Involvement of steatosis-induced glucagon resistance in hyperglucagonaemia
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Involvement of steatosis-induced glucagon resistance in hyperglucagonaemia. / Suppli, Malte P; Lund, Asger; Bagger, Jonatan I; Vilsbøll, Tina; Knop, Filip Krag.
I: Medical Hypotheses, Bind 86, 01.2016, s. 100-3.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Involvement of steatosis-induced glucagon resistance in hyperglucagonaemia
AU - Suppli, Malte P
AU - Lund, Asger
AU - Bagger, Jonatan I
AU - Vilsbøll, Tina
AU - Knop, Filip Krag
N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.
PY - 2016/1
Y1 - 2016/1
N2 - For more than a century type 2 diabetes 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, glucagon has also been recognised to play a significant role in type 2 diabetic pathophysiology. However, the mechanisms underlying disturbances in the regulation of glucagon remain unclear. Glucagon constitutes the primary stimulus for hepatic glucose production and, thus, upholds adequate blood glucose levels during fasting conditions. Many - but not all - patients with type 2 diabetes are characterised by inappropriately elevated plasma levels of glucagon contributing to their hyperglycaemic state. We believe that phenotypical dissimilarities within this group of patients may determine the presence and degree of hyperglucagonaemia. Results from our group show that both normoglycaemic individuals and patients with type 2 diabetes with non-alcoholic fatty liver disease (NAFLD) exhibit fasting hyperglucagonaemia compared to similarly grouped individuals without NAFLD. Therefore, we speculate that NAFLD - and not type 2 diabetes per se - is the main driver behind fasting hyperglucagonaemia. We hypothesise that in the majority of type 2 diabetic individuals hepatic sensitivity to glucagon is compromised due to hepatic steatosis, and that this provides a feedback mechanism acting at the level of pancreatic alpha cells, leading to elevated levels of glucagon. Here we present our hypothesis and propose a way to test it. If our hypothesis holds true, hepatic glucagon resistance would constitute a parallel to the obesity-induced insulin resistance in muscle and liver tissue, and underpin a central role for glucagon in the pathogenesis of type 2 diabetes. This would provide a crucial step forward in understanding the interaction between NAFLD and the alpha cell in the pathophysiology underlying type 2 diabetes.
AB - For more than a century type 2 diabetes 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, glucagon has also been recognised to play a significant role in type 2 diabetic pathophysiology. However, the mechanisms underlying disturbances in the regulation of glucagon remain unclear. Glucagon constitutes the primary stimulus for hepatic glucose production and, thus, upholds adequate blood glucose levels during fasting conditions. Many - but not all - patients with type 2 diabetes are characterised by inappropriately elevated plasma levels of glucagon contributing to their hyperglycaemic state. We believe that phenotypical dissimilarities within this group of patients may determine the presence and degree of hyperglucagonaemia. Results from our group show that both normoglycaemic individuals and patients with type 2 diabetes with non-alcoholic fatty liver disease (NAFLD) exhibit fasting hyperglucagonaemia compared to similarly grouped individuals without NAFLD. Therefore, we speculate that NAFLD - and not type 2 diabetes per se - is the main driver behind fasting hyperglucagonaemia. We hypothesise that in the majority of type 2 diabetic individuals hepatic sensitivity to glucagon is compromised due to hepatic steatosis, and that this provides a feedback mechanism acting at the level of pancreatic alpha cells, leading to elevated levels of glucagon. Here we present our hypothesis and propose a way to test it. If our hypothesis holds true, hepatic glucagon resistance would constitute a parallel to the obesity-induced insulin resistance in muscle and liver tissue, and underpin a central role for glucagon in the pathogenesis of type 2 diabetes. This would provide a crucial step forward in understanding the interaction between NAFLD and the alpha cell in the pathophysiology underlying type 2 diabetes.
KW - Anemia
KW - Diabetes Mellitus, Type 2
KW - Fatty Liver
KW - Glucagon
KW - Glucagon-Secreting Cells
KW - Humans
KW - Models, Biological
KW - Journal Article
U2 - 10.1016/j.mehy.2015.10.029
DO - 10.1016/j.mehy.2015.10.029
M3 - Journal article
C2 - 26547273
VL - 86
SP - 100
EP - 103
JO - Medical Hypotheses
JF - Medical Hypotheses
SN - 0306-9877
ER -
ID: 177063060