Glucagon deficiency reduces hepatic glucose production and improves glucose tolerance in adult mice

AS Hancock, A Du, J Liu, M Miller… - Molecular …, 2010 - academic.oup.com
AS Hancock, A Du, J Liu, M Miller, CL May
Molecular endocrinology, 2010academic.oup.com
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 …
Abstract
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.
Oxford University Press