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.

Keywords: Diabetes mellitus; growing pigs; high-energy diet; streptozotocin; transcription factor 7-like 2 genotype.

Figure 1. Fasting (A) and postprandial (B) blood glucose levels in growing pigs with C/C (diabetes protective) and T/T (diabetes risk) genotypes of transcription factor 7-like 2 after STZ/HFHE treatment. Horizontal lines in A (7.0 mmol/L) and in B (11.1 mmol/L) indicate the diagnostic criteria for diabetes. Means at the same time marked by different letters differ significantly (P<0.05).

Figure 2. Blood glucose responses in oral glucose tolerance tests in growing pigs with C/C and T/T variants for transcription factor 7-like 2 at the 2^nd (A) or 4^th (B) week after diabetic induction. The horizontal broken line (11.1 mmol/L) is the postprandial glucose guideline for the diagnosis of diabetes. Asterisks at the same time indicate significant differences between the T/T and control groups (P<0.05).

Figure 3. Changes in the fasting (A) and postprandial (B) plasma insulin content (1 IU=6.945 pmol/L) of growing pigs with C/C and T/T genotypes for transcription factor 7-like 2 after diabetic inductions. Means at the same time marked by different letters differ significantly (P<0.05).

Figure 4. Homeostatic model assessment-insulin resistance (HOMA-IR) index of growing pigs with the C/C and T/T genotypes of transcription factor 7-like 2 after diabetic induction. Means with different letters in the same week differ significantly (P<0.05).

Figure 5. Comparisons of the insulin positive area (IPA) of growing pigs with C/C and T/T genotypes of transcription factor 7-like 2 12 weeks after diabetic induction. Images of the IPAs in the pancreas samples are shown in (A). a1 to a3 are the controls, b1 to b3 are C/C genotype and c1 to c3 are T/T genotype. Yellow bars represent 100 mm. (B). Counts and comparison of the IPAs in the pancreas samples of C/C and T/T carriers are shown in B. Columns in the same size group with different letters differ significantly (P<0.05).