Abstract
Depletion of pancreatic acinar cell polyamines in response to activation of polyamine catabolism is associated with the development of acute pancreatitis in experimental rodent models. The disease is characterized by general hallmarks seen also in human pancreatitis, such as accumulation of intraperitoneal ascites, acinar cell necrosis, and pancreatic as well as remote organ edema and inflammation. Thus, these animals make useful models for the human disease. Determination of these hallmarks can be used to assess the severity of the disease and to evaluate the efficacy of any therapy applied. The metabolic changes seen in genetically modified mice with either accelerated or inactivated polyamine catabolism have revealed that polyamine catabolism is involved in the regulation of glucose and lipid metabolism. The simplest method to determine the metabolic phenotype of the animal is to assess the concentrations of blood metabolites. Fasting blood glucose level is an indicator of overall glucose homeostasis, whereas fasting insulin level is a useful marker of insulin sensitivity. A more detailed analysis of glucose homeostasis and insulin sensitivity can be obtained by intraperitoneal glucose and insulin tolerance tests. Blood lipid levels mainly reflect triglyceride, free fatty acid, and cholesterol metabolism. Altered blood glucose and/or lipid levels are associated with several diseases, e.g., diabetes, Cushing’s syndrome, hyperthyroidism, atherosclerosis, pancreatitis, and dysfunction of the liver and kidneys.
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Alhonen L, Parkkinen JJ, Keinänen T, Sinervirta R, Herzig KH, Jänne J (2000) Activation of polyamine catabolism in transgenic rats induces acute pancreatitis. Proc Natl Acad Sci U S A 97:8290–8295
Hyvönen MT, Herzig KH, Sinervirta R, Albrecht E, Nordback I, Sand J, Keinänen TA, Vepsäläinen J, Grigorenko N, Khomutov AR, Krüger B, Jänne J, Alhonen L (2006) Activated polyamine catabolism in acute pancreatitis: alpha-methylated polyamine analogues prevent trypsinogen activation and pancreatitis-associated mortality. Am J Pathol 168:115–122
Pirinen E, Kuulasmaa T, Pietilä M, Heikkinen S, Tusa M, Itkonen P, Boman S, Skommer J, Virkamäki A, Hohtola E, Kettunen M, Fatrai S, Kansanen E, Koota S, Niiranen K, Parkkinen J, Levonen AL, Ylä-Herttuala S, Hiltunen JK, Alhonen L, Smith U, Jänne J, Laakso M (2007) Enhanced polyamine catabolism alters homeostatic control of white adipose tissue mass, energy expenditure, and glucose metabolism. Mol Cell Biol 27:4953–4967
Pirinen E, Gylling H, Itkonen P, Yaluri N, Heikkinen S, Pietilä M, Kuulasmaa T, Tusa M, Cerrada-Gimenez M, Pihlajamäki J, Alhonen L, Jänne J, Miettinen T, Laakso M (2010) Activated polyamine catabolism leads to low cholesterol levels by enhancing bile acid synthesis. Amino Acids 38:549–560
Niiranen K, Keinänen TA, Pirinen E, Heikkinen S, Tusa M, Fatrai S, Suppola S, Pietilä M, Uimari A, Laakso M, Alhonen L, Jänne J (2006) Mice with targeted disruption of spermidine/spermine N1-acetyltransferase gene maintain nearly normal tissue polyamine homeostasis but show signs of insulin resistance upon aging. J Cell Mol Med 10:933–945
Tani S, Itoh H, Okabayashi Y, Nakamura T, Fujii M, Fujisawa T, Koide M, Otsuki M (1990) New model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats. Dig Dis Sci 35:367–374
Niederau C, Niederau M, Luthen R, Strohmeyer G, Ferrell LD, Grendell JH (1990) Pancreatic exocrine secretion in acute experimental pancreatitis. Gastroenterology 99:1120–1127
Lankisch PG, Ihse I (1987) Bile-induced acute experimental pancreatitis. Scand J Gastroenterol 22:257–260
Lombardi B, Estes LW, Longnecker DS (1975) Acute hemorrhagic pancreatitis (massive necrosis) with fat necrosis induced in mice by DL-ethionine fed with a choline-deficient diet. Am J Pathol 79:465–480
Rakonczay Z Jr, Hegyi P, Dosa S, Ivanyi B, Jarmay K, Biczo G, Hracsko Z, Varga IS, Karg E, Kaszaki J, Varro A, Lonovics J, Boros I, Gukovsky I, Gukovskaya AS, Pandol SJ, Takacs T (2008) A new severe acute necrotizing pancreatitis model induced by L-ornithine in rats. Crit Care Med 36:2117–2127
Aronoff S, Berkowitz K, Shreiner B, Want L (2004) Glucose metabolism and regulation: beyond insulin and glucagon. Diabetes Spectr 17:183–190
Murray RK, Granner DK, Mayes PA, Rodwell VW (1993) Harper’s biochemistry, 23rd edn. Prentice-Hall, Englewood Cliffs
DeFronzo RA (2004) Pathogenesis of type 2 diabetes mellitus. Med Clin North Am 88:787–835, ix
Taskinen MR (2003) Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 46:733–749
Argmann, CA, Houten SM, Champy MF, Auwerx J (2006) Lipid and bile acid analysis. Curr Protoc Mol Biol Chapter 29:Unit 29B
Heikkinen S, Argmann CA, Champy MF, Auwerx J (2007) Evaluation of glucose homeostasis. Curr Protoc Mol Biol Chapter 29:Unit 29B
Acknowledgements
The authors thank Riitta Sinervirta and Sisko Juutinen for technical assistance and Taina Roiha for the photography of material for Fig. 1. This work was supported by the Academy of Finland.
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Uimari, A., Hyvönen, M.T., Pirinen, E., Alhonen, L. (2011). Transgenic Rodents with Altered SSAT Expression as Models of Pancreatitis and Altered Glucose and Lipid Metabolism. In: Pegg, A., Casero, Jr., R. (eds) Polyamines. Methods in Molecular Biology, vol 720. Humana Press. https://doi.org/10.1007/978-1-61779-034-8_8
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DOI: https://doi.org/10.1007/978-1-61779-034-8_8
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