T. Fridolf et B. Ahren, EFFECTS OF GLUCAGON-LIKE PEPTIDE-1(7-36) AMIDE ON THE CYTOPLASMIC CA-2-CONCENTRATION IN RAT ISLET CELLS(), Molecular and cellular endocrinology, 96(1-2), 1993, pp. 85-90
Glucagon like peptide-1(7-36)amide (GLP-1(7-36)amide) stimulates both
insulin secretion and the efflux of Ca-45(2+) from Ca-45(2+)-preloaded
rat islets in a Na+-dependent manner. This indicates that the peptide
stimulates insulin secretion by Na+-dependently increasing the intrac
ellular concentration of Ca2+ ([Ca2+]IC). However, whether GLP-1(7-36)
amide actually affects the [Ca2+]IC in islet cells is not known. We th
erefore preloaded rat islet cells with the Ca2+-fluorophor fura 2-AM a
nd examined the [Ca2+]IC in spectrophotofluorometry. We found that GLP
-1(7-36)amide increased [Ca2+]IC both at 3.3 and 8.3 mM glucose but on
ly in a medium containing both Ca2+ and Na+. Also the adenylate cyclas
e activator, forskolin (2.5 muM), increased the [Ca2+]IC but this acti
on was evidenced also in the absence of extracellular Na+. Furthermore
, the Ca2+-channel inhibitor, D-600 (50 muM), prevented the rise in [C
a2+]IC after both forskolin and GLP-1(7-36)amide, whereas pertussis to
xin had no effect. The results show that GLP-1(7-36)amide increases th
e [Ca2+]IC in islets cells by an action that most likely is due to upt
ake of extracellular Ca2+ by a Na+-dependent mechanism, whereas forsko
lin increases [Ca2+]IC independently on Na+. It is hypothesized that G
LP-1(7-36)amide stimulates a Na+-dependent step prior to the catalytic
unit of the adenylate cyclase complex in islet cells.