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Inhibiting or antagonizing glucagon: making progress in diabetes care.

P J Lefèbvre1, N Paquot1, A J Scheen1,2

  • 1Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, University of Liège, Liège, Belgium.

Diabetes, Obesity & Metabolism
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Summary

Hyperglucagonaemia, or excess glucagon, is a key factor in diabetes. Targeting glucagon action or secretion offers innovative diabetes management strategies.

Keywords:
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Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Diabetes Research

Background:

  • Hyperglucagonaemia is a long-recognized feature of all diabetes types.
  • Excess glucagon secretion from islet alpha cells is linked to insulin defects.
  • Recent studies highlight glucagon's critical role in diabetes pathophysiology.

Purpose of the Study:

  • To explore the significance of hyperglucagonaemia in diabetes.
  • To evaluate targeting alpha cells and glucagon as innovative diabetes management approaches.
  • To review current and potential therapeutic strategies involving glucagon antagonism.

Main Methods:

  • Review of experimental and clinical studies on glucagon in diabetes.
  • Analysis of data from glucagon receptor knockout and antibody studies in diabetic rodents.
  • Examination of the mechanisms of existing diabetes drugs affecting glucagon.

Main Results:

  • Glucagon receptor blockade enables insulin-deficient diabetic rodents to thrive without insulin.
  • Several current diabetes medications partially inhibit glucagon secretion or action.
  • No selective glucagon antagonist is currently approved for diabetes treatment.

Conclusions:

  • Hyperglucagonaemia is a crucial, yet often overlooked, aspect of diabetes.
  • Targeting glucagon pathways presents a promising therapeutic avenue for diabetes management.
  • Careful consideration of potential risks, like hypoglycemia and liver injury, is essential in developing new glucagon-targeting therapies.