Advances in the clinical measurement of glucagon: from diagnosis to therapy.

ABSTRACT

Glucagon has many functions it promotes glucose production, fatty acid oxidation, thermogenesis, energy consumption, lipolysis, and myocardial contraction, and suppresses lipogenesis, appetite, and gastrointestinal motility. Which of these functions are physiological and which are pharmacological is not fully understood. Although the Mercodia sandwich ELISA provides significantly higher specificity of glucagon measurement than does conventional competitive RIA, it cannot provide accurate plasma glucagon values in the presence of elevated cross-reacting plasma glicentin. This occurs in patients post-pancreatectomy or bariatric surgery and in around 30% of outpatients suspected for glucose intolerance who have not had surgery. Thus, our newly developed sandwich ELISA with higher specificity and higher sensitivity than the Mercodia sandwich ELISA is needed for accurate measurements of plasma glucagon in diabetic patients. It is expected that the new sandwich ELISA will contribute to personalized medicine for diabetes by its use in clinical tests to accurately diagnose the conditions of diabetic patients in order to design better individual treatment strategies. Meanwhile, clinical trials are being conducted worldwide to apply glucagon/GLP-1 receptor dual agonists and glucagon/GLP-1/GIP receptor triagonists to the treatment of obesity, fatty liver, and diabetes. Most clinical trials have shown that both types of drugs have stronger effects on weight reduction, improving fatty liver, and glucose tolerance than do the single GLP-1 receptor agonists. Glucagon is expected to be used as a new diagnostic marker and in a new therapeutic strategy based on a true understanding of its physiological and pharmacological functions.