title: Glucagon - the new 'insulin' in the pathophysiology of diabetes.
abstract: OBJECTIVE
  Autoimmune destruction of the β cells is considered the key abnormality in type 1 diabetes mellitus and insulin replacement the primary therapeutic strategy. However, a lack of insulin is accompanied by disturbances in glucagon release, which is excessive postprandially, but insufficient during hypoglycaemia. In addition, replacing insulin alone appears insufficient for adequate glucose control. This review focuses on the growing body of evidence that glucagon abnormalities contribute significantly to the pathophysiology of diabetes and on recent efforts to target the glucagon axis as adjunctive therapy to insulin replacement.
  
  
  RESULTS
  This review discusses recent (since 2013) advances in abnormalities of glucagon regulation and their link to the pathophysiology of diabetes; new mechanisms of glucagon action and regulation; manipulation of glucagon in diabetes treatment; and analytical and systems biology tools to study glucagon regulation.
  
  
  CONCLUSIONS
  Recent efforts 'resurrected' glucagon as a key hormone in the pathophysiology of diabetes. New studies target its abnormal regulation and action that is key for improving diabetes treatment. The progress is promising, but major questions remain, including unravelling the mechanism of loss of glucagon counterregulation in type 1 diabetes mellitus and how best to manipulate glucagon to achieve more efficient and safer glycaemic control.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine and Center for Diabetes Technology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Leon S
authors.initials: LS
authors.lastname: Farhy
authors.forename: Anthony L
authors.initials: AL
authors.lastname: McCall
mesh_terms: D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005934:Glucagon / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000378:metabolism; D005943:Gluconeogenesis; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D010766:Phosphorylation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C493245:CRTC2 protein, human; D007328:Insulin; D014157:Transcription Factors; D005934:Glucagon; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051548:Histone Acetyltransferases