Role of transglutaminase in insulin release. Study with glycine and sarcosine methylesters.
The Ca2+-responsive enzyme transglutaminase, which catalyzes the cross-bridging of proteins, is present in pancreatic islet cells, but its participation in the process of insulin release remains to be documented. Glycine methylester (1.0-10.0 mM) inhibited, in a dose-related manner, transglutaminase activity in rat pancreatic islet homogenates, decreased [14C]methylamine incorporation into endogenous proteins of intact islets, and caused a rapid and reversible inhibition of insulin release evoked by D-glucose, while failing to affect D-[U-14C]glucose oxidation. Glycine methylester also inhibited insulin release induced by other nutrient or nonnutrient secretagogues. Sarcosine methylester failed to affect transglutaminase activity, [14C]methylamine incorporation, and insulin release. Both methylesters mobilized 45Ca from prelabeled intact islets, from membranes of islet cells, liver or brain, and from artificial lipid multilayers, this Ca mobilization being apparently unrelated to changes in transglutaminase activity. It is proposed that, in the pancreatic B cell, transglutaminase participates in the machinery controlling the access of secretory granules to the exocytotic sites.
Sener
A
A
Dunlop
M E
ME
Gomis
R
R
Mathias
P C
PC
Malaisse-Lagae
F
F
Malaisse
W J
WJ
D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002132:Calcium Radioisotopes / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D008744:Methylamines / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011503:Transglutaminases
D002132:Calcium Radioisotopes; D007328:Insulin; D008744:Methylamines; C038264:sarcosine methyl ester; C035591:glycine methyl ester; C027451:methylamine; D000217:Acyltransferases; D011503:Transglutaminases; D005947:Glucose; D002118:Calcium; D005998:Glycine; D012521:Sarcosine