Dynamics of insulin and cyclic adenosine 3',5'-monophosphate release from the perifused rat islets of langerhans under a slow-rise stimulation with D-glucose and its anomers.

Abstract

Insulin and cyclic adenosine 3', 5'-monophosphate (cAMP) release from the perifused islets was examined under a slow-rise stimulation by D-glucose, D-galactose and the anomers of D-glucose, using a technique of the double chamber method.The insulin and cAMP secretory responses of the B cell to D-glucose showed sigmoidal curves with Km of 6.6±1.0mM glucose for insulin release and with Km of 6.0±0.7mM glucose for cAMP release. The respective Km values of α-and β-D-glucose were 4.5±0.3 and 5.9±0.2mM for insulin release, and 4.0±0.6 and 5.3±0.9mM for cAMP release. The thresholds for insulin and cAMP release due to the α anomer were 4.0and 3.0mM glucose, respectively, while the respective thresholds of the β anomer were 4.6 and 4.0mM for insulin and cAMP release, the former being more potent than the latter in stimulating insulin and cAMP release. Furthermore, it seems obvious that the release of cAMP slightly precedes insulin release at low concentrations under a slow-rise stimulation with the anomers. These results suggest that cAMP may be released not only from the B granules by exocytosis but also from another compartment located in the cell membrane or near the membrane. Hill plots for the rates of cAMP and insulin release were represented as straight lines but Lineweaver-Burks plots were parabolic functions in all cases.Consequently, these data suggest that the pancreatic B cell may contain glucoreceptors and the binding of the glucose molecules to the receptors may directly cause the activation of the adenylate cyclase, which, in turn, leads to the accumulation of cAMP in islets and perifusion medium.