Researchers from the University of Copenhagen are introducing a new biological concept in the fight against diabetes: glucagon resistance. Glucagon resistance or decreased sensitivity to the hormone glucagon increases the risk of type 2 diabetes. New research shows that glucagon resistance is particularly pronounced in people with fatty liver, and this may be the key to understanding the link between fatty liver and diabetes. Up to one in four Danes has an unhealthy accumulation of fat in the liver, also known as steathosis. Another name for the condition is non-alcoholic fatty liver disease (NAFLD). Nonalcoholic fatty liver disease is a spectrum of hepatic diseases associated with metabolic and cardiovascular disorders, such as obesity, insulin resistance, hypertension, dyslipidemia and type 2 diabetes. Fatty liver is rarely the cause of symptoms in itself, but people with fatty liver have an increased risk of developing diabetes. Exactly how the two diseases are linked has, however, so far been unknown.
Now, a new study from the Faculty of Health and Medical Sciences at the University of Copenhagen shows that people with fatty liver have reduced sensitivity to glucagon which increases the glucagon secretion and leads to increased amounts of glucagon in the blood. The same is seen in patients with type 2 diabetes, the vast majority of whom have increased fat in the liver. The reduced glucagon sensitivity means that the secretion of glucagon is increased via a so-called feedback system between the liver and the pancreas. An elevated level of glucagon is undesirable as it increases sugar production in the liver and thus creates a high blood sugar level. With the study, the researchers are introducing an entirely new concept within the field of diabetes: glucagon resistance. They believe that the concept is so fundamental to the understanding of diabetes that it should not be limited to laboratories and research environments.
Nicolai Wewer Albrechtsen, Assistant Professor at the Novo Nordisk Center for Protein Research and at the Department of Clinical Biochemistry, explained: “Glucagon resistance is an entirely new biological concept that we will include in the future teaching of medical students, just as we do today with insulin resistance. The decreased glucagon sensitivity may help to explain the connection between fatty liver and type 2 diabetes. And with new knowledge come new opportunities. If you can detect decreased glucagon sensitivity, you can start treatment earlier. That way, you can stop the glucagon level and thus the blood sugar from running wild. Our study points to a new biomarker (the glucagon-alanine index) that may be useful in identifying persons with impaired glucagon sensitivity. If we can detect glucagon resistance from a blood test, we can start treatment early and thus prevent the development of type 2 diabetes”.
The treatment for fatty liver consists primarily of weight loss and a carbohydrate-poor diet, which will limit the amount of fat in the liver. With these new notions, it might also include drugs that go in and inhibit the hormone glucagon.
- Edited by Dr. Gianfrancesco Cormaci, PhD; specialist in Clinical Biochemistry.
Scientific references
Winther-Sørensen M, Galsgaard K et al. Mol Metab. 2020 Sep 13:101080.
Bisgaard Bengtsen M et al. J Clin Endocrinol Metab. 2020 Sep 14:dgaa645.
Papazafiropoulou AK, Melidonis A et al. Curr Pharm Des. 2020 Sep 9.
