|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1996 : ¥1,400,000 (Direct Cost : ¥1,400,000)
In pancreatic B cells isolated from normal adult and normal young rats, the intracellular free Ca^<2+> concentration ([Ca^<2+>]i) and the membrane potential were measured by fluorescent microscopy using fura 2 and patch clamp technique, respectively. Furthermore, the possibility that denervation of the sympathetic nervous system affects responsiveness of B cells to drugs was examined.
In the presence of partially stimulating concentrations of glucose or tolbutamide, agents that facilitate NO production or augment intracellular cyclic GMP content, such as 8-bromo-cyclic GMP,human atrial natriuretic peptide, L-arginine, sodium nitroprusside, NOC 5 and NOC 7, increased [Ca^<2+>]i of B cells isolated from normal adult rats, as observed with cyclic AMP.However, these agents failed to increase [Ca^<2+>]i of B cells when tested under depolarization of the plasma membrane with high concentrations of K^+. The increase in [Ca^<2+>]i was considered to be mainly due to Ca^<2+> influx through the plasma membrane. In the case of B cells isolated from normal young or sympathectomized adult rats, effects of the NO-cyclic GMP-related agents were similar to those observed with B cells isolated from normal adult rats.
These results suggest that activation of the NO-cyclic GMP system positively medullates the release of insulin from pancreatic B cells under the physiological conditions. Possible changes in the B cell function during aging need to be elucidated.