The use of calcium uptake by small amounts of mitochondria from pancreatic islets to study mitochondrial respiration: the effects of diazoxide and sodium.
The net uptake of 45Ca into mitochondria from pancreatic islets is stimulated by substrates that transfer reducing equivalents to various sites of the respiratory chain, such as succinate or glycerol 3-phosphate (site II), malate plus pyruvate (site I) or ascorbate plus TMPD (site III). Diazoxide, a known inhibitor of insulin release in vivo and in vitro, strongly inhibited net 45Ca uptake supported by glycerol phosphate and succinate and weakly inhibited 45Ca uptake supported by the other substrates. These results suggest that diazoxide, although not completely specific, is predominately an inhibitor at site II of the respiratory chain. This result is consistent with previous work that showed diazoxide inhibits the enzyme activity of the mitochondrial glycerol phosphate dehydrogenase in islets. Sodium ion inhibited the net accumulation of 45Ca by islet mitochondria suggesting a similarity between islet mitochondria and those of heart and some other endocrine tissues.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology*
D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D012964:Sodium; D003981:Diazoxide; D002118:Calcium