Current Diabetes Reports

, 14:555 | Cite as

Glucagon and Type 2 Diabetes: the Return of the Alpha Cell

  • Asger Lund
  • Jonatan I. Bagger
  • Mikkel Christensen
  • Filip K. Knop
  • Tina Vilsbøll
Pathogenesis of Type 2 Diabetes and Insulin Resistance (RM Watanabe, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Pathogenesis of Type 2 Diabetes and Insulin Resistance


In normal physiology, glucagon from pancreatic alpha cells plays an important role in maintaining glucose homeostasis via its regulatory effect on hepatic glucose production. Patients with type 2 diabetes suffer from fasting and postprandial hyperglucagonemia, which stimulate hepatic glucose production and, thus, contribute to the hyperglycemia characterizing these patients. Although this has been known for years, research focusing on alpha cell (patho)physiology has historically been dwarfed by research on beta cells and insulin. Today the mechanisms behind type 2 diabetic hyperglucagonemia are still poorly understood. Preclinical and clinical studies have shown that the gastrointestinal hormone glucose-dependent insulinotropic polypeptide (GIP) might play an important role in this pathophysiological phenomenon. Furthermore, it has become apparent that suppression of glucagon secretion or antagonization of the glucagon receptor constitutes potentially effective treatment strategies for patients with type 2 diabetes. In this review, we focus on the regulation of glucagon secretion by the incretin hormones glucagon-like peptide-1 (GLP-1) and GIP. Furthermore, potential advantages and limitations of suppressing glucagon secretion or antagonizing the glucagon receptor, respectively, in the treatment of patients with type 2 diabetes will be discussed.


Alpha cell Glucagon GIP GLP-1 Type 2 diabetes 


Author Contribution

All authors contributed substantially to the conception of the work, drafting of the manuscript, and/or revising it critically for important intellectual content. Also, all authors gave final approval of the version to be submitted and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Compliance with Ethics Guidelines

Conflict of Interest

Asger Lund, Jonatan I. Bagger, and Mikkel Christensen declare that they have no conflict of interest.

Filip K. Knop has received research support through grants from the Novo Nordisk Foundation, the European Foundation for the Study of Diabetes (EFSD), and Sanofi-Aventis; has received lecture fees from AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly and Company, Gilead Sciences, Merck Sharp & Dohme, Novo Nordisk, Ono Pharmaceuticals, Sanofi, and Zealand Pharma; is a member of the Advisory Boards of Eli Lilly, Bristol-Myers Squibb/AstraZeneca, and Zealand Pharma; and has consulted for AstraZeneca, Gilead Sciences, Novo Nordisk, Ono Pharmaceuticals and Zealand Pharma.

Tina Vilsbøll has received lecture fees from AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly and Company, Merck Sharp & Dohme, Novo Nordisk, Novartis, Sanofi, and Zealand Pharma and is a member of the Advisory Boards of Eli Lilly, Novo Nordisk, GI-dynamics, Merck Sharp & Dohme, Takeda and Bristol-Myers Squibb/AstraZeneca.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Asger Lund
    • 1
    • 2
  • Jonatan I. Bagger
    • 1
    • 2
  • Mikkel Christensen
    • 1
    • 2
    • 3
  • Filip K. Knop
    • 1
    • 2
  • Tina Vilsbøll
    • 1
  1. 1.Center for Diabetes Research, Department of Medicine, Gentofte HospitalUniversity of CopenhagenHellerupDenmark
  2. 2.Department of Biomedical Sciences, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  3. 3.Department of Clinical Pharmacology, Bispebjerg HospitalUniversity of CopenhagenCopenhagenDenmark

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