Ultrastructural changes produced by glucagon, cyclic 3′5′-AMP and epinephrine on perfused rat livers

Rosa, Francisco

doi:10.1016/s0022-5320(71)80068-0

Cited by 51 publications

(23 citation statements)

References 20 publications

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“…It has also been reported that the peroxisomes are incorporated along with other cellular materials into double-membrane-limited bodies resembling autolysosomes during the long-term administration of CPIB or after its withdrawal (Svoboda et al, 1967)) . The formation of autophagolysosomes has been observed in the hepatic parencymal cells of the rat following glucagon administration (Ashford and Porter, 1962;Deter and de Duve, 1967;Rosa, 1971;) and the present study showed that the autophagolysosome formation takes place even in the CPIB-treated and glucagon-administered rat liver. These findings clearly indicate the participation of lysosomes in the autophagy of peroxisomes induced by CPIB.…”

Section: Fig I Hepatic Parenchymalsupporting

confidence: 66%

Autophagy of peroxisomes in hepatic parenchymal cells.

Matsushita

Saito

Keino

et al. 1982

Acta Histochem. Cytochem

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Section: Fig I Hepatic Parenchymalsupporting

confidence: 66%

Autophagy of peroxisomes in hepatic parenchymal cells.

Matsushita

Saito

Keino

et al. 1982

Acta Histochem. Cytochem

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“…Previous studies have indicated that cAMP stimulates hepatocytic autophagy in vivo [17,181, in perfused livers [16,381 and in hepatocyte cultures [14,151. In freshly isolated hepatocytes, autophagy may be stimulated, inhibited or unaffected by CAMP, depending on the ambient metabolic conditions [19,391.…”

Section: Discussionmentioning

confidence: 99%

“…A large number of reports have been published concerning the effects of CAMP on various hepatocytic processes, including protein degradation. Agents that elevate the level of intracellular CAMP have been shown to stimulate protein degradation in hepatocyte monolayers [14,151, in the perfused liver [16] and in vivo [17, 181. In isolated hepatocytes in suspension, the CAMP-elevating hormone glucagon was found to stimulate, inhibit or have no effect on autophagy, depending on the metabolic environment [ 191. The present study was undertaken to further investigate how the CAMP-signaling pathway may be involved in the control of autophagy in freshly isolated hepatocytes, by use of various cAMP analogues, and through elevating or decreasing the endogenous cAMP levels.…”

mentioning

confidence: 99%

Role of cAMP in the Regulation of Hepatocytic Autophagy

Holen

Gordon

Strømhaug

et al. 1996

European Journal of Biochemistry

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To assess the role of CAMP in the regulation of autophagy, we examined the effects of CAMP analogues and CAMP-elevating agents on freshly isolated rat hepatocytes, using electroinjected ['Hlraffinose as an autophagy probe. Glucagon was found to stimulate, inhibit or have no effect on autophagy, depending on the inclusion of metabolites like pyruvate (which caused ATP depletion and autophagy suppression) and amino acids (a complete mixture that antagonized pyruvate) in the incubation medium. Inhibition was also observed with theophylline, a CAMP-elevating inhibitor of cyclic nucleotide phosphodiesterases, and with the adenylyl cyclase activator deacetylforskolin. At low concentrations of deacetylforskolin, the inhibition could be abolished by amino acids. N6,2'-O-Dibutyryladenosine 3',S'-monophosphate (Bt,-CAMP) strongly inhibited both autophagic sequestration of ['Hlraffinose and overall autophagic protein degradation ; again, amino acids abolished the autophagy-inhibitory effect of low Bt,-CAMP concentrations. Several other CAMP analogues { 8-thiomethyl-CAMP, Nb-benzoyl-CAMP, (S)-S,6-dichloro-l-D-ribofuranosylbenzimidazole 3',S'-[thio]monophosphate, (S)-8-bromoadenosine 3',S'-[thio]monophosphate} inhibited autophagy as well. The effect of Bt,-CAMP was rapid, dose-dependent, reversible and did not require concomitant protein synthesis. Neither Bt,-CAMP nor deacetylforskolin reduced intracellular ATP levels or cell viability, ruling out inhibition of autophagy by non-specific cytotoxicity. The autophagy-inhibitory effect of Bt,-CAMP could be substantially antagonized (40-SO %) by KT-5720, a specific inhibitor of the CAMP-dependent protein kinase A, and by the nonspecific protein kinase inhibitor K-2S2a. Somewhat surprisingly, KN-62 and KT-5926, allegedly specific inhibitors of Ca2+/calmodulindependent protein kinase I1 and myosin light chain kinase, respectively, were also Bt,-CAMP-antagonistic. These results suggest that CAMP regulates the early, sequestrational step of hepatocytic autophagy by a highly conditional, dual mechanism, inhibition being predominant under most conditions in freshly isolated hepatocytes, whereas stimulation reportedly predominates in vivo. The effect of CAMP is probably mediated by protein kinase A, but other protein kinases would appear to participate in the regulation of autophagic sequestration as well.

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“…The third suggestive line of evidence is the hypoaminoacidemic effect of exogenous glucagon in the fetus' as well as the adult (10,12). Fourth, the glucagon induction of autophagocytosis due to increased lysosomal activity has been shown in the adult rat liver (52), and such changes occur spontaneously after birth (53). Fifth, a marked increase in liver 3',5'-cyclic AMP has been demonstrated after birth, which would be expected with increased endogenous glucagon, particularly if associated with decrease in the insulin/glucagon ratio (53,54).…”

Section: Methodsmentioning

confidence: 97%

Fuels, Hormones, and Liver Metabolism at Term and during the Early Postnatal Period in the Rat

Girard¹,

Cuendet²,

Marliss³

et al. 1973

J. Clin. Invest.

372

238

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A B ST R A C T The metabolic response to the first fast experienced by all mammals has been studied in the newborn rat. Levels of fuels and hormones have been compared in the fetal and maternal circulations at term. Then, after cesarean section just before the normal time of birth, sequential changes in the same parameters were quantified during the first 16 h of the neonatal period. No caloric intake was permitted, and the newborns were maintained at 370C. Activities of three key hepatic enzymes involved in glucose production were estimated.Marked differences in maternal and fetal hormones and fuels were observed. Lower levels of glucose, free fatty acids, and glycerol but higher levels of lactate, a-amino nitrogen, alanine, and glutamine were present in the fetus. Pyruvate, glutamate, and ketone bodies were not significantly different. The combination of a strikingly higher fetal immunoreactive insulin and a slightly lower immunoreactive glucagon (pancreatic) resulted in a profound elevation in the insulin-to-glucagon ratio, a finding consistent with an organism in an anabolic state.The rat at birth presents a body composition with respect to fuels available for mobilization and conversion which is dominated by carbohydrate and protein, since little fat is present. However, at birth a transient period of hypoglycemia occurred, associated with a rapid fall in insulin and rise in glucagon, causing reversal of the insulin-to-glucagon relationship toward ratios such as were observed in the mother. After a lag period, hepatic activities of phosphorylase, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase increased. Concurrent with these enzyme changes, the blood glucose returned to levels at or above those of the fetus. Interestingly, the fall observed in levels of the gluconeogenic precursors, lactate and amino acids, preceded the rise in enzyme activities and restoration of blood glucose. After 4 h, however, hypoglycemia recurred, during a period of decreasing hepatic glycogen content and blood lactate, pyruvate, and glycerol levels but of stable or increasing amino acid concentrations. Hepatic gluconeogenesis in this phase of depleted glycogen stores was insufficient to maintain euglycemia.Substrates derived from fat showed early changes of smaller magnitude. The rise in free fatty acids which occurred was less than twofold the value at birth, though this rise persisted up to 6 h. Whereas glycerol rose transiently, acetoacetate did not change and P-hydroxybutyrate concentration fell. Both ketone bodies showed a marked rise at 16 h, at a time of diminished free fatty acid levels. Plasma growth hormone, though higher in the fetal than the maternal circulation, showed no consistent change during the period of observation.The changes in levels of the endocrine pancreatic hormones at birth were appropriate in time, magnitude, and direction to be implicated as prime regulators of the metabolic response during the neonatal period in the rat.

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Ultrastructural changes produced by glucagon, cyclic 3′5′-AMP and epinephrine on perfused rat livers

Cited by 51 publications

References 20 publications

Autophagy of peroxisomes in hepatic parenchymal cells.

Autophagy of peroxisomes in hepatic parenchymal cells.

Role of cAMP in the Regulation of Hepatocytic Autophagy

Fuels, Hormones, and Liver Metabolism at Term and during the Early Postnatal Period in the Rat

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