Diabetes mellitus in dogs (Proceedings)
The endocrine pancreas is comprised of groups of cells (islets of Langerhans) scattered throughout the acinar parenchyma of the gland in a ratio of approximately 90% acinar cells (exocrine function) to 10% of islet cells (endocrine function). The pancreas is a boomerang-shaped organ comprised of two "wings" (duodenal and omental) in the cranial right quadrant of the abdomen.
The islets contain 4 types of cells which synthesize different hormones. The most numerous cells are the beta cells which produce insulin. The alpha cells produce glucagons; the D cells produce somatostatin and the PP cells produce pancreatic polypeptide. The venous drainage from the pancreas is via the hepatic portal vein, thus the liver is the recipient of the major physiologic effects of these hormones.
Normal physiologyAfter a meal, glucose and other nutrients are absorbed from the GI tract and into the circulation. During this process, insulin is secreted by the beta cells of the pancreas. Other stimuli of insulin secretion include: increased concentration of amino acids and GI hormones During this phase insulin produces the movement of glucose into the target cells (via insulin-specific receptors) for metabolism of energy and storage of glycogen and fat. The net physiologic effect of insulin is to lower blood glucose, store fat into adipose tissue and synthesize proteins. Simultaneously, glucagon is secreted by the alpha islet cells in response to increased amino acid concentration. Glucagon is a potent insulin antagonist, by stimulating glucogenolysis and gluconeogenesis, with a net effect being an increase in blood glucose concentration. This bi-hormonal effect of both insulin and glucagons prevents hypoglycemia when a dog or cat ingests a meal that is high in protein and low in carbohydrate.
This increase in blood glucose concentration produces a negative feedback effect upon the pancreatic alpha cells shutting off further secretion of glucagon. Insulin is required for the glucose to enter the alpha islet cells in order to inhibit glucagons secretion. This explains why glucagons levels are elevated in diabetic cats and dogs that have and absolute insulin deficiency despite elevated glucose levels. (the "bi-hormonal" hypothesis of diabetes mellitus).
Several hours after eating, during the post-absorptive state, there is a drop blood glucose concentration, causing a reduction in insulin and increase in glucagon secretion. The glucagon stimulates gluconeogenesis with subsequent increase in blood glucose, in order to maintain it in a normal range. The major stimulus for the glucagons secretion is hypoglycemia.
Insulin is the most important hormone that stimulates free fatty acid (FFA) storage in adipose tissue. During prolonged periods of starvation or uncontrolled diabetes mellitus FFA's are mobilized because blood insulin levels are reduced and glucagon levels are increased.
Glucose is the primary source of energy in nervous tissue which can only store glycogen for a few minutes, thus it is essential that blood be maintained in the normal range. If moderate to severe hypoglycemia occurs glucagons and epinephrine are secreted rapidly (the amount of secretion depends upon the rate and magnitude of hypoglycemia). Epinephrine will inhibit insulin secretionand stimulate glycogenolysis which increases blood glucose. In addition STH and glucocorticoids are secreted approximately 30 minutes after glucagon and epinephrine and will inhibit glucose utilization and stimulate gluconeogenesis. These physiologic events are vital to maintain normoglycemia in the brain.
This common endocrinopathy results from a relative or absolute deficiency of insulin and overproduction of glucagon, resulting in persistent hyperglycemia. Nearly 100% of affected dogs and 50-70% of affected cats are insulin dependent. Its incidence is 2 out of 1000 dogs seen every year and is more common in females (approximately 75% of all cases). Castrated male dogs are at a greater risk than intact male dogs. Diabetes mellitus can occur at any age (< 1 year yo 15 years) but thr peak ages of incidence are 7 to 11 years. The commonly breeds affected include: poodles, dachshunds, keeshounds, cairn terriers, miniature schnauzers, schipperkes, miniature pinschers and English springer spaniels. Breeds that are at a reduced risk to develop diabetes mellitus include: collies, German Shepherds, boxers, Pekinese and cocker spaniels.