Role of Glucagon in the Pathophysiology of Diabetes: Hypothesis Around a Primary Causal Relationship

Glucagon is another hormone involved with blood sugar control. It is made by the alpha cells in the pancreas and causes blood sugar levels to rise by stimulating the breakdown of glycogen in the liver. Accumulating evidence from over 4 decades of research into the role of glucagon in exacerbating diabetes, both type 1 and 2, is now suggesting that glucagon could be a primary cause of, rather than a consequence of, diabetes a major shift in thinking about diabetes. This study suggests that an excess of glucagon is a basic feature of diabetes, and therefore, glucagon suppression may present therapeutic advantages over insulin therapy alone. Multiple mechanisms and lines of evidence, both preclinical and clinical, support this theory and lead to correction or improvement of diabetes in preclinical models. Also, this article (and several previous reports) has emphasized the importance of the close physical proximity of glucagon and insulin producing cells within the pancreas, highlighting that the two cell types cross-talk to regulate a tight glycemic balance.

Reference:

Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover, J Clin Invest 2012, 122(1):4-12

Ramifications for Individuals with Type 1 Diabetes:

Insulin monotherapy remains the main (and mostly only) form of T1D management, but it addresses only part of the disease process. Other pathways important to controlling blood sugar levels that are compromised, broken or completely missing could be fixed by adjunctive treatments. Such combination therapy (for example using both insulin and glucagon to complement each other) should provide better glycemic and metabolic control in the near term, and potentially alleviate the burden of a majority of complications arising from years of poor control.

JDRF Involvement:

This work was not supported by JDRF.