The binding of insulin (IMS) and glucagon (GL) on isolated rat hepatocytes during the process of liver regeneration after partial hepatectomy was determined. Adult male rats were subjected to 65-70 % partial hepatectomy, control animals were sham-operated. The binding of radioiodine labelled IMS and GL to isolated hepatocytes was determined 1, 2, 3 and 5 days after the surgery. The plasma levels of IMS and glucose and microviscosity of liver plasma membranes were also measured. The decrease of IMS receptor binding capacity was found 1, 2, and 3 days after operation. Mo differences in sham and partially hepatectomized groups in IMS binding were noted 5 days after operation. A single insulin injection during the process of regeneration did not affect these changes of IMS binding to hepatocytes. The increase of GL binding was observed on the third day after partial hepatectomy, however, on the 5th day no changes of GL binding to its receptors were noted. The plasma insulin and glucose levels were similar in both hepatectomized and sham-operated rats. The increase of plasma membrane microviscosity of hepatocytes during the process of liver regeneration and a negative correlation between IMS binding and membrane microviscosity were found. These results demonstrated significant changes in binding parameters of both IMS and GL receptors in hepatocytes during liver regeneration induced by partial hepatectomy.
Glucagon and α-adrenergic-induced glycog enolysis is realized via the agonist/adenylyl cyclase/cAMP/protein kinase signaling pathway or via the activation of phosphorylase kinase by the mobilized calcium that supports the inhibition of glycogen synthase, respectively. The role of nitric oxide (NO) in this process has not been extensively studied. The present work was directed to the question whether NO is produced during glucagon-induced glycogenolysis in rat hepatocyte in a similar way like α-adrenoceptor stimulation. Glycogen-rich hepatocyte cultures were used. NO production (NO2-) was assessed under the influence of glucagon, dibutyryl cyclic AMP (db-cAMP), forskolin, the nitric oxide synthase (NOS) inhibitors Nω-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, and the NO donor S-nitroso-N-acetyl penicillamine (SNAP). Inducible NOS (iNOS) mRNA was examined by reverse transcription-polymerase chain reaction. Glycogenolysis was followed up by estimation of medium glucose levels. The amount of glucose and NO2- released by glycogen-rich hepatocytes was increased as a result of glucagon, db-cAMP, forskolin and SNAP treatments. iNOS gene expression was upregulated by glucagon. Glycogenolysis that occurs through glucagon receptor stimulation involves NO production downstream of transduction pathways through an isoform of NO synthase. The present and previous studies document possible involvement of NO signaling in glycogenolytic response to glucagon and adrenergic agonists in hepatocytes., H. Farghali, J. Hodis, N. Kutinová-Canová, P. Potměšil, E. Kmoníčková, Z. Zídek., and Obsahuje bibliografii a bibliografické odkazy
We measured hormonal levels in blood samples from pulmonary and radial arteries in 117 patients undergoing aorto-coronary by-pass surgery with the aim of investigating the role of the pulmonary vessel endothelium in hormone metabolism. Insulin and glucagon concentrations were significantly higher in pulmonary artery blood with respect to radial artery blood (73±65 vs. 65±47 pmol/l, p<0.005, and 80+49 vs. 73+51 ng/l, p<0.01, respectively), while no difference was found for growth hormone, prolactin, C peptide, insulin-like growth factor I, follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone, parathyroid hormone, thyroglobulin, triiodothyronine, thyroxine, free triiodothyronine, and free thyroxine. Moreover, prolactin concentrations were more than twice the normal levels, this being an effect of propafol and the opiate fentanyl used for the general anesthesia. Assuming that the arteriovenous differences observed are a marker of peptide hormone degradation, our study has demonstrated that with similar kinetics insulin and glucagon secreted into portal circulation and escaping from hepatic extraction undergo further homeostatic removal of about 9-10 % in the pulmonary circulation before entering the general circulation., G. Aliberti, I. Pulignano, M. Proietta, F. Miraldi, L. Cigognetti, L. Tritapepe, C. Di Giovanni, R. Arzilla, E. Vecci, M. Toscano., and Obsahuje bibliografii
Effects of early neonatal interventions on metabolic parameters later in life (s.c. late effects) were studied in rats using two models; namely, (a) the effects of premature weaning and (b) the effects of "dietary" manipulations during the suckling period (s.c. small vs. large litters), (a) Premature weaning of rats caused an earlier degeneration of spermiogenesis and elevated plasma cholesterol levels in adult animals when compared to levels found in animals weaned 12 days later (on day 30 after birth). In adult rats, radioiodine uptake in thyroid glands was lower in the group weaned prematurely. Premature weaning was followed by a decrease of corticosterone production in adrenal glands in adult animals; in female adult prematurely weaned rats, an elevated response of adrenal cortex to stressors was observed. Several other studies explored the "immediate" effects of early, premature weaning, (b) Early exposure to high fat diet evoked a hypercholesterolaemic response in adulthood following brief exposure to HF diet. Rats from litters reduced to 3 or 4 pups per mother on postnatal day 3 exhibited 2 days later plasma levels of cholesterol higher than in rats raised in large litters of 8 or 14. The difference between small and large litters was preserved for the whole lifespan of the animals. In adulthood, rats from small litters were fatter and had higher levels of plasma cholesterol and insulin. Other studies suggester that early dietary experience may regulate the pattern of drug metabolism in adult life. An inhibition of diurnal plasma corticosterone variation was found in rats overfed during the neonatal period and an increased stimulation of lipolysis by norepinephrine and lipogenesis by insulin was demonstrated in neonatally underfed rats. Interesting studies were reported in longitudinally studies in children: at the age of 9-12 year brest-fed children (for more than 6 months) had the highest cholesterol levels; on the other hand significantly increased levels of APO B, Apo Al, ATH index and Apo/B Apo A1 quotient (p<0.05) were found in the nonbreast-fed group (27 references).
We evaluated the effect of glucagon on cardiac automaticity as well as the possible role of cyclic nucleotide phosphodiesterases (PDE) in regulating this effect. Concentration response curves for glucagon in the absence and in th e presence of the non-selective PDE inhibitor IBMX were performed in the isolated right ventricle of the rat. We found that glucagon produces only a minor increase of ventricular automa ticity (11.0±4.1, n=5) when compared to the full agonist of β-adrenoceptor isoproterenol (182.2±25.3, n=7). However, IBMX enhances the maximal efficacy of glucagon on cardiac automaticity (11.0±4.1, in the absence and 45.3±3.2 in the presence of IBMX, n=5, P<0.05). These results indicate that PDE blunts proarrhythmic effects of glucagon in rat myocardium., C. Gonzalez-Muñoz, J. Hernández., and Obsahuje bibliografii a bibliografické odkazy
Infant rats received an i. p. injection of insulin, anti-insulin serum, streptozotocin, antiglucagon serum or dexamethazone. All substances except the antiinsulin serum, raised the plasma triglyceride level. Both antisera decreased plasma cholesterol levels, while streptozotocin, insulin and dexametazone caused an increase. The activity of 3-hydroxy-3-glutaryl CoA reductase in liver and brown adipose tissue changed inversely to the cholesterol level. However, small intestinal enzyme activity was increased by insulin administration inspite of the rise in plasma cholesterol.