Glucagon Deficiency Reduces Hepatic Glucose Production and Improves Glucose Tolerance In Adult Mice

• Published in: Molecular endocrinology (Baltimore, Md.) Md.), 2010-08, Vol.24 (8), p.1605-1614
• Main Authors: Hancock, Aidan S, Du, Aiping, Liu, Jingxuan, Miller, Mayumi, May, Catherine L
• Format: Article
• Language: English
• Subjects: Animals; Blood Glucose - metabolism; Blotting, Western; Glucagon - deficiency; Glucagon - physiology; Glucagon-Secreting Cells - cytology; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; Insulin-Secreting Cells - cytology; Male; Mice; Mice, Mutant Strains; Pancreatic Polypeptide-Secreting Cells - cytology; Polymerase Chain Reaction; Somatostatin-Secreting Cells - cytology; Transcription Factors - genetics; Transcription Factors - physiology
• ISSN: 0888-8809; 1944-9917
• DOI: 10.1210/me.2010-0120

The major role of glucagon is to promote hepatic gluconeogenesis and glycogenolysis to raise blood glucose levels during hypoglycemic conditions. Several animal models have been established to examine the in vivo function of glucagon in the liver through attenuation of glucagon via glucagon receptor knockout animals and pharmacological interventions. To investigate the consequences of glucagon loss to hepatic glucose production and glucose homeostasis, we derived mice with a pancreas specific ablation of the α-cell transcription factor, Arx, resulting in a complete loss of the glucagon-producing pancreatic α-cell. Using this model, we found that glucagon is not required for the general health of mice but is essential for total hepatic glucose production. Our data clarifies the importance of glucagon during the regulation of fasting and postprandial glucose homeostasis. Glucagon is not required for general health, but is essential for hepatic glucose production and regulation of glucose homeostasis.