, Mata JE (2009) Pharmacokinetics and bioavailability of metformin in horses. American Journal of Veterinary Research 70, 665–668.
| Pharmacokinetics and bioavailability of metformin in horses.Crossref | GoogleScholarGoogle Scholar | 19405907PubMed |
Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, Kim HH, Xu X, Chan SL, Juhaszova M, Bernier M, Mosinger B, Margolskee RF, Egan JM (2007) Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proceedings of the National Academy of Sciences of the United States of America 104, 15 069–15 074.
| Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1.Crossref | GoogleScholarGoogle Scholar |
Jones E, Vinuela-Fernandez I, Eager RA, Delaney A, Anderson H, Patel A, Robertson DC, Allchorne A, Sirinathsinghji EC, Milne EM, MacIntyre N, Shaw DJ, Waran NK, Mayhew J, Fleetwood-Walker SM (2007) Neuropathic changes in equine laminitis pain. Pain 132, 321–331.
| Neuropathic changes in equine laminitis pain.Crossref | GoogleScholarGoogle Scholar | 17935886PubMed |
Joost H-G, Thorens B (2001) The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members. Molecular Membrane Biology 18, 247–256.
| The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members.Crossref | GoogleScholarGoogle Scholar | 11780753PubMed |
Karikoski NP, Horn I, McGowan TW, McGowan CM (2011) The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first-opinion/referral equine hospital. Domestic Animal Endocrinology 41, 111–117.
| The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first-opinion/referral equine hospital.Crossref | GoogleScholarGoogle Scholar | 21696910PubMed |
Karikoski NP, McGowan CM, Singer ER, Asplin KE, Tulamo RM, Patterson-Kane JC (2015) Pathology of natural cases of equine endocrinopathic laminitis associated with hyperinsulinemia. Veterinary Pathology 52, 945–956.
| Pathology of natural cases of equine endocrinopathic laminitis associated with hyperinsulinemia.Crossref | GoogleScholarGoogle Scholar | 25232034PubMed |
Keen JA, McLaren M, Chandler KJ, McGorum BC (2004) Biochemical indices of vascular function, glucose metabolism and oxidative stress in horses with equine Cushing’s disease. Equine Veterinary Journal 36, 226–229.
| Biochemical indices of vascular function, glucose metabolism and oxidative stress in horses with equine Cushing’s disease.Crossref | GoogleScholarGoogle Scholar | 15147129PubMed |
Kheder MH, Bailey SR, Dudley KJ, Sillence MN, de Laat MA (2018) Equine glucagon-like peptide-1 receptor physiology. PeerJ 6, e4316
| Equine glucagon-like peptide-1 receptor physiology.Crossref | GoogleScholarGoogle Scholar | 29404215PubMed |
Knowles EJ (2019) Does pergolide therapy prevent laminitis in horses diagnosed with pituitary pars intermedia dysfunction? Equine Veterinary Education 31, 278–280.
| Does pergolide therapy prevent laminitis in horses diagnosed with pituitary pars intermedia dysfunction?Crossref | GoogleScholarGoogle Scholar |
Kyaw-Tanner M, Pollitt CC (2004) Equine laminitis: increased transcription of matrix metalloproteinase-2 (MMP-2) occurs during the developmental phase. Equine Veterinary Journal 36, 221–225.
| Equine laminitis: increased transcription of matrix metalloproteinase-2 (MMP-2) occurs during the developmental phase.Crossref | GoogleScholarGoogle Scholar | 15147128PubMed |
Levionnois OL, Graubner C, Spadavecchia C (2018) Colon constipation in horses after sustained-release buprenorphine administration. Veterinary Anaesthesia and Analgesia 45, 876–880.
| Colon constipation in horses after sustained-release buprenorphine administration.Crossref | GoogleScholarGoogle Scholar | 30297131PubMed |
Liang Y, Arakawa K, Ueta K, Matsushita Y, Kuriyama C, Martin T, Du F, Liu Y, Xu J, Conway B, Conway J, Polidori D, Ways K, Demarest K (2012) Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models. PLoS One 7, e30555
| Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models.Crossref | GoogleScholarGoogle Scholar | 23272189PubMed |
List JF, Whaley JM (2011) Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans. Kidney International 79, S20–S27.
| Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans.Crossref | GoogleScholarGoogle Scholar |
Malone E, Ensink J, Turner T, Wilson J, Andrews F, Keegan K, Lumsden J (2006) Intravenous continuous infusion of lidocaine for treatment of equine ileus. Veterinary Surgery 35, 60–66.
| Intravenous continuous infusion of lidocaine for treatment of equine ileus.Crossref | GoogleScholarGoogle Scholar | 16409411PubMed |
Markowicz-Piasecka M, Huttunen KM, Mateusiak L, Mikiciuk-Olasik E, Sikora J (2017) Is metformin a perfect drug? Updates in pharmacokinetics and pharmacodynamics. Current Pharmaceutical Design 23, 2532–2550.
| Is metformin a perfect drug? Updates in pharmacokinetics and pharmacodynamics.Crossref | GoogleScholarGoogle Scholar | 27908266PubMed |
Masic D, Liang E, Long C, Sterk EJ, Barbas B, Rech MA (2018) Intravenous lidocaine for acute pain: a systematic review. Pharmacotherapy 38, 1250–1259.
| Intravenous lidocaine for acute pain: a systematic review.Crossref | GoogleScholarGoogle Scholar | 30303542PubMed |
McCreight LJ, Bailey CJ, Pearson ER (2016) Metformin and the gastrointestinal tract. Diabetologia 59, 426–435.
| Metformin and the gastrointestinal tract.Crossref | GoogleScholarGoogle Scholar | 26780750PubMed |
McFarlane D (2011) Equine pituitary pars intermedia dysfunction. The Veterinary Clinics of North America. Equine Practice 27, 93–113.
| Equine pituitary pars intermedia dysfunction.Crossref | GoogleScholarGoogle Scholar | 21392656PubMed |
Meier A, Reiche D, de Laat M, Pollitt C, Walsh D, Sillence M (2018a) The sodium–glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies. PLoS One 13, e0203655
| The sodium–glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies.Crossref | GoogleScholarGoogle Scholar | 30359368PubMed |
Meier AD, de Laat MA, Reiche DB, Pollitt CC, Walsh DM, McGree JM, Sillence MN (2018b) The oral glucose test predicts laminitis risk in ponies fed a diet high in nonstructural carbohydrates. Domestic Animal Endocrinology 63, 1–9.
| The oral glucose test predicts laminitis risk in ponies fed a diet high in nonstructural carbohydrates.Crossref | GoogleScholarGoogle Scholar | 29172109PubMed |
Meier A, de Laat M, Reiche D, Fitzgerald D, Sillence M (2019) The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies. BMC Veterinary Research 15, 65
| The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies.Crossref | GoogleScholarGoogle Scholar | 30808423PubMed |
Mercer MA, McKenzie HC, Davis JL, Wilson KE, Hodgson DR, Cecere TE, McIntosh BJ (2020) Pharmacokinetics and safety of repeated oral dosing of acetaminophen in adult horses. Equine Veterinary Journal 52, 120–125.
| Pharmacokinetics and safety of repeated oral dosing of acetaminophen in adult horses.Crossref | GoogleScholarGoogle Scholar | 30900298PubMed |
Morgan RA, Keen JA, McGowan CM (2016) Treatment of equine metabolic syndrome: a clinical case series. Equine Veterinary Journal 48, 422–426.
| Treatment of equine metabolic syndrome: a clinical case series.Crossref | GoogleScholarGoogle Scholar | 25808563PubMed |
Morgan RA, Keen JA, Walker BR, Hadoke PW (2016) Vascular dysfunction in horses with endocrinopathic laminitis. PLoS One 11, e0163815
| Vascular dysfunction in horses with endocrinopathic laminitis.Crossref | GoogleScholarGoogle Scholar | 27684374PubMed |
Morgan J, Stefanovski D, Lenfest M, Chatterjee S, Orsini J (2018) Novel dry cryotherapy system for cooling the equine digit. Veterinary Record Open 5, e000244
| Novel dry cryotherapy system for cooling the equine digit.Crossref | GoogleScholarGoogle Scholar | 29344364PubMed |
Nakamura M, Chikama TI, Nishida T (2000) Characterization of insulin-like growth factor-1 receptors in rabbit corneal epithelial cells. Experimental Eye Research 70, 199–204.
| Characterization of insulin-like growth factor-1 receptors in rabbit corneal epithelial cells.Crossref | GoogleScholarGoogle Scholar | 10655145PubMed |
Nanayakkara SN, Rahnama S, Harris PA, Anderson ST, de Laat MA, Bailey S, Sillence MN (2019) Characterization of insulin and IGF-1 receptor binding in equine liver and lamellar tissue: implications for endocrinopathic laminitis. Domestic Animal Endocrinology 66, 21–26.
| Characterization of insulin and IGF-1 receptor binding in equine liver and lamellar tissue: implications for endocrinopathic laminitis.Crossref | GoogleScholarGoogle Scholar | 30205269PubMed |
Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR (2017) Canagliflozin and cardiovascular and renal events in type 2 diabetes. The New England Journal of Medicine 377, 644–657.
| Canagliflozin and cardiovascular and renal events in type 2 diabetes.Crossref | GoogleScholarGoogle Scholar | 28605608PubMed |
Neirinckx E, Vervaet C, De Boever S, Remon JP, Gommeren K, Daminet S, De Backer P, Croubels S (2010) Species comparison of oral bioavailability, first-pass metabolism and pharmacokinetics of acetaminophen. Research in Veterinary Science 89, 113–119.
| Species comparison of oral bioavailability, first-pass metabolism and pharmacokinetics of acetaminophen.Crossref | GoogleScholarGoogle Scholar | 20211479PubMed |
Neumiller JJ (2014) Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. Drugs in Context 3, 212262
Nguyen CA, Akiba Y, Kaunitz JD (2012) Recent advances in gut nutrient chemosensing. Current Medicinal Chemistry 19, 28–34.
| Recent advances in gut nutrient chemosensing.Crossref | GoogleScholarGoogle Scholar | 22300073PubMed |
Opie LH (2014) Sodium glucose co-transporter 2 (SGLT2) inhibitors: new among antidiabetic drugs. Cardiovascular Drugs and Therapy 28, 331–334.
| Sodium glucose co-transporter 2 (SGLT2) inhibitors: new among antidiabetic drugs.Crossref | GoogleScholarGoogle Scholar | 24825435PubMed |
Poirée JC, Vannier C, Sudaka P, Fehlmann M (1978) Glucose transport by horse kidney brush borders. I. Transport properties of brush border membrane closed vesicles. Biochimie 60, 645–651.
| Glucose transport by horse kidney brush borders. I. Transport properties of brush border membrane closed vesicles.Crossref | GoogleScholarGoogle Scholar | 719044PubMed |
Pollitt CC (2004) Equine laminitis. Clinical Techniques in Equine Practice 3, 34–44.
| Equine laminitis.Crossref | GoogleScholarGoogle Scholar |
Pollitt CC, Davies CT (1998) Equine laminitis: its development coincides with increased sublamellar blood flow. Equine Veterinary Journal 30, 125–132.
| Equine laminitis: its development coincides with increased sublamellar blood flow.Crossref | GoogleScholarGoogle Scholar |
Pollitt CC, Pass MA, Pollitt S (1998) Batimastat (BB-94) inhibits matrix metalloproteinases of equine laminitis. Equine Veterinary Journal 30, 119–124.
| Batimastat (BB-94) inhibits matrix metalloproteinases of equine laminitis.Crossref | GoogleScholarGoogle Scholar |
Proctor-Brown L, Hicks R, Colmer S, Guilfoyle D, Dallap-Schaer B, Johnson AL, Tomlinson J (2018) Distal limb pathologic conditions in horses treated with sleeve-style digital cryotherapy (285 cases). Research in Veterinary Science 121, 12–17.
| Distal limb pathologic conditions in horses treated with sleeve-style digital cryotherapy (285 cases).Crossref | GoogleScholarGoogle Scholar | 30308395PubMed |
Rendle DI, Rutledge F, Hughes KJ, Heller J, Durham AE (2013) Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses. Equine Veterinary Journal 45, 751–754.
| Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses.Crossref | GoogleScholarGoogle Scholar | 23600690PubMed |
Risberg A, Spadavecchia C, Ranheim B, Krontveit R, Haga HA (2014) Antinociceptive effects of three escalating dexmedetomidine and lignocaine constant rate infusions in conscious horses. Veterinary Journal 202, 489–497.
| Antinociceptive effects of three escalating dexmedetomidine and lignocaine constant rate infusions in conscious horses.Crossref | GoogleScholarGoogle Scholar |
Rosenwasser RF, Sultan S, Sutton D, Choksi R, Epstein BJ (2013) SGLT-2 inhibitors and their potential in the treatment of diabetes. Diabetes, Metabolic Syndrome and Obesity 6, 453–467.
Sanchez LC, Robertson SA (2014) Pain control in horses: what do we really know? Equine Veterinary Journal 46, 517–523.
| Pain control in horses: what do we really know?Crossref | GoogleScholarGoogle Scholar | 24645799PubMed |
Santer R, Calado J (2010) Familial renal glucosuria and SGLT2: from a mendelian trait to a therapeutic target. Clinical Journal of the American Society of Nephrology; CJASN 5, 133–141.
| Familial renal glucosuria and SGLT2: from a mendelian trait to a therapeutic target.Crossref | GoogleScholarGoogle Scholar | 19965550PubMed |
Savides MC, Oehme FW, Nash SL, Leipold HW (1984) The toxicity and biotransformation of single doses of acetaminophen in dogs and cats. Toxicology and Applied Pharmacology 74, 26–34.
| The toxicity and biotransformation of single doses of acetaminophen in dogs and cats.Crossref | GoogleScholarGoogle Scholar | 6729821PubMed |
Schatzmann U, Gugelmann M, Von Cranach J, Ludwig BM, Rehm WF (1990) Pharmacodynamic evaluation of the peripheral pain inhibition by carprofen and flunixin in the horse. Schweizer Archiv fur Tierheilkunde 132, 497–504.
Shilo Y, Britzi M, Eytan B, Lifschitz T, Soback S, Steinman A (2008) Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration. Journal of Veterinary Pharmacology and Therapeutics 31, 60–65.
| Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration.Crossref | GoogleScholarGoogle Scholar | 18177320PubMed |
Sibbald B (2004) Rofecoxib (Vioxx) voluntarily withdrawn from market. Canadian Medical Association Journal 171, 1027–1028.
| Rofecoxib (Vioxx) voluntarily withdrawn from market.Crossref | GoogleScholarGoogle Scholar | 15505253PubMed |
Sigoillot M, Brockhoff A, Meyerhof W, Briand L (2012) Sweet-taste-suppressing compounds: current knowledge and perspectives of application. Applied Microbiology and Biotechnology 96, 619–630.
| Sweet-taste-suppressing compounds: current knowledge and perspectives of application.Crossref | GoogleScholarGoogle Scholar | 22983596PubMed |
Soos MA, Siddle K (1989) Immunological relationships between receptors for insulin and insulin-like growth factor I. Evidence for structural heterogeneity of insulin-like growth factor I receptors involving hybrids with insulin receptors. The Biochemical Journal 263, 553–563.
| Immunological relationships between receptors for insulin and insulin-like growth factor I. Evidence for structural heterogeneity of insulin-like growth factor I receptors involving hybrids with insulin receptors.Crossref | GoogleScholarGoogle Scholar | 2480779PubMed |
Tavanaeimanesh H, Azarnoosh A, Ashar FS, Dehghan MM, Mohebbi Z, Akbarinejad V, Corley K (2018) Comparison of analgesic effects of a constant rate infusion of both tramadol and acetaminophen versus those of infusions of each individual drug in horses. Journal of Equine Veterinary Science 64, 101–106.
| Comparison of analgesic effects of a constant rate infusion of both tramadol and acetaminophen versus those of infusions of each individual drug in horses.Crossref | GoogleScholarGoogle Scholar | 30973144PubMed |
Terry RL, McDonnell SM, Van Eps AW, Soma LR, Liu Y, Uboh CE, Moate PJ, Driessen B (2010) Pharmacokinetic profile and behavioral effects of gabapentin in the horse. Journal of Veterinary Pharmacology and Therapeutics 33, 485–494.
| Pharmacokinetic profile and behavioral effects of gabapentin in the horse.Crossref | GoogleScholarGoogle Scholar | 20840393PubMed |
Thomas MC, Cherney DZI (2018) The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure. Diabetologia 61, 2098–2107.
| The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure.Crossref | GoogleScholarGoogle Scholar | 30132034PubMed |
Tinworth KD, Boston RC, Harris PA, Sillence MN, Raidal SL, Noble GK (2012) The effect of oral metformin on insulin sensitivity in insulin-resistant ponies. Veterinary Journal 191, 79–84.
| The effect of oral metformin on insulin sensitivity in insulin-resistant ponies.Crossref | GoogleScholarGoogle Scholar |
Turner J, Begum T, Smalligan RD (2016) Canagliflozin-induced diabetic ketoacidosis: case report and review of the literature. Journal of Investigative Medicine High Impact Case Reports 4, 2324709616663231
| Canagliflozin-induced diabetic ketoacidosis: case report and review of the literature.Crossref | GoogleScholarGoogle Scholar | 27635409PubMed |
van Eps AW, Orsini JA (2016) A comparison of seven methods for continuous therapeutic cooling of the equine digit. Equine Veterinary Journal 48, 120–124.
| A comparison of seven methods for continuous therapeutic cooling of the equine digit.Crossref | GoogleScholarGoogle Scholar | 25385194PubMed |
van Eps AW, Walters LJ, Baldwin GI, McGarry M, Pollitt CC (2004) Distal limb cryotherapy for the prevention of acute laminitis. Clinical Techniques in Equine Practice 3, 64–70.
| Distal limb cryotherapy for the prevention of acute laminitis.Crossref | GoogleScholarGoogle Scholar |
Vieitez V, Gomez de Segura IA, Martin-Cuervo M, Gracia LA, Ezquerra LJ (2017) Successful use of lipid emulsion to resuscitate a foal after intravenous lidocaine induced cardiovascular collapse. Equine Veterinary Journal 49, 767–769.
| Successful use of lipid emulsion to resuscitate a foal after intravenous lidocaine induced cardiovascular collapse.Crossref | GoogleScholarGoogle Scholar | 28502090PubMed |
Weiss DJ, Evanson OA, McClenahan D, Fagliari JJ, Dunnwiddie CT, Wells RE (1998) Effect of a competitive inhibitor of platelet aggregation on experimentally induced laminitis in ponies. American Journal of Veterinary Research 59, 814–817.
West E, Bardell D, Morgan R, Senior M (2011) Use of acetaminophen (paracetamol) as a short-term adjunctive analgesic in a laminitic pony. Veterinary Anaesthesia and Analgesia 38, 521–522.
| Use of acetaminophen (paracetamol) as a short-term adjunctive analgesic in a laminitic pony.Crossref | GoogleScholarGoogle Scholar | 21831061PubMed |
Wilcock C, Bailey CJ (1994) Accumulation of metformin by tissues of the normal and diabetic mouse. Xenobiotica 24, 49–57.
| Accumulation of metformin by tissues of the normal and diabetic mouse.Crossref | GoogleScholarGoogle Scholar | 8165821PubMed |
Wilding JP (2014) The role of the kidneys in glucose homeostasis in type 2 diabetes: clinical implications and therapeutic significance through sodium glucose co-transporter 2 inhibitors. Metabolism: Clinical and Experimental 63, 1228–1237.
| The role of the kidneys in glucose homeostasis in type 2 diabetes: clinical implications and therapeutic significance through sodium glucose co-transporter 2 inhibitors.Crossref | GoogleScholarGoogle Scholar |
Wright EM (1998) Genetic disorders of membrane transport: I. Glucose galactose malabsorption. American Journal of Physiology. Gastrointestinal and Liver Physiology 275, G879–G882.
| Genetic disorders of membrane transport: I. Glucose galactose malabsorption.Crossref | GoogleScholarGoogle Scholar |