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Glucagon Receptor Antagonism Improves Glucose Metabolism and Cardiac Function by Promoting AMP-Mediated Protein

Ankit X Sharma1, Ezekiel B Quittner-Strom1, Young Lee2

  • 1Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549, USA.

Cell Reports
|February 15, 2018
PubMed

Insights

Glucagon receptor antagonism improves blood sugar and insulin sensitivity in type 2 diabetes models. This treatment also protects against diabetic heart disease by reducing fat buildup and enhancing heart function.

Area of Science:

  • Metabolic diseases
  • Endocrinology
  • Cardiovascular research

Background:

  • Glucagon receptor antagonism is a potential therapeutic strategy for type 2 diabetes.
  • Hyperglucagonemia contributes to insulin resistance and diabetic complications.

Purpose of the Study:

  • To investigate the metabolic and cardiac effects of glucagon receptor antagonism in type 2 diabetes models.
  • To explore the role of hyperglucagonemia in insulin resistance and cardiac dysfunction.

Main Methods:

  • Treatment of Leprdb/db and Lepob/ob mice with REMD 2.59, a glucagon receptor antagonist antibody.
  • Assessment of glucose metabolism, insulin sensitivity, and cardiac function.
  • Analysis of AMP-activated protein kinase (AMPK)-mediated lipid oxidation.

Main Results:

  • REMD 2.59 suppressed hepatic glucose production and improved glycemia.
  • Enhanced insulin action in liver and skeletal muscle, with increased AMPK-mediated lipid oxidation.
  • Protection against diabetic cardiomyopathy and improved cardiac contractile function.

Conclusions:

  • Glucagon receptor antagonism offers a promising therapeutic approach for type 2 diabetes.
  • Hyperglucagonemia promotes lipotoxic conditions, leading to insulin resistance and cardiac dysfunction.
  • Targeting the glucagon receptor may ameliorate metabolic and cardiovascular complications in diabetes.
Keywords:
adiponectinceramidelipotoxicitysphingolipid

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