Growing pigs developed different types of diabetes induced by streptozotocin depending on their transcription factor 7-like 2 gene polymorphisms
- 11 Downloads
The different polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene promote variances in diabetes susceptibility in humans. We investigated whether these genotypes also promote differences in diabetic susceptibility in commercial pigs. Growing pigs (Landrace, both sex, 50–60 kg) with the C/C (n=4) and T/T (n=5) TCF7L2 genotypes were identified and intravenously injected with streptozotocin (STZ, 40 mg/kg) twice in weekly intervals, then a high-energy diet was offered. Oral glucose tolerance tests, blood analyses and the homeostasis model assessment-insulin resistance (HOMA-IR) index calculations were performed. The animals were sacrificed at the end of 12 weeks of treatment to reveal the pancreas histomorphometry. The results showed that all of the treated pigs grew normally despite exhibiting hyperglycemia at two weeks after the induction. The glycemic level of the fasting or postprandial pigs gradually returned to normal. The fasting insulin concentration was significantly decreased for the T/T carriers but not for the C/C carriers, and the resulting HOMA-IR index was significantly increased for the C/C genotype, indicating that the models of insulin dependence and resistance were respectively developed by T/T and C/C carriers. The histopathological results illustrated a significant reduction in the pancreas mass and insulin active sites, which suggested increased damage. The results obtained here could not be compared with previous studies because the TCF7L2 background has not been reported. Growing pigs may be an excellent model for diabetic in children if the animals are genetically pre-selected.
KeywordsDiabetes mellitus growing pigs streptozotocin high-energy diet transcription factor 7-like 2 genotype
- 6.van der Kroef S, Noordam R, Deelen J, Akintola AA, Jansen SW, Postmus I, Wijsman CA, Beekman M, Mooijaart SP, Slagboom PE, van Heemst D. Association between the rs7903146 Polymorphism in the TCF7L2 Gene and Parameters Derived with Continuous Glucose Monitoring in Individuals without Diabetes. PLoS One 2016; 11(2): e0149992.PubMedPubMedCentralCrossRefGoogle Scholar
- 12.National Research Council. Nutrient requirements of swine, 11th ed. The National Academies Press, Washington, D.C., 2011; pp 208–238.Google Scholar
- 14.National Research Council. Guide for the care and use of laboratory animals, 8th ed. The National Academies Press, Washington, D.C., 2011; pp 41–76.Google Scholar
- 18.Furman BL. Streptozotocin-Induced Diabetic Models in Mice and Rats. Curr Protoc Pharmacol 2015; 70: 1–20.Google Scholar
- 30.Dabelea D, Mayer-Davis EJ, Saydah S, Imperatore G, Linder B, Divers J, Bell R, Badaru A, Talton JW, Crume T, Liese AD, Merchant AT, Lawrence JM, Reynolds K, Dolan L, Liu LL, Hamman RF; SEARCH for Diabetes in Youth Study. Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA 2014; 311(17): 1778–1786.CrossRefGoogle Scholar
- 31.Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L, Imperatore G, Linder B, Marcovina S, Pettitt DJ, Pihoker C, Saydah S, Wagenknecht L; SEARCH for Diabetes in Youth Study. Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002–2012. N Engl J Med 2017; 376(15): 1419–1429.PubMedPubMedCentralCrossRefGoogle Scholar
- 32.Takamoto I, Kubota N, Nakaya K, Kumagai K, Hashimoto S, Kubota T, Inoue M, Kajiwara E, Katsuyama H, Obata A, Sakurai Y, Iwamoto M, Kitamura T, Ueki K, Kadowaki T. TCF7L2 in mouse pancreatic beta cells plays a crucial role in glucose homeostasis by regulating beta cell mass. Diabetologia 2014; 57(3): 542–553.PubMedCrossRefGoogle Scholar
- 35.Yang T.S. Wild to domestic: body and organ size matter fitness in boars. In: Jenkins OP (ed) Advances in Zoology Research. Nova Science Publishers, Inc., NY, 2012; pp 187–200.Google Scholar
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://doi.org/creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.