Reversal of glucose-induced inhibition of insulin release by dibutyryl cyclic AMP.
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/l, glucose inhibited, insulin release. After activation of the alpha2-adrenergic receptors by 1 mumol/l clonidine also 20 mmol/l glucose became inhibitory. The inhibitory action of glucose on insulin release disappeared in the presence of 1 mmol/l dibutyryl cyclic AMP. Raising the glucose concentration from 3 to 20 mmol/l 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.
Bergsten
P
P
Department of Medical Cell Biology, University of Uppsala, Sweden.
Löfberg
C
C
Hellman
B
B
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D003593:Cytoplasm / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese
D007328:Insulin; D003994:Bucladesine; D005947:Glucose; D003000:Clonidine; D002118:Calcium