Glucoregulatory factors in canine hepatocellular carcinoma and leiomyosarcoma with non-islet cell tumour hypoglycaemia

Introduction: Hypoglycaemia caused by malignant tumours other than insulinoma is referred to as non-islet cell tumour hypoglycaemia (NICTH), which may be caused by hepatocellular carcinoma (HCC) and leiomyosarcoma (LMS) in veterinary medicine. However, the pathogenetic mechanism of NICTH remains unclear. Therefore, this study aimed to evaluate the gene-expression levels of glucoregulatory factors in canine HCC and LMS accompanied by hypoglycaemia.Materials & methods: Four patients (three with HCC and one with LMS) exhibiting hypoglycemia were included in the hypoglycemic (H) group, whereas ten patients not exhibiting hypoglycemia were in the non-hypoglycaemia (NH) group. The preoperative and postoperative blood glucose and serum insulin-like growth factor-2 (IGF-2) levels, as well as the expression of genes involved regulating blood glucose levels were analysed.Results: Compared with the NH group, the H group exhibited significantly decreased blood-glucose levels, which increased to normal values after surgery. Compared with the NH group, the H group exhibited significantly increased gene expression of insulin-like growth factor 1, IGF-2, and insulin-like growth factor binding protein 3 in the tumours. Conversely, expression of genes encoding glucoregulatory factors including insulin, gastric inhibitory polypeptide and glucagon was not observed. Serum IGF-2 levels were significantly higher in the H group compared with that in the control group (healthy dogs) and NH group. In two cases in the H group, serum IGF-2 levels decreased after tumour resection. Conclusion: These results suggest that NICTH development in dogs with HCC and LMS is mechanistically associated with IGF-2 overexpression and elevated serum IGF-2 levels.