Lithium's effects on rat liver glucose metabolism in vivo.
Oral administration of lithium carbonate to fed-healthy rats strongly decreased liver glycogen content, despite the simultaneous activation of glycogen synthase and the inactivation of glycogen phosphorylase. The effect seemed to be related to a decrease in glucose 6-phosphate concentration and to a decrease in glucokinase activity. Moreover, in these animals lithium markedly decreased liver fructose 2,6-bisphosphate, which could be a consequence of the fall in glucose 6-phosphate and of the inactivation of 6-phosphofructo-2-kinase. Liver pyruvate kinase activity and blood insulin also decreased after lithium administration. Lower doses of lithium carbonate had less intense effects. Lithium administration to starved-healthy and fed-streptozotocin-diabetic rats caused a slight increase in blood insulin, which was simultaneous with increases in liver glycogen, glucose 6-phosphate, and fructose 2, 6-phosphate. Glucokinase, 6-phosphofructo-2-kinase, and pyruvate kinase activities also increased after lithium administration in starved-healthy and fed-diabetic rats. Lithium treatment activated glycogen synthase and inactivated glycogen phosphorylase in a manner similar to that observed in fed-healthy rats. Glycemia was not modified in any group of animals. These results indicate that lithium acts on liver glycogen metabolism in vivo in at least two different ways: one related to changes in insulinemia, and the other related to the direct action of lithium on the activity of some key enzymes of liver glucose metabolism.
Rodriguez-Gil
J E
JE
Unit of Reproduction, Autonomous University of Barcelona, Bellaterra, E-08193, Spain.
Fernández-Novell
J M
JM
Barberá
A
A
Guinovart
J J
JJ
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005508:Food Deprivation; D005635:Fructosediphosphates / Q000378:metabolism; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000032:analysis / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000097:blood; D016651:Lithium Carbonate / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D008112:Liver Glycogen / Q000032:analysis / Q000378:metabolism; D008297:Male; D025481:Phosphofructokinase-2; D006005:Phosphorylases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
D005635:Fructosediphosphates; D007328:Insulin; D008112:Liver Glycogen; D016651:Lithium Carbonate; D019298:Glucose-6-Phosphate; C027652:fructose 2,6-diphosphate; D006005:Phosphorylases; D006006:Glycogen Synthase; D017853:Phosphotransferases (Alcohol Group Acceptor); D025481:Phosphofructokinase-2; D005941:Glucokinase; D011770:Pyruvate Kinase; D005947:Glucose