1.Preliminary Study on Construction Method of Type 1 Diabetes Model in Banna Miniature Pig
Kai LIU ; Yuqi HU ; Yatian GENG ; Wenjie CHENG ; Jing WANG ; Taiyun WEI ; Hongfang ZHAO ; Jiayu LI ; Deling JIAO ; Hongye ZHAO ; Hongjiang WEI
Laboratory Animal and Comparative Medicine 2024;44(4):384-392
Objective To construct a Type 1 diabetes model in miniature pigs and explore postoperative care strategies for effectively prolonging the survival time of the model pigs. Methods Seven Banna miniature pigs were selected for pancreatectomy. Glucose, vitamins, and antibiotics were administered for 3-5 days after surgery to aid recovery. Blood glucose and urine glucose levels were measured twice a day in the morning and evening to adjust insulin supplementation accordingly. The model pigs were observed daily and records were kept, including orexis, psychosis, weakness, skin ulcer, and feces and urine. Body weight was measured weekly until the death of the model animals. Based on the model pigs' condition, glucose injection and Ringer's lactate solution were administered to supplement nutrition and correct electrolyte imbalances. Results All seven Banna miniature pigs showed typical symptoms of diabetes: random blood glucose levels higher than 11.1 mmol/L after pancreatectomy, far exceeding the average blood glucose level of 6.0 mmol/L in normal pigs; positive urine glucose; and progressive weight loss. These features indicated the successful construction of Type 1 diabetes model. Additionally, Type 1 diabetic pigs that survived more than 8 weeks showed progressive hair loss and skin ulceration. Euthanasia was performed on model pigs when they were unable to stand or even eat independently, and pathological examination and HE staining were conducted on tissues collected from affected organs such as the liver, kidneys, and skin. Pathological sections revealed liver congestion, massive glycogen accumulation, ballooning degeneration of hepatocytes, and progressive liver fibrosis, along with glomerular congestion, vacuolar degeneration in renal tubular epithelial cells, proteinuria, dermal congestion, thinning of vascular walls, and varying degrees of parakeratosis and dyskeratosis in the liver, kidneys, and skin tissues due to prolonged hyperglycemia. The average survival time of the constructed Banna miniature pig diabetes model was 44 d, with a maximum survival time of 121 d. Conclusion Type 1 diabetes model can be constructed successfully in Banna miniature pigs through pancreatectomy. With meticulous postoperative care, a long-term Type 1 diabetes model with significant complications can be achieved, providing a stable large-animal model for Type 1 diabetes treatment strategies.