Glucose and carbachol activate phospholipase C in digitonin-permeabilized islets

Stimulation of intact islets with D-glucose, the major insulin secretagogue, or with carbachol, a muscarinic agonist, results in the accumulation of inositoltrisphosphate (IP3) suggesting that activation of phospholipase C (PLC) has a major role in stimulus-secretion coupling. Carbachol activation of PLC is an example of receptor-mediated activation in islets, whereas, the mechanism of glucose activation of PLC is controversial since a glucose receptor has not been identified. They have measured PLC activity in digitonin-permeabilized islets. Islets were labeled with 3H-inositol, permeabilized and IP3 accumulation measured by HPLC. Carbachol, in the presence of ATP, GTP and 1 μM free Ca2+ released two-fold more Ins 1,3,4-P3 than control in a time-dependent manner. Glucose, under the same conditions also significantly released more Ins 1,3,4-P3 than control. This effect was not due to metabolism of glucose nor to an effect on the IP3-phosphomonoesterase. Preliminary Ca2+-dependency studies indicate that PLC is not activated by Ca2+ in the submicromolar range. In conclusion, these studies show that Ca2+ does not activate PLC, and furthermore, that D-glucose may be recognized directly by PLC