Glucagon deficiency reduces hepatic glucose production and improves glucose tolerance in adult mice.
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 alpha-cell transcription factor, Arx, resulting in a complete loss of the glucagon-producing pancreatic alpha-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.
Hancock
Aidan S
AS
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Du
Aiping
A
Liu
Jingxuan
J
Miller
Mayumi
M
May
Catherine L
CL
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D005934:Glucagon / Q000172:deficiency / Q000502:physiology*; D050416:Glucagon-Secreting Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000166:cytology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D050418:Pancreatic Polypeptide-Secreting Cells / Q000166:cytology; D016133:Polymerase Chain Reaction; D019864:Somatostatin-Secreting Cells / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
C469265:ARX protein, mouse; D001786:Blood Glucose; D018398:Homeodomain Proteins; D014157:Transcription Factors; D005934:Glucagon