Optimization of animal model for investigation of pathogenesis of type 2 diabetes
Rushchak VV, Kovalenko VM, Voronina AK, Kitam VO, Maksymchuk OV, Chashchyn MO.
- Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine
- Institute of Pharmacology and Toxicology, Academy ofMedical Sciences of Ukraine, Kyiv, Ukraine
Diabetes mellitus is one of the three most common modern diseases. A number of animal models is used in investigations of the mechanisms of development of the disease. Most of these models replicate the symptoms of type 1 diabetes mellitus. The development of type 2 diabetes is caused by the insulin resistance, hyperglycemia, structural and functional disorders of the pancreatic cells. Investigation of pathogenesis of type 2 diabetes is complicated by the lack of adequate models of this disease. In this work, based on existing hyperglycemia model, we propose the model of metabolic syndrome as a precursor of type 2 diabetes. The development of metabolic syndrome symptoms was caused by 28 days long intramuscular injection of protamine sulfate to guinea pigs at a dose of 15 mg/kg along with keeping of animals on a high glucose diet. Increased blood glucose and cholesterol levels, reduction of glycogen in liver, the structural and functional damage and reduce in the number of functionally active ?-cells in the pancreas of the experimental animals were observed. The results confrm the development of the metabolic syndrome symptoms in experimental animals, which makes it possible to use such methodical approach in creation of promising type 2 diabetes model.
metabolic syndrome, diabetes, protamine sulfate,animal model, guinea pigs.
- Babak OJ, Kolesnikova EV, Kravchenko NA Liver fibrosis: current concepts of mechanisms, methods of diagnostics and treatment . Such. gastroenterologiya. 2009. N 2. P. 5-17.
- Bodnar PM, Kononenko LO, Mikhalchishin GP Metabolic syndrome (literature review) . Zhurn. AMN Ukraini.- 2000. N 4. P. 34-37.
- Buhtiarova T., Stefanov O., Kovalenko V. Medicines. Good laboratory practice . Order of the Ministry of Health of Ukraine N 95 of 16.02.2009 27 p.
- Zanozina OV, Borovkov NN, Balabolkin MI. The necessity and sufficiency of the use of anti-oxidants in the treatment of patients with type 2 diabetes . Bul. experiment. biology and medicine. 2006. Approx. 1. P. 112-118.
- Korzhevsky DE, Gilyarov AV Fundamentals of histological technique M .: SpecLit, 2010. 94 p.
- Kuzishin OV, Kovalyshin NV, Almashina HV Diabetes mellitus: 1. Theoretical part (review) . Med. chemistry. 2010. N 2. P. 74-115.
- Mikhailov VV Fundamentals of pathological physiology: a guide for doctors M .: Medicine, 2001. 704 p.
- Podilchak MD, Vdovichenko VI, Terletskaya LM Lipid peroxidation and serum peroxidase activity in diseases of the hepatobiliary system . Lik. case. 1996. N 1. P. 110-112.
- Runihin A.Yu., Novikova Yu.V. Modern aspects of pathogenesis and treatment of type 2 diabetes . Endocrinology. 2007. 15, N 27. P.58-70.
- Ulyanov A.M., Tarasov Yu.A. Insular system of animals in chronic heparin deficiency . Questions med. chemistry. 2000. 46, No. 2. P. 149-154.
- Chasova TE Basic principles of treatment of type 1 diabetes . Rus. Med . 2003. 11, N 27. P. 15-20.
- Ahn T.,Yun, C.H., Oh D.B., Tissue-specifc effect of ascorbic acid supplementation on the expression of cytochrome P450 2E1 and oxidative stress in streptozotocin-induced diabetic rats . Toxicol. Lett. 2006. N 166. R. 27-36.
- Dean-Roger T., Fu Schanlin, Stroker R.D.M. Vios-hemistru and rathologu of gadisal-mediated rgotein ohidation . Vioshem. J. 1997. 324, N 1. R. 1-18.
- Folli F, Corradi D. The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro- and mac-rovascular complications: avenues for a mechanistic-based therapeutic approach . Curr. Diabetes Rev. 2011. 7, N 5. R. 313-334.
- Horrow J. C. Protamine: a review of its toxicity . Anesth. and Analg. 1985. N 64. P. 348-361.
- Ischenko I.A., Milenkaya T.M. Effcacy of antioxidant usage in the treatment of diabetic retinopathy . Clin. Ophthalm. 2007. 8, N 3. P. 154-170.
- Kudriashov B.A., Shapiro B.F., Ulyanov A.M. Protamine sulfate-induced resistance to the hypoglycemic effect of insulin . Probl. Endokrinol. 1984. 30, N 1. R. 51-69.
- Kudrjashov B.A., Shapiro B.F., Ulyanov A.M. Role of heparin in realization of the hypoglycaemic action of insulin . Acta Phys. Hung. 1987. 69, N 2. R. 197-202.
- Pihlajam?ki, J.,H. Gylling, T.A Miettinen. Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men . J. Lipid Res. 2004. N 45. R. 507-512.
- Roep B.O., Atkinson M. Animal models have little to teach us about Type 1 diabetes: 1. In support of this proposal . Diabetologia. 2004. 47, N 10. R. 1650-1656.
- Scott, J.A., King, G.L. Oxidative stress and antioxidant treatment in diabetes . Annals N Y Acad. Sci.- 2004.- N 1031.- R. 204-213.
- Yamaguchi T, Terakado M., Horio F. Role of bilirubin as an antioxidant in an ischemia reperfusion of rat liver and induction of geme oxygenase . Biochem. Biophys. Res. Commun. 1996. N 223. P.129-135.