Growing pigs developed different types of diabetes induced by streptozotocin depending on their transcription factor 7-like 2 gene polymorphisms

Abstract

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.

Porcine models for studying complications and organ crosstalk in diabetes mellitus

“…The low level of GLUT2 expression in porcine beta cells compared to other species like rats and primates (Dufrane et al 2006), high variation in individual sensitivity to STZ treatment and a substantial degree of beta cell regeneration in young animals make STZ treatment a rather difficult approach to induce DM in the pig. A potential source of interindividual variation in pigs in the response to STZ is polymorphism in TCF7L2 (Tu et al 2018), the most prominent type 2 diabetes susceptibility gene in humans (Grant 2019).…”