Effects of actinomycin D on dexamethasone induced hepatic glycogen accumulation: morphological and biochemical observations.
Effects of inhibition of protein synthesis by actinomycin D (ACT) on the acute stimulation of hepatic gluconeogenesis and glucose-6-phosphatase (G6Pase) by the glucocorticoid, dexamethasone (DEX), in adrenalectomized (ADX) rats, were investigated using both morphological and biochemical means. Examination of ultra-thin sections of liver in the electron microscope revealed that ACT, administered alone or with DEX, resulted in a failure of hepatic glycogen accumulation to occur. Smooth endoplasmic reticulum (SER) appeared similar to that of the ADX-untreated animals, with occasional suggestions of increased amounts of membrane in ACT-treated animals. G6Pase activity in homogenates was increased, as was activation of the enzyme under all experimental conditions, when compared with ADX-untreated controls. The DEX-induced increase in G6Pase activity in SER failed to occur to any appreciable extent in ACT-treated animals. Plasma glucose levels increased slightly when ACT and DEX were present simultaneously. It is suggested that ACT countered the inductive effects of DEX on hepatic glycogen synthesis, but only partially suppressed acute stimulation of gluconeogenesis. A possible superinduction of G6Pase enzyme synthesis through increased efficiency of translation of extant mRNA is discussed. It is proposed that ACT inhibited the formation of appropriate SER membranes and/or other components necessary for glycogen accumulation.
D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004247:DNA / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006651:Histocytochemistry; D007328:Insulin / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D011506:Proteins / Q000378:metabolism; D051381:Rats
D001786:Blood Glucose; D007328:Insulin; D008112:Liver Glycogen; D011506:Proteins; D003609:Dactinomycin; D003907:Dexamethasone; D004247:DNA; D005952:Glucose-6-Phosphatase