Facilitation of insulin release by N-p-tosylglycine.
N-p-tosylglycine, which inhibits transglutaminase activity in islet homogenates, was found to cause a rapid and sustained facilitation of insulin release evoked by D-glucose, L-leucine or the association of Ba2+ and theophylline in intact islets. Such a facilitating action could not be attributed to any obvious effect upon either nutrient oxidation or 45Ca net uptake and outflow. It failed to be reproduced by glycine, N alpha-p-tosyl-L-arginine methyl ester or N alpha-p-tosyl-L-lysine methyl ester. N-p-tosylglycine (5.0 mM) slightly enhanced insulin release evoked by a high concentration of glucose (16.7 mM) and failed to affect significantly the secretory response to the association of L-leucine and L-glutamine or that of D-glucose and gliclazide. N-p-tosylglycine failed to affect the incorporation of [2,5-3H]histamine in trichloroacetic acid-precipitable material in intact islets. These results suggest that N-p-tosylglycine interferes with a late event in the secretory sequence, possibly at the level of the cell boundary, rather than inhibiting the crosslinking of intracellular proteins.
Sener
A
A
Gomis
R
R
Billaudel
B
B
Malaisse
W J
WJ
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects; D051381:Rats; D013806:Theophylline / Q000494:pharmacology; D011503:Transglutaminases
D007328:Insulin; C045910:N-4-tosylglycine; D001464:Barium; D013806:Theophylline; D000217:Acyltransferases; D011503:Transglutaminases; D005947:Glucose; D002118:Calcium; D005998:Glycine