Blood glucose regulation in healthy dogs and cats
To understand how and why diabetes develops, it is necessary to get first an explanation on the mechanisms of blood glucose regulation in healthy animals. Glucose is the primary source of energy for the body. The liver, the brain, the digestive system and skeletal muscles are the main glucose consumers. All other organs need glucose, but in lesser amounts. Liver plays a special role in glucose homeostasis: it stocks or releases glucose according to the needs of the organism. It captures between 30 and 50% of the sugar brought by the meals. In the healthy dog or cat, the concentration of blood glucose is maintained stable through a tight regulation. Numerous hormones are involved, but two of them are prominent. They both are secreted in the pancreas. They play a symmetrical role:
- Insulin lowers blood glucose concentration
- Glucagon brings blood glucose concentration up
Insulin is an hormone produced by the β cells of the pancreas within the islets of Langerhans. The islets of Langerhans are the region in the pancreas where all the pancretic hormones are synthetized. Insulin secretion is triggered by elevated blood glucose levels that it tends to compensate. This is a classical feedback system involving two different mechanisms that both tend to lower glucose level. Insulin induces the conversion of glucose into glycogen (glycogenesis).
Glycogen is a long chain of glucose molecules. Glycogen is stored in the liver, muscles and, to a lesser extent in the kidneys. It serves as reserve of energy and can be readily converted back to glucose when needed. As a result, insulin secretion, by stimulating glycogen formation, reduces blood glucose. Glucose is not readily available for the cells. It needs insulin and GLUT proteins (facilitative glucose transporters molecules) to get through the impermeable cell membranes. By facilitating the use of glucose by the cells, insulin contributes to lowering glucose levels in the blood.
Glucagon is produced by the α cells of the pancreas. It counterbalances the effects of insulin. Glucagon increases glucose levels in response to low normal glucose levels or hypoglycemia. It helps break down glycogen into glucose and limits the production of glycogen in the liver. Insulin inhibits glucagon secretion.
Other regulators of blood glucose
Insulin was discovered in the 1920s and remained for a long time the main treatment for treating diabetes. In the 1950s, glucagon role in hepatic glucose production was elucidated. Since then the roles of other hormones in blood glucose regulation was unveiled: amylin, GLP-1 peptide, GIP peptide, epinephrine, cortisol, growth hormone and somatostatin. The kidneys also are involved in the regulation of glycemia.
As insulin, amylin is secreted by the β cells of the pancreas. Amylin has a double role:
- Amylin acts as a hormone by helping lower blood sugar levels: 1) it suppresses postprandial glucagon secretion; and 2) it slows down the stomach emptying and thus the speed at which the nutrients (including carbohydrates) are digested in the intestine.
- Amylin, also called Islet Amyloid Polypeptide (IAPP), has amyloidogenic properties: it aggregates and forms amyloid fibrils. The deposition of amyloid fibrils (amyloidosis) progressively destroys the β cells. Amyloidosis is responsible for impaired insulin secretion in type 2 diabetes
GIP & GLP-1 are peptide (small proteins) hormones triggered by ingested food, especially if it is rich in fat and sugars. They stimulate the secretion of insulin. GLP-1, in addition, inhibits glucagon and, as amylin, slows down food progression in the digestive tract.
Epinephrine (= adrenaline) is synthesized in the adrenal glands. It is released in the blood when stress and strong emotions occur. It is the stress hormone involved in the “fight or flight” response. Among many other effects, epinephrine elevates blood glucose levels. It induces glucose production by the liver, inhibits insulin secretion and hinders glucose utilization within the cells.
Cortisol, as epinephrine, is produced in the adrenal glands, in response to stress. It increases blood sugar levels by promoting the breaking down of glycogen in glucose.
The growth hormone, also called somatotropin, is secreted in the pituitary gland. It counteracts the effects on insulin, within the cells. It inhibits glucose oxidation and decreases the rate at which cells use glucose.
Somatostatin is a hormone that is produced in the hypothalamus and in the pancreas. It inhibits the growth hormone, glucagon and insulin. Experiments show that it tends to lower blood glucose in diabetic patients.
Kidneys are increasingly considered as an important actor in blood glucose regulation. As the liver they uptake or release glucose in the blood circulation, in response to the body energy needs. The kidneys also eliminate in the urine the excess of glucose in the blood when it reaches the threshold of 180 mg/dL (10 mmol/L) in dogs or 290mg/dL (16 mmol/L) in cats.