The pig as an animal model for type 1 Diabetes Mellitus – with focus on carbohydrate and fat metabolism

Sammanfattning: Diabetes mellitus is an endocrine disorder affecting a range of different mammals, including dogs, cats, horses and humans. Worldwide, 347 million people have diabetes, and the disease is an increasing burden on the world’s poorest countries. The disease is characterised by chronic hyperglycaemia and afflicted individuals experience increased thirst, polyuria and weight loss, sometimes despite increased appetite. Diabetes mellitus is either insulin dependent or non-insulin dependent. In the present essay, focus is on insulin dependent, type 1 diabetes mellitus (T1DM); a condition where the insulin producing β-cells of the pancreas are destroyed and the insulin producing capacity diminished. Before insulin was discovered and became available as treatment, diabetes was a fatal disease. If T1DM is left untreated, the patient develops diabetic ketoacidosis, a potentially life-threatening condition. During treatment with insulin, there is a risk of insulin-induced hypoglycaemia, also a life-threatening complication. Animal models for diabetes mellitus are important to enable research to gain more information about the disease and to develop new and improved treatments. Rodent models are widely used for diabetes research. However, large animal models are very important tools for preclinical studies. The pig is a suitable large animal for diabetes studies. The physiology and metabolism of the pig resembles that of humans. Diabetes mellitus is a disease of the pancreas, and the size, shape and position of the porcine pancreas, resembles that of the human pancreas. Blood glucose concentrations range within the same levels as in humans and porcine insulin differ by only one amino acid compared to human insulin. Diabetes can occur spontaneously in mice and rats, but have to be experimentally induced in pigs. A type 1 diabetes mellitus like state can be induced with pancreatectomy or by injection of chemicals toxic to β-cells such as streptozotocin (STZ) or alloxan. In the present experiment it is showed that T1DM can be safely induced in domestic pigs at an i.v. STZ dose of 150 mg/kg b.w. The pigs develop clinical signs of diabetes mellitus such as polyuria/polydipsia and reduced weight gain compared to healthy individuals. Already two days post STZ treatment the pigs became hyperglycaemic and a significant (p<0.05) rise in serum non-esterified fatty acids (NEFA) concentrations and serum triglyceride concentrations was seen. Hyperglycaemia, hypertriglyceridaemia and elevated serum NEFA concentrations are also seen in diabetic humans. One week after initiation of insulin treatment, normoglycaemia is restored. One or three weeks after initiation of insulin treatment, serum concentrations of NEFA and triglycerides, respectively, are lowered to levels no different from that seen in the pigs before the induction of diabetes. This lowering of glucose, NEFA and triglyceride levels are also seen in insulin treated human patients with T1DM. From the present experiment it is concluded that a daily dosage of 1 IU/kg b.w. of short-acting insulin, divided by two times and given in direct connection to feeding is a satisfying treatment regimen. Both non-insulin treated and insulin treated STZ-diabetic pigs are brisk and vivid, and have good appetite.