Reversal of Glucose-Induced Inhibition of Insulin Release by Dibutyryl Cyclic AMP

Summary

Insulin release in response to glucose was measured after culture of islets from ob/obmice in a medium deficient in Ca²⁺. When present at a concentration of 6 mmol/1, glucose inhibited, insulin release. After activation of the <α₂-adrenergic receptors by 1 µmol/1 clonidine also 20 mmol/1 glucose became inhibitory. The inhibitory action of glucose oa insulin release disappeared in the presence of 1 mmol/1 dibutyryl cyclic AMP. Raising the glucose concentration from 3 to 20 mmol/1 resulted in increased cytoplasmic Ca²⁺ after an initial depression. Whereas clonidine removed the Ca²⁺ increase, this phase was partly restored after simultaneous addition of dibutyryl cyclic AMP. It is concluded that cyclic AMP plays a major role in controlling the balance between the stimulatory and inhibitory components in the glucose action on insulin release.

Key Words

Pancreatic islets - Insulin release - Glucose inhibition - Cytoplasmic Ca²⁺ - Cyclic AMP