Effects of thioacetamide on pancreatic islet B-cell function.
Thioacetamide (0.01-1.3 mM) fails to exert any significant immediate effect upon insulin release from rat isolated islets. However, when administered (4 micromol/g body wt) intraperitoneally 24 h before sacrifice, it reduced food intake and body weight and affected the secretory response of isolated islets to several secretagogues, despite unaltered insulin content of such islets. This coincided with a decrease in D-[U-14C]glucose oxidation, total islet calcium content and the ionized calcium content of secretory granules in islet B-cells, and changes in both 133Ba and 45Ca net uptake. Likewise, in islets prepared from thioacetamide-injected rats and prelabeled with 45Ca before perifusion, the cationic and insulin secretory responses to D-glucose or gliclazide, but not to the association of Ba2+ and theophylline in the absence of extracellular Ca2+, often differed from that otherwise found in islets prepared from control rats. These findings are interpreted as indicative of an impaired capacity of Ca2+ sequestration by intracellular organelles in the islet B-cells of thioacetamide-treated rats.
Malaisse
Willy J
WJ
Laboratories of Experimental Hormonology and Pharmacology, Brussels Free University, Brussels, Belgium. malaisse@ulb.ac.be
Lebrun
Philippe
P
Sener
Abdullah
A
Wolters
Gerrit H J
GH
Ravazzola
Mariella
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D010477:Perfusion; D011868:Radioisotopes; D051381:Rats; D013853:Thioacetamide / Q000494:pharmacology*
D007328:Insulin; D011868:Radioisotopes; D013853:Thioacetamide; D005947:Glucose; D002118:Calcium