How is Amylin, type 2 diabetes, related to Cushing syndrome?

 

What is amylin deficiency?

People with diabetes have a deficiency in the secretion of amylin that parallels the deficiency in insulin secretion, resulting in an excessive inflow of glucose into the bloodstream during the postprandial period.

 

Normal plasma levels of amylin vary from 4 pmol/L (fasting) to 25 pmol/L (postprandially).

Where is amylin found?

Amylin, also known as islet amyloid–associated peptide, is a 37–amino acid hormone produced in islet beta cells and in scattered endocrine cells in the stomach and the proximal small intestine.

 

What are the sources of amylin?

The primary known source of amylin in the body is the pancreas, and although amylin can cross the blood-brain barrier [133, 134], does circulating, pancreatic-derived amylin actually access these sites to cause hypophagia and weight loss?

What inhibits amylin?
In this study, we demonstrated that two inhibitors, lipoic acid and ascorbic acid, significantly inhibited amylin aggregation.

 

What stimulates release of amylin?

Amylin, (or islet amyloid polypeptide; IAPP), a 37-amino acid peptide hormone, is released in response to nutrients, including glucose, lipids or amino acids. Amylin is co-stored and co-secreted with insulin by pancreatic islet β-cells.

 

What inhibits amylin?

In this study, we demonstrated that two inhibitors, lipoic acid and ascorbic acid, significantly inhibited amylin aggregation. https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.7b01009

Is Amylin related to Cushing syndrome?

Amylin, also known as islet amyloid polypeptide (IAPP), is a hormone that is co-secreted with insulin by the pancreatic beta cells. It has a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels. Amylin deposition in the pancreas is characteristic of type 2 diabetes, where it forms amyloid plaques and can contribute to the dysfunction of pancreatic beta cells.

Cushing's syndrome, on the other hand, is characterized by an overproduction of cortisol by the adrenal glands, often due to an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma (Cushing's disease), an adrenal tumor, or an ectopic ACTH-producing tumor. The high levels of cortisol in Cushing's syndrome lead to a variety of symptoms including obesity, hypertension, diabetes, and others.

The relationship between amylin and Cushing's syndrome is indirect and lies primarily in the area of glucose metabolism. In Cushing's syndrome, the excess cortisol can lead to insulin resistance, which in turn can contribute to hyperglycemia and the development of diabetes mellitus. In the context of diabetes or insulin resistance, there could be alterations in the secretion or action of amylin, similar to what is seen in type 2 diabetes.

However, amylin itself is not a direct cause or a hallmark of Cushing's syndrome, and there isn't a known direct link between amylin and the etiology of Cushing's syndrome. The connection is more related to the fact that both involve endocrine pathways and both can impact glucose metabolism, albeit through different mechanisms. In clinical practice, the management of Cushing's syndrome focuses on the underlying cause of cortisol excess, whereas issues related to amylin would be addressed in the context of managing diabetes or insulin resistance, which may be a consequence of long-standing Cushing's syndrome.