Metformin reduces insulin resistance and the tendency toward hyperglycaemia and dyslipidaemia in dogs with hyperadrenocorticism.

Hypercortisolism induces a state of insulin resistance that can occur concurrently with fasting hyperglycaemia, dyslipidaemia and diabetes mellitus. Metformin reduces hepatic glucose production and insulin resistance of the skeletal muscle and adipose tissue. The aim of this study was to evaluate the effects of metformin on the control of metabolic disorders of dogs with hyperadrenocorticism (HAC). Twenty-three dogs with HAC were randomly divided into two groups, consisting of a control group and a metformin group (10 mg metformin/kg/12 h). Both groups received the same treatment for HAC. At baseline and 3 months, blood glucose, total cholesterol, triglycerides and insulin concentrations, in addition to urinary cortisol:creatinine ratio, Homeostatic Model Assessment (HOMA) for insulin sensitivity and ß-cell function were measured. Dogs treated with metformin showed significantly reduced glycaemia, cholesterolaemia and triglyceridaemia. They also presented reduced hyperinsulinism and insulin resistance, as well as improved pancreatic ß-cell function. The implementation of metformin as an adjuvant therapy is effective for the normalisation of metabolic disorders of dogs with HAC.

Overexpression of 11ß-hydroxysteroid dehydrogenase 1 in visceral adipose tissue and underexpression of endothelial nitric oxide synthase in the adrenal cortex of dogs with hyperadrenocorticism.

11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) is an enzyme that activates cortisone into cortisol in tissues. Alterations in this enzyme are related to the development of metabolic syndrome, obesity and hyperadrenocorticism (HAC). Endothelial nitric oxide synthase (eNOS) produces nitric oxide and is related to the regulation of adrenal steroidogenesis. The aim of the study was to evaluate 11ß-HSD1 and eNOS expression in dogs with HAC. Visceral adipose tissue samples were taken to evaluate 11ß-HSD1 expression by immunohistochemistry and western blotting. In parallel, adrenal gland samples were collected to evaluate eNOS expression by immunohistochemistry. 11ß-HSD1 expression was significantly higher in the adipocytes of dogs with HAC than in those of the control dogs. eNOS expression in the adrenal cortex (zona fasciculata) was significantly lower in the dogs with HAC than in the control dogs. 11ß-HSD1 overexpression and eNOS underexpression could play a role in the maintenance of hypercortisolism in dogs with HAC.