Glucose Metabolism and Regulation: Beyond Insulin and Glucagon

Insulin and glucagon are potent regulators of glucose metabolism. For decades, we have viewed diabetes from a bi-hormonal perspective of glucose regulation. This perspective is incomplete and inadequate in explaining some of the difficulties that patients and practitioners face when attempting to tightly control blood glucose concentrations. Intensively managing diabetes with insulin is fraught with frustration and risk. Despite our best efforts, glucose fluctuations are unpredictable, and hypoglycemia and weight gain are common. These challenges may be a result of deficiencies or abnormalities in other glucoregulatory hormones. New understanding of the roles of other pancreatic and incretin hormones has led to a multi-hormonal view of glucose homeostasis.

Full Text :


Eating disorders – Amylin deficiency in type 1 diabetes can lead to increased feelings of hunger?


Patients with type 1 diabetes also lose amylin production – a hormone responsible for gastric emptying and associated with feelings of fullness – that can also lead to increased feelings of hunger,” Dr. Young-Hyman said.


Amylin & Diabetes



It was held for a long time by the medical community that there were only two hormones responsible for maintaining blood glucose within physiologically normal ranges. These hormones were insulin, which controls the rate of glucose disappearance in the circulation after eating; and glucagon, which controls the rate of glucose release from the liver into the circulation while we are sleeping. However, in 1987 another pancreatic hormone was discovered and it has greatly impacted the understanding of glycemic control and diabetes management. This hormone is amylin.

What is Amylin?

Amylin is a pancreatic hormone synthesized by beta-cells, the very same cells responsible for the synthesis of insulin. In individuals without diabetes, it has been observed that insulin and amylin have the same parallel pattern of secretion throughout the day so that when insulin levels are high after a meal, so are amylin levels and vise versa. In diabetic individuals, amylin secretion will be consistent with the body’s own insulin secretion. Therefore, in type 1 diabetes, since there is an absolute deficiency of insulin due to beta-cell destruction, there will be an absolute deficiency of amylin production as well. In type 2, there is a marked decrease in the secretion of this hormone.

Physiological Role of Amylin

Physiologically speaking, amylin is a neuroendocrine hormone with several sites of action all working together to reduce post-meal glucose levels. In animal studies it has been shown that the actions of amylin are largely exerted via the central nervous system by the hormone attaching itself to specific receptors in the brain. It then works to suppress glucagon, promotes a feeling of fullness while eating, and slows down the emptying of food contents from the stomach to the small intestines for absorption into the body. In short, while insulin promotes the disappearance of glucose from the circulation, amylin functions to control the rate of appearance of glucose into circulation.

Current Options for Meeting Glycemic Goals

Therapies for meeting glycemic goals in diabetes have addressed the various physiological characteristics of diabetes. For example, some therapies using the sulfonylurea and glinide drugs focus on simulating insulin secretions in individuals with deficient insulin action. Other therapies include reducing peripheral insulin resistance with the thiazolidinediones, decrease excessive glucose output from the liver with the biguanides, or decrease glucose absorption from the intestines with alpha-glucosidase inhibitors and bile acid sequestrants. However, with the discovery of amylin, healthcare providers now have the ability to improve an individual’s glycemic management even further.

Amylin and Post-Meal Glycemic Control

As mentioned earlier, amylin works to suppress glucagon, the pancreatic hormone responsible for maintaining blood glucose within normal ranges while we rest. In the diabetic individual, glucagon levels are not well controlled, which can lead to persistent elevated blood sugars even when not eating food. While insulin suppresses glucagon secretion and action, amylin has been demonstrated to be much more effective at doing this. In studies of type 1 and type 2 diabetics, increases in glucagon levels were observed even when insulin was appropriately administered to control glycemic levels after a meal. This reinforces the synergistic relationship between insulin and amylin in controlling blood glucose levels.

Implications for Diabetes Management

The amylin analog, Pramlintide, is currently approved for the treatment of typev1 or typev2 diabetes, and it is injected just prior to meals. The addition of amylin to a medical regimen can improve blood glucose management from day to day, thus helping to avoid the chronic complications associated with elevated blood glucose levels.
Read more: