Gut hormones - Novel tools in the treatment of insulin resistance

Abstract

Type 2 diabetes mellitus has now become a global epidemic. The past decade hormones from the gastrointestinal tract have gained much interest as potential new therapeutic drugs in the battle against this disease. Gut peptides play an important role in regulating food intake and energy homeostasis. In addition, they are able to impact on insulin sensitivity. In the present thesis we focused on modulation of insulin sensitivity by different gut hormones or their analogues. By means of the hyperinsulinemic euglycemic clamp technique we show that these gut hormones beneficially impact on insulin resistance. In addition, we show that these gut hormones can decrease body weight and inhibit lipid production, which are promising results since insulin resistance is a complex disease and is associated with obesity and cardiac disease. Also, we show that the hormone GLP-1 reduces endogenous insulin resistance via the brain. Over the past decade a growing amount of evidence indicates that the gut-brain axis is a key player in the control of glucose homeostasis. Elucidating more precisely the molecular events in the brain that underlie the effects of these hormones could lead to the identification of new (or improved) therapeutic agents.