Current approach to insulinoma in ferrets (Proceedings)
Pancreatic islet beta cell tumors secrete high levels of insulin and cause hypoglycemia. Clinical signs include lethargy, weight loss, weakness, ptyalism, bruxism, seizures, and death. Treatment modalities include medical therapy, chemotherapy, surgery, and dietary changes. The etiology of insulinoma is unknown, however a nutritional hypothesis has recently been offered along with a prevention strategy based upon feeding a more natural, archetypal diet.
Insulinoma is by far the most common neoplasm in ferrets, with a reported incidence of approximately 25% of neoplasms diagnosed. It is commonly seen in middle-aged to older ferrets. Although most affected ferrets begin exhibiting clinical signs around 4 years of age, it has been reported in ferrets as young as 2 weeks of age. It is likely that islet cell tumors exist subclinically for months or years before symptoms occur. Both sexes may be affected, but there are conflicting reports as to whether males are slightly overrepresented.Insulinomas appear to occur regionally. They are uncommon among ferrets in Europe, New Zealand and Australia. The majority of ferrets from these areas are fed a low-carbohydrate diet of meat scraps, poultry scraps, and/or fish scraps, and sugary treats are not provided. By contrast, insulinoma is common in the United States, where the majority of ferrets are fed dry kibble containing 10-45% carbohydrate, and many are fed treats that contain sugar. Finkler hypothesizes that such excessive carbohydrate intake stimulates excessive insulin production by the pancreas and results in compensatory hyperplasia. He postulates that lifelong stimulation of pancreatic beta cells leads to a hyperinsulinemic "preinsulinoma" state and eventually to the development of beta cell neoplasia.
Domestic pet ferrets in the U.S. are supplied by a small number of breeders, thus limiting their genetic diversity, and suggesting that the development of insulinomas may have a genetic component.
The pancreas plays a major role in glucose, lipid, and protein metabolism through the balance of its two major hormones, insulin and glucagon. Insulin, a polypeptide produced by beta islet cells, is released when levels of glucose, amino acids, and free fatty acids are increased in the blood. In the case of a sudden increase in the blood glucose level, the plasma insulin level can increase almost 10 fold within minutes. Insulin then causes a rapid uptake of glucose into peripheral tissues and promotes the storage of glucose in the muscle and liver. Additionally, insulin inhibits hepatic gluconeogenesis and glycogenolysis, and promotes the conversion of excess glucose into fatty acids. The net effect of all these processes is a decrease in blood glucose levels. Glucagon is secreted by alpha cells in response to decreasing glucose levels and is involved in effects that are exactly opposite to those of insulin, namely, an increase in the blood glucose level.
Beta cell tumors produce their effects through the overproduction of insulin. Insulin is released when levels of glucose, amino acids, and free fatty acids are increased in the blood. Insulin then causes a rapid uptake and storage of glucose by cells, inhibits hepatic gluconeogenesis and glycogenolysis, and promotes the conversion of excess glucose into fatty acids. The net effect of all these processes is a decrease in blood glucose levels. Insulinomas secrete indiscriminately and are not responsive to inhibitory stimuli such as hypoglycemia or hyperinsulinemia. In addition, rapidly increasing levels, even in the presence of low blood glucose concentration, can stimulate excessive insulin release from these tumors, causing a profound rebound hypoglycemia. Although local tumor recurrence is common, metastasis to other organs is not. This finding is in contrast to insulinomas found in dogs, which are usually malignant and metastatic. When insulinoma metastasis does occur in a ferret, the regional lymph nodes, liver and spleen are the organs most commonly involved.