AGRP in IAH

The title of this blog contains two abbreviations, but important ones. IAH is impaired awareness of hypoglycaemia, and AGRP (or AgRP) is agouti-related protein. They are central in a paper just published by my talented colleague, Dr. Rita Varkevisser.

Learn how she summarizes the importance of this paper:

A compelling finding of this study was the association between agouti-related protein (AgRP) and impaired awareness of hypoglycaemia. AgRP is an important neuropeptide in energy homeostasis and is expressed in the adrenal gland and hypothalamus, specifically in the arcuate nucleus (ARC) and ventral hypothalamic nucleus (VMH) where central glucose sensing occurs. These glucose-sensing neurons in the ARC can influence glucose homeostasis through the activation of the autonomic nervous system and exert orexigenic effects through release of AgRP which inhibits MC4R neurons that stimulates food intake. The lower circulating plasma AgRP in individuals with IAH could suggest that these individuals could be less responsive to lower glucose levels. This may be due to threshold changes in the glucose-sensing neurons in the ARC and less hypothalamic-pituitary-adrenal (HPA) activation leading to less AgRP release from neuroendocrine cells in the adrenal medulla.

Another mechanism that may reduce AgRP release is the inhibition by other hormones such as insulin and leptin. Higher circulating levels of insulin usually leads to a reduction in appetite. In some individuals, hypothalamic insulin resistance may lead to increased food consumption despite higher circulating insulin levels. As a consequence of this insulin resistance, these individuals may be protected from hypoglycaemia, as the appetite suppression that would normally occur is no longer present. Although it is not yet clear how recurrent hypoglycaemia can influence glucose sensing and ARC/VMH mediated counterregulatory responses, further research into AgRP may help to elucidate the pathophysiology of IAH.

The mechanisms which dr. Varkevisser summarizers to play a role in IAH, are shown in this figure:

Dr. Varkevisser successfully defended her scientific thesis in November 2024. The full thesis with all her articles can be found on the University of Groningen website: https://research.rug.nl/en/publications/a-balancing-act-navigating-cardiovascular-vigilance-and-hypoglyca