• 1
    Frank, N., Geor, R.J., Bailey, S.R., Durham, A.E. and Johnson, P.J. (2010) Equine metabolic syndrome. J. Vet. Intern. Med. 24, 467-475.
  • 2
    Carter, R.A., Treiber, K.H., Geor, R.J., Douglass, L. and Harris, P.A. (2009) Prediction of incipient pasture-associated laminitis from hyperinsulinaemia, hyperleptinaemia and generalised and localised obesity in a cohort of ponies. Equine Vet. J. 41, 171-178.
  • 3
    Asplin, K.E., Sillence, M.N., Pollitt, C.C. and McGowan, C.M. (2007) Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies. Vet. J. 174, 530-535.
  • 4
    de Laat, M.A., McGowan, C.M., Sillence, M.N. and Pollitt, C.C. (2010) Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses. Equine Vet. J. 42, 129-135.
  • 5
    Kronfeld, D.S., Hess, T.M., Byrd, B.M. and Splan, R.K. (2005) (abstract) Pre-laminitic metabolic syndrome in genetically predisposed ponies involves compensated insulin resistance. J. Anim. Physiol. Anim. Nutr. (Berl.) 89, 430-431.
  • 6
    Hoffman, R.M., Kronfeld, D.S., Cooper, W.L. and Harris, P.A. (2003) Glucose clearance in grazing mares is affected by diet, pregnancy, and lactation. J. Anim. Sci. 81, 1764-1771.
  • 7
    Suagee, J.K., Corl, B.A., Crisman, M.V., Pleasant, R.S., Thatcher, C.D. and Geor, R.J. (2013) Relationships between body condition score and plasma inflammatory cytokines, insulin, and lipids in a mixed population of light-breed horses. J. Vet. Intern. Med. 27, 157-163.
  • 8
    Treiber, K.H., Kronfeld, D.S., Hess, T.M., Boston, R.C. and Harris, P.A. (2005) Use of proxies and reference quintiles obtained from minimal model analysis for determination of insulin sensitivity and pancreatic beta-cell responsiveness in horses. Am. J. Vet. Res. 66, 2114-2121.
  • 9
    Treiber, K.H., Kronfeld, D.S., Hess, T.M., Byrd, B.M., Splan, R.K. and Staniar, W.B. (2006) Evaluation of genetic and metabolic predispositions and nutritional risk factors for pasture-associated laminitis in ponies. J. Am. Vet. Med. Ass. 228, 1538-1545.
  • 10
    Frank, N., Elliott, S.B., Brandt, L.E. and Keisler, D.H. (2006) Physical characteristics, blood hormone concentrations, and plasma lipid concentrations in obese horses with insulin resistance. J. Am. Vet. Med. Ass. 228, 1383-1390.
  • 11
    Carter, R.A., McCutcheon, L.J., George, L.A., Smith, T.L., Frank, N. and Geor, R.J. (2009) Effects of diet-induced weight gain on insulin sensitivity and plasma hormone and lipid concentrations in horses. Am. J. Vet. Res. 70, 1250-1258.
  • 12
    Carter, R.A., McCutcheon, L.J., Valle, E., Meilahn, E.N. and Geor, R.J. (2010) Effects of exercise training on adiposity, insulin sensitivity, and plasma hormone and lipid concentrations in overweight or obese, insulin-resistant horses. Am. J. Vet. Res. 71, 314-321.
  • 13
    Vick, M.M., Adams, A.A., Murphy, B.A., Sessions, D.R., Horohov, D.W., Cook, R.F., Shelton, B.J. and Fitzgerald, B.P. (2007) Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse. J. Anim. Sci. 85, 1144-1155.
  • 14
    Shanik, M.H., Xu, Y., Skrha, J., Dankner, R., Zick, Y. and Roth, J. (2008) Insulin resistance and hyperinsulinemia: is hyperinsulinemia the cart or the horse? Diabetes Care 31, Suppl. 2, S262-S268.
  • 15
    Mudaliar, S. and Henry, R.R. (2010) Effects of incretin hormones on beta-cell mass and function, body weight, and hepatic and myocardial function. Am. J. Med. 123, S19-S27.
  • 16
    Goutal, C.M., Brugmann, B.L. and Ryan, K.A. (2012) Insulinoma in dogs: a review. J. Am. Anim. Hosp. Ass. 48, 151-163.
  • 17
    Chen, S. (2010) Advanced diagnostic approaches and current medical management of insulinomas and adrenocortical disease in ferrets (Mustela putorius furo). Vet. Clin. North Am. Exot. Anim. Pract. 13, 439-452.
  • 18
    Ross, M.W., Lowe, J.E., Cooper, B.J., Reimers, T.J. and Froscher, B.A. (1983) Hypoglycemic seizures in a Shetland pony. Cornell Vet. 73, 151-169.
  • 19
    Hintz, H.F., Schryver, H.F. and Stevens, C.E. (1978) Digestion and absorption in the hindgut of nonruminant herbivores. J. Anim. Sci. 46, 1803-1807.
  • 20
    Frank, N. (2012) Oral sugar test to diagnose insulin resistance in horses. Proc. Am. Ass Equine Practnrs. 58, 576.
  • 21
    Borer, K.E., Bailey, S.R., Menzies-Gow, N.J., Harris, P.A. and Elliott, J. (2012) Effect of feeding glucose, fructose, and inulin on blood glucose and insulin concentrations in normal ponies and those predisposed to laminitis. J. Anim. Sci. 90, 3003-3011.
  • 22
    Toth, F., Frank, N., Martin-Jimenez, T., Elliott, S.B., Geor, R.J. and Boston, R.C. (2010) Measurement of C-peptide concentrations and responses to somatostatin, glucose infusion, and insulin resistance in horses. Equine Vet. J. 42, 149-155.
  • 23
    Duhlmeier, R., Deegen, E., Fuhrmann, H., Widdel, A. and Sallmann, H.P. (2001) Glucose-dependent insulinotropic polypeptide (GIP) and the enteroinsular axis in equines (Equus caballus). Comp. Biochem. Physiol. A Mol. Integr. Physiol. 129, 563-575.
  • 24
    Chameroy, K., Frank, N., Elliott, S.B. and Schuver, A. (2011) Effects of weight gain on active glucagon-like peptide-1 concentrations in horses with histories of obesity and insulin resistance. J. Vet. Intern. Med. 25, 766 (abstract).
  • 25
    Drucker, D.J. (2003) Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol. Endocrinol. 17, 161-171.
  • 26
    Yamaoka-Tojo, M., Tojo, T., Takahira, N., Matsunaga, A., Aoyama, N., Masuda, T. and Izumi, T. (2010) Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease. Cardiovasc. Diabetol. 9, 17-25.
  • 27
    Ning, J., Hong, T., Yang, X., Mei, S., Liu, Z., Liu, H.Y. and Cao, W. (2011) Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse. Am. J. Physiol. Endocrinol. Metab. 301, E391-E401.
  • 28
    Johnson, P.J. (2002) The equine metabolic syndrome peripheral Cushing's syndrome. Vet. Clin. North Am. Equine Pract. 18, 271-293.
  • 29
    Mehran, A.E., Templeman, N.M., Brigidi, G.S., Lim, G.E., Chu, K.Y., Hu, X., Botezelli, J.D., Asadi, A., Hoffman, B.G., Kieffer, T.J., Bamji, S.X., Clee, S.M. and Johnson, J.D. (2012) Hyperinsulinemia drives diet-induced obesity independently of brain insulin production. Cell Metab. 16, 723-737.
  • 30
    Andreazzi, A.E., Grassiolli, S., Marangon, P.B., Martins, A.G., de Oliveira, J.C., Torrezan, R., Gravena, C., Garcia, R.M. and Mathias, P.C. (2011) Impaired sympathoadrenal axis function contributes to enhanced insulin secretion in prediabetic obese rats. Exp. Diabetes Res. 2011, 947917-947925.
  • 31
    Navas de Solis, C. and Foreman, J.H. (2010) Transient diabetes mellitus in a neonatal Thoroughbred foal. J. Vet. Emerg. Crit. Care 20, 611-615.
  • 32
    Jeffrey, J.R. (1968) Diabetes mellitus secondary to chronic pancreatitis in a pony. J. Am. Vet. Med. Ass. 153, 1168-1175.
  • 33
    Durham, A.E., Hughes, K.J., Cottle, H.J., Rendle, D.I. and Boston, R.C. (2009) Type 2 diabetes mellitus with pancreatic beta cell dysfunction in 3 horses confirmed with minimal model analysis. Equine Vet. J. 41, 924-929.
  • 34
    Staempfli, H.R., Eigenmann, E.J. and Clarke, L.M. (1988) Insulin treatment and development of anti-insulin antibodies in a horse with diabetes mellitus associated with a functional pituitary adenoma. Can. Vet. J. 29, 934-936.
  • 35
    McCoy, D.J. (1986) Diabetes mellitus associated with bilateral granulosa cell tumors in a mare. J. Am. Vet. Med. Ass. 188, 733-735.
  • 36
    Giri, J.K., Magdesian, K.G. and Gaffney, P.M. (2011) Insulin-dependent diabetes mellitus associated with presumed autoimmune polyendocrine syndrome in a mare. Can. Vet. J. 52, 506-512.
  • 37
    Knowles, E.J., Withers, J.M. and Mair, T.S. (2012) Increased plasma fructosamine concentrations in laminitic horses. Equine Vet. J. 44, 226-229.
  • 38
    Waller, A.P., Burns, T.A., Mudge, M.C., Belknap, J.K. and Lacombe, V.A. (2011) Insulin resistance selectively alters cell-surface glucose transporters but not their total protein expression in equine skeletal muscle. J. Vet. Intern. Med. 25, 315-321.
  • 39
    Waller, A.P., Kohler, K., Burns, T.A., Mudge, M.C., Belknap, J.K. and Lacombe, V.A. (2011) Naturally occurring compensated insulin resistance selectively alters glucose transporters in visceral and subcutaneous adipose tissues without change in AS160 activation. Biochim. Biophys. Acta 1812, 1098-1103.
  • 40
    Zhang, H., Dellsperger, K.C. and Zhang, C. (2012) The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: an update. Basic Res. Cardiol. 107, 237-248.
  • 41
    de Laat, M.A., Sillence, M.N., McGowan, C.M. and Pollitt, C.C. (2012) Continuous intravenous infusion of glucose induces endogenous hyperinsulinaemia and lamellar histopathology in Standardbred horses. Vet. J. 191, 317-322.
  • 42
    de Laat, M.A., Kyaw-Tanner, M.T., Sillence, M.N., McGowan, C.M. and Pollitt, C.C. (2012) Advanced glycation endproducts in horses with insulin-induced laminitis. Vet. Immunol. Immunopathol. 145, 395-401.
  • 43
    Shoelson, S.E., Herrero, L. and Naaz, A. (2007) Obesity, inflammation, and insulin resistance. Gastroenterology 132, 2169-2180.
  • 44
    Antuna-Puente, B., Feve, B., Fellahi, S. and Bastard, J.P. (2008) Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab. 34, 2-11.
  • 45
    Carter, R.A., Geor, R.J., Burton Staniar, W., Cubitt, T.A. and Harris, P.A. (2009) Apparent adiposity assessed by standardised scoring systems and morphometric measurements in horses and ponies. Vet. J. 179, 204-210.
  • 46
    Radin, M.J., Sharkey, L.C. and Holycross, B.J. (2009) Adipokines: a review of biological and analytical principles and an update in dogs, cats, and horses. Vet. Clin. Pathol. 38, 136-156.
  • 47
    Goossens, G.H. (2008) The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol. Behav. 94, 206-218.
  • 48
    Trayhurn, P., Wang, B. and Wood, I.S. (2008) Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity? Br. J. Nutr. 100, 227-235.
  • 49
    Serne, E.H., de Jongh, R.T., Eringa, E.C. and Ijzerman , R.G., and Stehouwer, C.D.(2007) Microvascular dysfunction: a potential pathophysiological role in the metabolic syndrome. Hypertension 50, 204-211.
  • 50
    Strissel, K.J., Stancheva, Z., Miyoshi, H., Perfield, J.W., 2nd, DeFuria, J., Jick, Z., Greenberg, A.S. and Obin, M.S. (2007) Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56, 2910-2918.
  • 51
    Cinti, S., Mitchell, G., Barbatelli, G., Murano, I., Ceresi, E., Faloia, E., Wang, S., Fortier, M., Greenberg, A.S. and Obin, M.S. (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J. Lipid Res. 46, 2347-2355.
  • 52
    Murano, I., Barbatelli, G., Parisani, V., Latini, C., Muzzonigro, G., Castellucci, M. and Cinti, S. (2008) Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J. Lipid Res. 49, 1562-1568.
  • 53
    Stienstra, R., Duval, C., Keshtkar, S., van der Laak, J., Kersten, S. and Muller, M. (2008) Peroxisome proliferator-activated receptor gamma activation promotes infiltration of alternatively activated macrophages into adipose tissue. J. Biol. Chem. 283, 22620-22627.
  • 54
    Lumeng, C.N., Bodzin, J.L. and Saltiel, A.R. (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117, 175-184.
  • 55
    Yu, Y.H. and Ginsberg, H.N. (2005) Adipocyte signaling and lipid homeostasis: sequelae of insulin-resistant adipose tissue. Circ. Res. 96, 1042-1052.
  • 56
    Carpentier, A.C. (2008) Postprandial fatty acid metabolism in the development of lipotoxicity and type 2 diabetes. Diabetes Metab. 34, 97-107.
  • 57
    van Herpen, N.A. and Schrauwen-Hinderling, V.B. (2008) Lipid accumulation in non-adipose tissue and lipotoxicity. Physiol. Behav. 94, 231-241.
  • 58
    Kusminski, C.M., Shetty, S., Orci, L., Unger, R.H. and Scherer, P.E. (2009) Diabetes and apoptosis: lipotoxicity. Apoptosis 14, 1484-1495.
  • 59
    Schenk, S., Saberi, M. and Olefsky, J.M. (2008) Insulin sensitivity: modulation by nutrients and inflammation. J. Clin. Invest. 118, 2992-3002.
  • 60
    Martin, M.U. and Wesche, H. (2002) Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family. Biochim. Biophys. Acta 1592, 265-280.
  • 61
    Hotamisligil, G.S. (2006) Inflammation and metabolic disorders. Nature 444, 860-867.
  • 62
    Muniyappa, R., Iantorno, M. and Quon, M.J. (2008) An integrated view of insulin resistance and endothelial dysfunction. Endocrinol. Metab. Clin. North Am. 37, 685-711; ix-x.
  • 63
    Kim, J.A., Montagnani, M., Koh, K.K. and Quon, M.J. (2006) Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 113, 1888-1904.
  • 64
    Fantuzzi, G. (2005) Adipose tissue, adipokines, and inflammation. J. Allergy Clin. Immunol. 115, 911-919; quiz 920.
  • 65
    Suagee, J.K., Corl, B.A., Crisman, M.V., Hulver, M.W., McCutcheon, L.J. and Geor, R.J. (2011) Effects of acute hyperinsulinemia on inflammatory proteins in horses. Vet. Immunol. Immunopathol. 142, 141-146.
  • 66
    Holbrook, T.C., Tipton, T. and McFarlane, D. (2012) Neutrophil and cytokine dysregulation in hyperinsulinemic obese horses. Vet. Immunol. Immunopathol. 145, 283-289.
  • 67
    Burns, T.A., Geor, R.J., Mudge, M.C., McCutcheon, L.J., Hinchcliff, K.W. and Belknap, J.K. (2010) Proinflammatory cytokine and chemokine gene expression profiles in subcutaneous and visceral adipose tissue depots of insulin-resistant and insulin-sensitive light breed horses. J. Vet. Intern. Med. 24, 932-939.
  • 68
    Tarantino, G., Saldalamacchia, G., Conca, P. and Arena, A. (2007) Non-alcoholic fatty liver disease: further expression of the metabolic syndrome. J. Gastroenterol. Hepatol. 22, 293-303.
  • 69
    Tarantino, G., Savastano, S. and Colao, A. (2010) Hepatic steatosis, low-grade chronic inflammation and hormone/growth factor/adipokine imbalance. World J. Gastroenterol. 16, 4773-4783.
  • 70
    Perlemuter, G., Bigorgne, A., Cassard-Doulcier, A.M. and Naveau, S. (2007) Nonalcoholic fatty liver disease: from pathogenesis to patient care. Nat. Clin. Pract. Endocrinol. Metab. 3, 458-469.
  • 71
    Postic, C. and Girard, J. (2008) Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J. Clin. Invest. 118, 829-838.
  • 72
    Neuschwander-Tetri, B.A. (2010) Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites. Hepatology 52, 774-788.
  • 73
    Cai, D., Yuan, M., Frantz, D.F., Melendez, P.A., Hansen, L., Lee, J. and Shoelson, S.E. (2005) Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat. Med. 11, 183-190.
  • 74
    Item, F. and Konrad, D. (2012) Visceral fat and metabolic inflammation: the portal theory revisited. Obes. Rev. 13, Suppl. 2, 30-39.
  • 75
    Sparks, J.D., Sparks, C.E. and Adeli, K. (2012) Selective hepatic insulin resistance, VLDL overproduction, and hypertriglyceridemia. Arterioscler. Thromb. Vasc. Biol. 32, 2104-2112.
  • 76
    Valenti, L., Dongiovanni, P. and Fargion, S. (2012) Diagnostic and therapeutic implications of the association between ferritin level and severity of nonalcoholic fatty liver disease. World J. Gastroenterol. 18, 3782-3786.
  • 77
    Nielsen, B.D., Vick, M.M. and Dennis, P.M. (2012) A potential link between insulin resistance and iron overload disorder in browsing rhinoceroses investigated through the use of an equine model. J. Zoo Wildl. Med. 43, S61-S65.
  • 78
    Buff, P.R., Dodds, A.C., Morrison, C.D., Whitley, N.C., McFadin, E.L., Daniel, J.A., Djiane, J. and Keisler, D.H. (2002) Leptin in horses: tissue localization and relationship between peripheral concentrations of leptin and body condition. J. Anim. Sci. 80, 2942-2948.
  • 79
    Gentry, L.R., Thompson, D.L., Jr, Gentry, G.T., Jr, Davis, K.A., Godke, R.A. and Cartmill, J.A. (2002) The relationship between body condition, leptin, and reproductive and hormonal characteristics of mares during the seasonal anovulatory period. J. Anim. Sci. 80, 2695-2703.
  • 80
    Kearns, C.F., McKeever, K.H., Roegner, V., Brady, S.M. and Malinowski, K. (2006) Adiponectin and leptin are related to fat mass in horses. Vet. J. 172, 460-465.
  • 81
    Meier, U. and Gressner, A.M. (2004) Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin. Chem. 50, 1511-1525.
  • 82
    Porte, D., Jr, Baskin, D.G. and Schwartz, M.W. (2002) Leptin and insulin action in the central nervous system. Nutr. Rev. 60, S20-S29; discussion S68-84, 85-27.
  • 83
    Cohen, P., Miyazaki, M., Socci, N.D., Hagge-Greenberg, A., Liedtke, W., Soukas, A.A., Sharma, R., Hudgins, L.C., Ntambi, J.M. and Friedman, J.M. (2002) Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science 297, 240-243.
  • 84
    Pandit, R., de Jong, J.W., Vanderschuren, L.J. and Adan, R.A. (2011) Neurobiology of overeating and obesity: the role of melanocortins and beyond. Eur. J. Pharmacol. 660, 28-42.
  • 85
    Diez, E., Lopez, I., Perez, C., Pineda, C. and Aguilera-Tejero, E. (2012) Plasma leptin concentration in donkeys. Vet. Q. 32, 13-16.
  • 86
    Caltabilota, T.J., Earl, L.R., Thompson, D.L., Jr, Clavier, S.E. and Mitcham, P.B. (2010) Hyperleptinemia in mares and geldings: assessment of insulin sensitivity from glucose responses to insulin injection. J. Anim. Sci. 88, 2940-2949.
  • 87
    Shehzad, A., Iqbal, W., Shehzad, O. and Lee, Y.S. (2012) Adiponectin: regulation of its production and its role in human diseases. Hormones (Athens) 11, 8-20.
  • 88
    Maeda, N., Shimomura, I., Kishida, K., Nishizawa, H., Matsuda, M., Nagaretani, H., Furuyama, N., Kondo, H., Takahashi, M., Arita, Y., Komuro, R., Ouchi, N., Kihara, S., Tochino, Y., Okutomi, K., Horie, M., Takeda, S., Aoyama, T., Funahashi, T. and Matsuzawa, Y. (2002) Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat. Med. 8, 731-737.
  • 89
    Schraw, T., Wang, Z.V., Halberg, N., Hawkins, M. and Scherer, P.E. (2008) Plasma adiponectin complexes have distinct biochemical characteristics. Endocrinology 149, 2270-2282.
  • 90
    Wooldridge, A.A., Edwards, H.G., Plaisance, E.P., Applegate, R., Taylor, D.R., Taintor, J., Zhong, Q. and Judd, R.L. (2012) Evaluation of high-molecular weight adiponectin in horses. Am. J. Vet. Res. 73, 1230-1240.
  • 91
    Goldstein, B.J. and Scalia, R. (2004) Adiponectin: a novel adipokine linking adipocytes and vascular function. J. Clin. Endocrinol. Metab. 89, 2563-2568.
  • 92
    Knight, S.F. and Imig, J.D. (2007) Obesity, insulin resistance, and renal function. Microcirculation 14, 349-362.
  • 93
    Sharma, V. and McNeill, J.H. (2005) The emerging roles of leptin and ghrelin in cardiovascular physiology and pathophysiology. Curr. Vasc. Pharmacol. 3, 169-180.
  • 94
    Teoh, H., Quan, A., Bang, K.W., Wang, G., Lovren, F., Vu, V., Haitsma, J.J., Szmitko, P.E., Al-Omran, M., Wang, C.H., Gupta, M., Peterson, M.D., Zhang, H., Chan, L., Freedman, J., Sweeney, G. and Verma, S. (2008) Adiponectin deficiency promotes endothelial activation and profoundly exacerbates sepsis-related mortality. Am. J. Physiol. Endocrinol. Metab. 295, E658-E664.
  • 95
    Ouchi, N., Ohishi, M., Kihara, S., Funahashi, T., Nakamura, T., Nagaretani, H., Kumada, M., Ohashi, K., Okamoto, Y., Nishizawa, H., Kishida, K., Maeda, N., Nagasawa, A., Kobayashi, H., Hiraoka, H., Komai, N., Kaibe, M., Rakugi, H., Ogihara, T. and Matsuzawa, Y. (2003) Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension 42, 231-234.
  • 96
    Ouedraogo, R., Gong, Y., Berzins, B., Wu, X., Mahadev, K., Hough, K., Chan, L., Goldstein, B.J. and Scalia, R. (2007) Adiponectin deficiency increases leukocyte-endothelium interactions via upregulation of endothelial cell adhesion molecules in vivo. J. Clin. Invest. 117, 1718-1726.
  • 97
    Tilg, H. and Wolf, A.M. (2005) Adiponectin: a key fat-derived molecule regulating inflammation. Expert Opin. Ther. Targets 9, 245-251.
  • 98
    Korda, M., Kubant, R., Patton, S. and Malinski, T. (2008) Leptin-induced endothelial dysfunction in obesity. Am. J. Physiol. Heart Circ. Physiol. 295, H1514-H1521.
  • 99
    Singhal, A. (2005) Endothelial dysfunction: role in obesity-related disorders and the early origins of CVD. Proc. Nutr. Soc. 64, 15-22.
  • 100
    McGowan, T.W., Pinchbeck, G.P. and McGowan, C.M. (2013) Prevalence, risk factors and clinical signs predictive for equine pituitary pars intermedia dysfunction in aged horses. Equine Vet. J. 45, 74-79.
  • 101
    Rafacho, A., Marroqui, L., Taboga, S.R., Abrantes, J.L., Silveira, L.R., Boschero, A.C., Carneiro, E.M., Bosqueiro, J.R., Nadal, A. and Quesada, I. (2010) Glucocorticoids in vivo induce both insulin hypersecretion and enhanced glucose sensitivity of stimulus-secretion coupling in isolated rat islets. Endocrinology 151, 85-95.
  • 102
    Tiley, H.A., Geor, R.J. and McCutcheon, L.J. (2007) Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses. Am. J. Vet. Res. 68, 753-759.
  • 103
    Toth, F., Frank, N., Geor, R.J. and Boston, R.C. (2010) Effects of pretreatment with dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics in horses. Am. J. Vet. Res. 71, 60-68.
  • 104
    Peterson, M.E., Altszuler, N. and Nichols, C.E. (1984) Decreased insulin sensitivity and glucose tolerance in spontaneous canine hyperadrenocorticism. Res. Vet. Sci. 36, 177-182.
  • 105
    Montgomery, T.M., Nelson, R.W., Feldman, E.C., Robertson, K. and Polonsky, K.S. (1996) Basal and glucagon-stimulated plasma C-peptide concentrations in healthy dogs, dogs with diabetes mellitus, and dogs with hyperadrenocorticism. J. Vet. Intern. Med. 10, 116-122.
  • 106
    Orth, D.N., Holscher, M.A., Wilson, M.G., Nicholson, W.E., Plue, R.E. and Mount, C.D. (1982) Equine Cushing's disease: plasma immunoreactive proopiolipomelanocortin peptide and cortisol levels basally and in response to diagnostic tests. Endocrinology 110, 1430-1441.
  • 107
    Wilson, M.G., Nicholson, W.E., Holscher, M.A., Sherrell, B.J., Mount, C.D. and Orth, D.N. (1982) Proopiolipomelanocortin peptides in normal pituitary, pituitary tumor, and plasma of normal and Cushing's horses. Endocrinology 110, 941-954.
  • 108
    Marshall, J.B., Kapcala, L.P., Manning, L.D. and McCullough, A.J. (1984) Effect of corticotropin-like intermediate lobe peptide on pancreatic exocrine function in isolated rat pancreatic lobules. J. Clin. Invest. 74, 1886-1889.
  • 109
    McFarlane, D., Beech, J. and Cribb, A. (2006) Alpha-melanocyte stimulating hormone release in response to thyrotropin releasing hormone in healthy horses, horses with pituitary pars intermedia dysfunction and equine pars intermedia explants. Domest. Anim. Endocrinol. 30, 276-288.
  • 110
    Obici, S., Feng, Z., Tan, J., Liu, L., Karkanias, G. and Rossetti, L. (2001) Central melanocortin receptors regulate insulin action. J. Clin. Invest. 108, 1079-1085.
  • 111
    Schott, H.C., 2nd (2002) Pituitary pars intermedia dysfunction: equine Cushing's disease. Vet. Clin. North Am.: Equine Pract. 18, 237-270.
  • 112
    McFarlane, D. (2011) Equine pituitary pars intermedia dysfunction. Vet. Clin. North Am.: Equine Pract. 27, 93-113.
  • 113
    van der Kolk, J.H., Wensing, T., Kalsbeek, H.C. and Breukink, H.J. (1995) Laboratory diagnosis of equine pituitary pars intermedia adenoma. Domest. Anim. Endocrinol. 12, 35-39.
  • 114
    Reeves, H.J., Lees, R. and McGowan, C.M. (2001) Measurement of basal serum insulin concentration in the diagnosis of Cushing's disease in ponies. Vet. Rec. 149, 449-452.
  • 115
    McGowan, C.M., Frost, R., Pfeiffer, D.U. and Neiger, R. (2004) Serum insulin concentrations in horses with equine Cushing's syndrome: response to a cortisol inhibitor and prognostic value. Equine Vet. J. 36, 295-298.
  • 116
    Marik, P.E. and Raghavan, M. (2004) Stress-hyperglycemia, insulin and immunomodulation in sepsis. Intens. Care Med. 30, 748-756.
  • 117
    McCowen, K.C., Malhotra, A. and Bistrian, B.R. (2001) Stress-induced hyperglycemia. Crit. Care Clin. 17, 107-124.
  • 118
    Knieriem, M., Otto, C.M. and Macintire, D. (2007) Hyperglycemia in critically ill patients. Compend. Contin. Educ. Vet. 29, 360-362; 364-372; quiz 372.
  • 119
    Toth, F., Frank, N., Elliott, S.B., Geor, R.J. and Boston, R.C. (2008) Effects of an intravenous endotoxin challenge on glucose and insulin dynamics in horses. Am. J. Vet. Res. 69, 82-88.
  • 120
    Tadros, E.M. and Frank, N. (2012) Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses. Am. J. Vet. Res. 73, 1394-1402.
  • 121
    Tanti, J.F. and Jager, J. (2009) Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation. Curr. Opin. Pharmacol. 9, 753-762.
  • 122
    Buren, J., Liu, H.X., Jensen, J. and Eriksson, J.W. (2002) Dexamethasone impairs insulin signalling and glucose transport by depletion of insulin receptor substrate-1, phosphatidylinositol 3-kinase and protein kinase B in primary cultured rat adipocytes. Eur. J. Endocrinol. 146, 419-429.
  • 123
    Lundgren, M., Buren, J., Ruge, T., Myrnas, T. and Eriksson, J.W. (2004) Glucocorticoids down-regulate glucose uptake capacity and insulin-signaling proteins in omental but not subcutaneous human adipocytes. J. Clin. Endocrinol. Metab. 89, 2989-2997.
  • 124
    Singleton, J.R., Baker, B.L. and Thorburn, A. (2000) Dexamethasone inhibits insulin-like growth factor signaling and potentiates myoblast apoptosis. Endocrinology 141, 2945-2950.
  • 125
    Sakoda, H., Ogihara, T., Anai, M., Funaki, M., Inukai, K., Katagiri, H., Fukushima, Y., Onishi, Y., Ono, H., Fujishiro, M., Kikuchi, M., Oka, Y. and Asano, T. (2000) Dexamethasone-induced insulin resistance in 3T3-L1 adipocytes is due to inhibition of glucose transport rather than insulin signal transduction. Diabetes 49, 1700-1708.
  • 126
    Mizock, B.A. (1995) Alterations in carbohydrate metabolism during stress: a review of the literature. Am. J. Med. 98, 75-84.
  • 127
    Mizock, B.A. (2001) Alterations in fuel metabolism in critical illness: hyperglycaemia. Best Pract. Res. Clin. Endocrinol. Metab. 15, 533-551.
  • 128
    Waitt, L.H. and Cebra, C.K. (2009) Characterization of hypertriglyceridemia and response to treatment with insulin in horses, ponies, and donkeys: 44 cases (1995–2005). J. Am. Vet. Med. Ass. 234, 915-919.
  • 129
    van der Kolk, J.H., Wensing, T., Kalsbeek, H.C. and Breukink, H.J. (1995) Lipid metabolism in horses with hyperadrenocorticism. J. Am. Vet. Med. Ass. 206, 1010-1012.
  • 130
    Freestone, J.F., Wolfsheimer, K.J., Ford, R.B., Church, G. and Bessin, R. (1991) Triglyceride, insulin, and cortisol responses of ponies to fasting and dexamethasone administration. J. Vet. Intern. Med. 5, 15-22.
  • 131
    Cebra, C.K. and Tornquist, S.J. (2004) Assessment of the effects of epinephrine and insulin on plasma and serum biochemical variables in llamas and alpacas. Am. J. Vet. Res. 65, 1692-1696.
  • 132
    Khomulo, P.S. and Gritskevich, N.L. (1984) [Physiologico-biochemical correlates of the behavioral reactions in cats under states of emotional stress]. Vopr. Med. Khim. 30, 53-55.
  • 133
    Fowden, A.L., Forhead, A.J. and Ousey, J.C. (2012) Endocrine adaptations in the foal over the perinatal period. Equine Vet. J. 44, Suppl. 41, 130-139.
  • 134
    Holdstock, N.B., Allen, V.L., Bloomfield, M.R., Hales, C.N. and Fowden, A.L. (2004) Development of insulin and proinsulin secretion in newborn pony foals. J. Endocrinol. 181, 469-476.
  • 135
    Fowden, A.L., Silver, M., Ellis, L., Ousey, J. and Rossdale, P.D. (1984) Studies on equine prematurity 3: insulin secretion in the foal during the perinatal period. Equine Vet. J. 16, 286-291.
  • 136
    Fowden, A.L., Ellis, L. and Rossdale, P.D. (1982) Pancreatic beta cell function in the neonatal foal. J. Reprod. Fertil. Suppl. 32, 529-535.
  • 137
    Lester, G.D. (2005) Maturity of the neonatal foal. Vet. Clin. North Am.: Equine Pract. 21, 333-355.
  • 138
    Hurcombe, S.D., Toribio, R.E., Slovis, N., Kohn, C.W., Refsal, K., Saville, W. and Mudge, M.C. (2008) Blood arginine vasopressin, adrenocorticotropin hormone, and cortisol concentrations at admission in septic and critically ill foals and their association with survival. J. Vet. Intern. Med. 22, 639-647.
  • 139
    Gold, J.R., Divers, T.J., Barton, M.H., Lamb, S.V., Place, N.J., Mohammed, H.O. and Bain, F.T. (2007) Plasma adrenocorticotropin, cortisol, and adrenocorticotropin/cortisol ratios in septic and normal-term foals. J. Vet. Intern. Med. 21, 791-796.
  • 140
    Hart, K.A., Slovis, N.M. and Barton, M.H. (2009) Hypothalamic-pituitary-adrenal axis dysfunction in hospitalized neonatal foals. J. Vet. Intern. Med. 23, 901-912.
  • 141
    Hollis, A.R., Furr, M.O., Magdesian, K.G., Axon, J.E., Ludlow, V., Boston, R.C. and Corley, K.T. (2008) Blood glucose concentrations in critically ill neonatal foals. J. Vet. Intern. Med. 22, 1223-1227.
  • 142
    Barsnick, R.J., Hurcombe, S.D., Smith, P.A., Slovis, N.M., Sprayberry, K.A., Saville, W.J. and Toribio, R.E. (2011) Insulin, glucagon, and leptin in critically ill foals. J. Vet. Intern. Med. 25, 123-131.
  • 143
    Mitanchez, D. (2007) Glucose regulation in preterm newborn infants. Horm. Res. 68, 265-271.
  • 144
    Beardsall, K., Diderholm, B.M. and Dunger, D.B. (2008) Insulin and carbohydrate metabolism. Best Pract. Res. Clin. Endocrinol. Metab. 22, 41-55.
  • 145
    Mitanchez-Mokhtari, D., Lahlou, N., Kieffer, F., Magny, J.F., Roger, M. and Voyer, M. (2004) Both relative insulin resistance and defective islet beta-cell processing of proinsulin are responsible for transient hyperglycemia in extremely preterm infants. Pediatrics 113, 537-541.
  • 146
    Decaro, M.H. and Vain, N.E. (2011) Hyperglycaemia in preterm neonates: what to know, what to do. Early Hum. Dev. 87, Suppl. 1, S19-S22.
  • 147
    Holdstock, N.B., Allen, V.L. and Fowden, A.L. (2012) Pancreatic endocrine function in newborn pony foals after induced or spontaneous delivery at term. Equine Vet. J. 44, Suppl. 41, 30-37.
  • 148
    Wang, X., Cui, Y., Tong, X., Ye, H. and Li, S. (2007) Glucose and lipid metabolism in small-for-gestational-age infants at 72 hours of age. J. Clin. Endocrinol. Metab. 92, 681-684.
  • 149
    Bazaes, R.A., Salazar, T.E., Pittaluga, E., Pena, V., Alegria, A., Iniguez, G., Ong, K.K., Dunger, D.B. and Mericq, M.V. (2003) Glucose and lipid metabolism in small for gestational age infants at 48 hours of age. Pediatrics 111, 804-809.
  • 150
    Hays, S.P., Smith, E.O. and Sunehag, A.L. (2006) Hyperglycemia is a risk factor for early death and morbidity in extremely low birth-weight infants. Pediatrics 118, 1811-1818.
  • 151
    Kao, L.S., Morris, B.H., Lally, K.P., Stewart, C.D., Huseby, V. and Kennedy, K.A. (2006) Hyperglycemia and morbidity and mortality in extremely low birth weight infants. J. Perinatol. 26, 730-736.
  • 152
    Cohen, N.D. (1994) Causes of and farm management factors associated with disease and death in foals. J. Am. Vet. Med. Ass. 204, 1644-1651.
  • 153
    Marsh, P.S. and Palmer, J.E. (2001) Bacterial isolates from blood and their susceptibility patterns in critically ill foals: 543 cases (1991–1998). J. Am. Vet. Med. Ass. 218, 1608-1610.
  • 154
    Corley, K.T., Donaldson, L.L. and Furr, M.O. (2005) Arterial lactate concentration, hospital survival, sepsis and SIRS in critically ill neonatal foals. Equine Vet. J. 37, 53-59.
  • 155
    Russell, C.M., Axon, J.E., Blishen, A. and Begg, A.P. (2008) Blood culture isolates and antimicrobial sensitivities from 427 critically ill neonatal foals. Aust. Vet. J. 86, 266-271.
  • 156
    Hollis, A.R., Wilkins, P.A., Palmer, J.E. and Boston, R.C. (2008) Bacteremia in equine neonatal diarrhea: a retrospective study (1990–2007). J. Vet. Intern. Med. 22, 1203-1209.
  • 157
    Barsnick, R.J. and Toribio, R.E. (2011) Endocrinology of the equine neonate energy metabolism in health and critical illness. Vet. Clin. North Am.: Equine Pract. 27, 49-58.
  • 158
    Butte, N.F. (2000) Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am. J. Clin. Nutr. 71, 1256S-1261S.
  • 159
    Fowden, A.L., Comline, R.S. and Silver, M. (1984) Insulin secretion and carbohydrate metabolism during pregnancy in the mare. Equine Vet. J. 16, 239-246.
  • 160
    George, L.A., Staniar, W.B., Cubitt, T.A., Treiber, K.H., Harris, P.A. and Geor, R.J. (2011) Evaluation of the effects of pregnancy on insulin sensitivity, insulin secretion, and glucose dynamics in Thoroughbred mares. Am. J. Vet. Res. 72, 666-674.
  • 161
    Firshman, A.M. and Valberg, S.J. (2007) Factors affecting clinical assessment of insulin sensitivity in horses. Equine Vet. J. 39, 567-575.
  • 162
    Bertin, F.R. and Sojka-Kritchevsky, J.E. (2013) Comparison of a 2-step insulin-response test to conventional insulin-sensitivity testing in horses. Domest. Anim. Endocrinol. 44, 19-25.
  • 163
    Eiler, H., Frank, N., Andrews, F.M., Oliver, J.W. and Fecteau, K.A. (2005) Physiologic assessment of blood glucose homeostasis via combined intravenous glucose and insulin testing in horses. Am. J. Vet. Res. 66, 1598-1604.
  • 164
    Dugdale, A.H., Curtis, G.C., Cripps, P., Harris, P.A. and Argo, C.M. (2010) Effect of dietary restriction on body condition, composition and welfare of overweight and obese pony mares. Equine Vet. J. 42, 600-610.
  • 165
    Argo, C.M., Curtis, G.C., Grove-White, D., Dugdale, A.H., Barfoot, C.F. and Harris, P.A. (2012) Weight loss resistance: a further consideration for the nutritional management of obese Equidae. Vet. J. 194, 179-188.
  • 166
    Longland, A.C., Barfoot, C. and Harris, P.A. (2011) Effects of soaking on the water-soluble carbohydrate and crude protein content of hay. Vet. Rec. 168, 618-623.
  • 167
    Klinkhamer, K., Menheere, P.P. and van der Kolk, J.H. (2011) Basal glucose metabolism and peripheral insulin sensitivity in equine pituitary pars intermedia dysfunction. Vet. Q. 31, 19-28.
  • 168
    Frank, N., Elliott, S.B. and Boston, R.C. (2008) Effects of long-term oral administration of levothyroxine sodium on glucose dynamics in healthy adult horses. Am. J. Vet. Res. 69, 76-81.
  • 169
    Durham, A.E., Rendle, D.I. and Newton, J.E. (2008) The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance. Equine Vet. J. 40, 493-500.
  • 170
    Tinworth, K.D., Boston, R.C., Harris, P.A., Sillence, M.N., Raidal, S.L. and Noble, G.K. (2012) The effect of oral metformin on insulin sensitivity in insulin-resistant ponies. Vet. J. 191, 79-84.
  • 171
    Hustace, J.L., Firshman, A.M. and Mata, J.E. (2009) Pharmacokinetics and bioavailability of metformin in horses. Am. J. Vet. Res. 70, 665-668.
  • 172
    Rendle, D.I., Rutledge, F., Hughes, K.J., Heller, J. and Durham, A.E. (2013) Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses. Equine Vet. J. 45, 751-754.