Changes in IP3 receptor are associated with altered calcium response to cholecystokinin in diabetic rat pancreatic acini.
OBJECTIVE
Pancreatic acini of diabetic rats release amylase less than normal acini on cholecystokinin (CCK) stimulation. Pancreatic enzyme secretion by CCK is closely related to the second messenger inositol 1,4,5-trisphosphate (IP3), which mobilizes intracellular calcium stores via the endoplasmic reticulum-located receptor IP3 (IP3R). Recently, we observed altered intracellular calcium response on CCK-8 stimulation in streptozotocin (STZ)- treated diabetic rat acini.


METHODS
To determine whether IP3R is involved in altered calcium response, we measured inositol phosphate (IP) formation and the expression and phosphorylation of type III IP3R protein in diabetic acini. Also, CCK receptor mRNA expression was examined to determine whether the changes in IP formation and IP3R protein phosphorylation in diabetic acini might result from the defect at the postreceptor level.


RESULTS
CCK-8-induced IP formation at all concentrations used was significantly reduced in diabetic acini, though IP formation was increased in a concentration-dependent manner. The expression of type III IP3R protein was significantly reduced in diabetic acini. Additionally, CCK-8-stimulated phosphorylation of type III IP3R protein was not observed in diabetic acini. However, the reduction of CCK receptor mRNA expression was not detected in diabetic acini.


CONCLUSIONS
Our results indicate that altered calcium response to CCK-8 in diabetic acini might be associated with a post-CCK receptor defect including the changes in IP formation, type III IP3R protein expression, and phosphorylation of type III IP3R protein.
Ryu
Gyeong Ryul
GR
Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Sung
Choon Ho
CH
Kim
Myung-Jun
MJ
Sung
Jong-Ho
JH
Lee
Kweon-Haeng
KH
Park
Dong Won
DW
Sim
Sang Soo
SS
Min
Do Sik
DS
Rhie
Duck-Joo
DJ
Yoon
Shin Hee
SH
Hahn
Sang June
SJ
Kim
Myung-Suk
MS
Jo
And Yang-Hyeok
AY
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002766:Cholecystokinin / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012844:Sincalide / Q000378:metabolism*; D013311:Streptozocin; D014316:Tritium / Q000378:metabolism
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; D018160:Receptors, Cytoplasmic and Nuclear; D014316:Tritium; D013311:Streptozocin; D002766:Cholecystokinin; D012844:Sincalide; D002118:Calcium