Progressive Loss of Sensitivity of the A Cell to Insulin in Geese Made Diabetic by Subtotal Pancreatectomy

Summary

The effects of insulin deficiency on pancreatic A cell responsiveness to glucose was studied in subtotally depancreatized geese.

In geese operated for 3 to 5 days and receiving insulin therapy (I.M.: 0.5-1.0 U/kg/24 h), A cell response to glucose (I.V. injection: 0.5 g/kg was abolished, but could be restored to normal range by insulin (I.V. injection: 0.025-0.2 U/kg) together with glucose. After 5 weeks of therapy, A cell sensitivity declined: the physiological amount of insulin (0.025 U/kg) was insufficient to suppress glucagon during the glucose load, whereas the large dose (0.2 U/kg) partially restored A cell response. In addition, daily insulin treatment prevented a severe increase of fasting plasma glucose and glucagon.

Geese receiving no insulin therapy showed “total blindness” to glucose, even when given insulin at the time of the test. These data suggest a progressive loss of sensitivity of the A cell to insulin. Endocrine and/or paracrine insulin deficiency may play a role on the dysfunction of the glucose-glucagon feedback mechanism.

Key-Words:

Glucose - Insulin - Glucagon - Glucose Tolerance Test - Insulin Therapy - A Cell - Subtotal Pancreatectomy - Geese