Involvement of steatosis-induced XXXX resistance in hyperglucagonaemia.

@entity1 @entity15669 @entity6 @entity1560 @entity28 @entity1561 @entity164 @entity413
UNASSIGNED: For more than a century @entity164 2 @entity6 has been looked upon mainly as an insulin-related disease and it is well-acknowledged that insulin resistance and beta cell dysfunction play important roles in the pathophysiology of the disease. During the last couple of decades, @entity15669 has also been recognised to play a significant role in @entity164 2 @entity6 pathophysiology. However, the mechanisms underlying disturbances in the regulation of @entity15669 remain unclear. Glucagon constitutes the primary stimulus for hepatic @entity413 production and, thus, upholds adequate blood @entity413 levels during fasting conditions. Many - but not all - @entity1 with @entity164 2 @entity6 are characterised by inappropriately elevated plasma levels of @entity15669 contributing to their hyperglycaemic state. We believe that phenotypical dissimilarities within this group of @entity1 may determine the presence and degree of hyperglucagonaemia. Results from our group show that both normoglycaemic individuals and @entity1 with @entity164 2 @entity6 with @entity1561 ( @entity1561 ) exhibit fasting hyperglucagonaemia compared to similarly grouped individuals without @entity1561 . Therefore, we speculate that @entity1561 - and not @entity164 2 @entity6 per se - is the main driver behind fasting hyperglucagonaemia. We hypothesise that in the majority of @entity164 2 @entity6 individuals hepatic sensitivity to @entity15669 is compromised due to @entity1560 , and that this provides a feedback mechanism acting at the level of pancreatic alpha cells, leading to elevated levels of @entity15669 . Here we present our hypothesis and propose a way to test it. If our hypothesis holds true, hepatic @entity15669 resistance would constitute a parallel to the @entity28 -induced insulin resistance in muscle and liver tissue, and underpin a central role for @entity15669 in the pathogenesis of @entity164 2 @entity6 . This would provide a crucial step forward in understanding the interaction between @entity1561 and the alpha cell in the pathophysiology underlying @entity164 2 @entity6 .
