Diabetes Pathophysiology

The myokine Interleukin-6 (IL-6) is a central focus point of the diabetes pathophysiology group. IL-6 is produced by immune cells and plays an important role in the immune system and has the ability to act in both a pro- and anti-inflammatory manner.

Skeletal muscle can produce and release IL-6 and physical activity (exercise) therefore leads to acutely increased levels of IL-6 in the circulation. In contrast, type 2 diabetes and obesity are associated with chronically elevated levels of IL-6.

In the diabetes pathophysiology group, we are interested in both the physiological as well as the pathophysiological roles of IL-6 in the regulation of energy metabolism. Moreover, we are interested in the role that IL-6 plays for physical performance and substrate choice (energy source).

Specifically, we study how IL-6 affects the endocrine function of the pancreas, i.e., insulin and glucagon secretion, as well as how IL-6 regulates the gastrointestinal function, the secretion of gastrointestinal hormones and the consequences on energy metabolism.

We have found that IL-6 regulates gastric emptying, that is the rate by which food leaves the stomach and enters the intestine. IL-6 delays this process which has beneficial effects on meal-induced increases blood glucose. Whether this effect of IL-6 is of importance to patients with type 2 diabetes is still unclear.

We are currently focusing on the following questions:

  1. How does IL-6 regulate gastric emptying and how does IL-6 regulate pancreatic insulin and glucagon secretion? Moreover, are the effects of IL-6 maintained in obese individuals and patients with type 2 diabetes?
  2. What is the role of IL-6 in exercise-induced adaptations to a physical training intervention? Does IL-6 play a role in the adaptations occurring in the gastro-intestinal system and in the endocrine pancreas?

Relevant literature

Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Ellingsgaard H, Hauselmann I, Schuler B, Habib AM, Baggio LL, Meier DT, Eppler E, Bouzakri K, Wueest S, Muller YD, Hansen AM, Reinecke M, Konrad D, Gassmann M, Reimann F, Halban PA, Gromada J, Drucker DJ, Gribble FM, Ehses JA, Donath MY. Nat Med. 2011 Oct 30;17(11):1481-9

Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control. Lang Lehrskov L, Lyngbaek MP, Soederlund L, Legaard GE, Ehses JA, Heywood SE, Wewer Albrechtsen NJ, Holst JJ, Karstoft K, Pedersen BK, Ellingsgaard H. Cell Metab. 2018 Jun 5;27(6):1201-1211.