Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Completely diverting portacaval shunt (Eck's fistula) in dogs causes hepatocyte atrophy, disruption of hepatocyte organelles, fatty infiltration and low-grade hyperplasia. The effect of hepatic growth regulatory substances on these changes was assessed by constantly infusing test substances for four postoperative days after Eck's fistula into the detached left protal vein above the shunt. The directly infused left lobes were compared histopathologically with the untreated right lobes. In what has been called an hepatotrophic effect, stimulatory substances prevented the atrophy and increased hepatocyte mitoses. Of the hormones tested, only insulin was strongly hepatotrophic; T3 had a minor effect, and glucagon, prolactin, angiotensin II, vasopressin, norepinephrine and estradiol were inert. Insulin-like growth factor, hepatic stimulatory substance, transforming growth factor-alpha and hepatocyte growth factor (also known as hematopoietin A) were powerfully hepatotrophic, but epidermal growth factor had a barely discernible effect. Transforming growth factor-beta was inhibitory, but tamoxifen, interleukin-1 and interleukin-2 had no effect. The hepatotrophic action of insulin was not altered when the insulin infusate was mixed with transforming growth factor-beta or tamoxifen. These experiments show the importance of in vivo in addition to in vitro testing of putative growth control factors. They illustrate how Eck's fistula model can be used to screen for such substances and possibly to help delineate their mechanisms of action.
 ...
PMID:Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula. 191 68

An organ-culture system has been used to investigate the effect of certain gastrointestinal peptides on the morphology and cell proliferation of explants of azoxymethane (AOM)-treated colonic mucosa. Our aim was to ascertain whether such factors play a direct part in the maintenance of hyperplastic changes in the large intestine. Explants of AOM-treated colonic mucosa from 15 animals were maintained in a serum-free medium in the presence of either gastrin-17 (250 pg/ml and 250 ng/ml), peptide YY (80 pmol/l and 160 pmol/l) epidermal growth factor (EGF) (10 ng/ml and 100 ng/ml) or the C-terminal fragment of glucagon-37 (30 pmol/l) for a period of up to 7 days. Other explants (controls) received fresh medium only each day. After 1, 2, 3, 5 and 7 days of culture both experimental and control explants received vincristine (4 micrograms/ml) for 3 h prior to fixation. The proportion of vincristine-arrested metaphases within the explants was determined together with crypt length. Neither gastrin nor peptide YY was found to influence cell division at either concentration. Despite an initial inhibitory effect, both concentrations of EGF exerted a trophic effect which increased with time. The glucagon-37 fragment caused an immediate increase in proliferation which then declined as time progressed. None of these factors, however, were able to maintain the hyperplastic changes seen in the pre-culture samples of AOM-treated mucosae.
 ...
PMID:Effects of gastrointestinal peptides on azoxymethane-treated colonic mucosa in vitro. 193 85

The effect of fasting on hepatic endothelial lipase activity in the liver of adult rats was investigated. We found that, both in male and female rats, fasting produced a progressive decrease of the hepatic endothelial lipase activity. Upon refeeding, the activity returned to control values in 48 h. In isolated livers from fed male rats, a sharp peak of hepatic endothelial lipase activity appeared in the perfusate upon heparin addition. It accounted for 75% of the total activity (heparin-released + residual) of the tissue. Fasting (24 h) decreased the heparin-releasable activity, and this effect was responsible for most of the decrease found in whole tissue. We suggest that the effect might be due to a decreased synthesis and/or secretion of the enzyme by hepatocytes, since isolated hepatocytes from fasted rats, incubated at 37 C, released 65% less activity to the incubation medium than hepatocytes from fed rats. Adrenaline, but not insulin, glucagon, dexamethasone, epidermal growth factor, or T3, decreased the amount of hepatic endothelial lipase activity released by hepatocytes isolated from fed rats. The effect of adrenaline appears to be mediated by alpha 1-receptors since phenylephrine but not isoprenaline reproduced, and prazosin but not propranolol blocked, the effect of the catecholamine. In the presence of cycloheximide, adrenaline also decreased the amount of activity released. We suggest that, in our incubation conditions (up to 3 h), the hormone affects the posttranslational processing of the enzyme. In vivo administration of prazosin blocked the effect of both noradrenaline and fasting on hepatic endothelial lipase activity in whole liver. Those results suggest that catecholamines are involved in the decreased hepatic endothelial lipase activity found in the liver of fasted rats, and points out the role of these hormones in the acute modulation of an enzyme involved in reverse cholesterol transport.
 ...
PMID:Involvement of catecholamines in the effect of fasting on hepatic endothelial lipase activity in the rat. 193 90

The hormonal regulation of GH receptors was studied by measuring specific binding of [125I]human GH to primary cultured rat hepatocytes. The binding of labeled GH to primary cultured hepatocytes decreased during culture, but addition of dexamethasone (100 nM) compensated for this decrease and even increased GH binding. After addition of dexamethasone, the binding increased to a maximum after 10 h, and after 24 h was about 6 times that of control cells. Glucagon (100 nM) did not have any significant effect on GH binding by itself, but enhanced the increased binding caused by dexamethasone about 1.5-fold. For this effect, glucagon could be replaced by (Bu)2cAMP. Insulin (10 nM) and epidermal growth factor (20 ng/ml) reduced the increase by dexamethasone plus glucagon by about half. Scatchard plot analysis showed that the changes of GH binding induced by various hormones were due to changes in the number of binding sites without significant changes in their affinity. The GH bound to dexamethasone or dexamethasone plus glucagon-treated cells was not replaced by unlabeled ovine PRL. This strongly suggests that the number of somatogenic (GH) receptors may be subject to hormonal regulation: dexamethasone alone or with glucagon may induce GH receptors, whereas insulin and EGF may suppress the induction of GH receptors. These patterns of hormonal regulations were almost the same as those of proteins whose expressions were known to be differentiated functions of liver. On the other hand, the increase of GH binding by dexamethasone was inhibited by cycloheximide and actinomycin D, though the GH binding was inhibited by cycloheximide, but not by actinomycin D in the cells cultured without dexamethasone. This result suggests that the increased binding induced by dexamethasone is dependent on the synthesis of new protein and is probably regulated at a pretranslational level.
 ...
PMID:Hormonal regulation of growth hormone receptors in primary cultured rat hepatocytes. 216 18

Although several lines of evidence implicate cyclic AMP in the humoral control of liver growth, its precise role is still not clear. To explore further the role of cyclic AMP in hepatocyte proliferation, we have examined the effects of glucagon and other cyclic AMP-elevating agents on the DNA synthesis in primary cultures of adult rat hepatocytes, with particular focus on the temporal aspects. The cells were cultured in a serum-free, defined medium and treated with epidermal growth factor (EGF), insulin, and dexamethasone. Exposure of the hepatocytes to low concentrations (10 pM-1 nM) of glucagon in the early stages of culturing (usually within 6 h from plating) enhanced the initial rate of S phase entry without affecting the lag time from the plating to the onset of DNA synthesis, whereas higher concentrations inhibited it. In contrast, glucagon addition at later stages (24-45 h after plating) produced only the inhibition. Thus, if glucagon was added at a time when there was a continuous EGF/insulin-induced recruitment of cells to S phase, the rate of G1-S transition was markedly decreased within 1-3 h. This inhibitory effect occurred at low glucagon concentrations (ID50 less than 1 nM) and was mimicked by cholera toxin, forskolin, isobutyl methylxanthine, and 8-bromo cyclic AMP. The results indicate that cyclic AMP has dual effects on hepatocyte proliferation with a stimulatory modulation early in the prereplicative period (G0 or early G1), and a marked inhibition exerted immediately before the transition from G1 to S phase.
 ...
PMID:Dual effects of glucagon and cyclic AMP on DNA synthesis in cultured rat hepatocytes: stimulatory regulation in early G1 and inhibition shortly before the S phase entry. 216 4

Previous studies on the age and sex dependency of the ganglioside patterns in rat liver in vivo and the concomitant determination of the activities of some enzymes involved in these pathways revealed the prominent role of the sialylation of GM3 to GD3 in determining the flow to the mono (a)- and polysialo (b)-series, respectively. Here, the influence of hormones on the activities of GM3 and GD3 synthases in isolated hepatocytes was studied. The combination of several factors (insulin, glucagon, epidermal growth factor, glucocorticoids) was found to be necessary for maintaining in vivo activity levels of GD3- but not of GM3-synthase.
 ...
PMID:Sialyltransferase activities in cultured rat hepatocytes. 220 41

Gastrin has been shown to be an important trophic hormone for the mucosa of the stomach and the proximal intestine. In the present study the effect of gastrin on liver regeneration after partial hepatectomy in rats was investigated. After partial hepatectomy a significant rise in the concentration of gastrin in portal venous blood was found six, 12, and 18 hours after 70% hepatectomy. The effect of changes in the endogenous gastrin concentration on the liver regeneration was investigated in rats subjected to antrectomy or to fundectomy. Partial hepatectomy was done three weeks after the primary surgery. We found antrectomy to decrease liver regeneration, whereas fundectomy had no effect. Administration of pentagastrin 300 micrograms/kg sc three times daily for two and four days after partial hepatectomy significantly increased the rate of liver regeneration compared with controls. This study suggests that gastrin has a hepatotrophic effect. Whether this effect is caused by a direct action of gastrin on the hepatocytes or it is an indirect effect mediated by for instance insulin, glucagon or epidermal growth factor has to be further investigated.
 ...
PMID:Effect of gastrin on liver regeneration after partial hepatectomy in rats. 231 36

Hormonal regulation in the production of a plasminogen activator (PA) was studied in rat hepatocytes in primary culture. Insulin and epidermal growth factor had no effect on the hepatic PA activity. However, glucagon and epinephrine augmented the activity, whereas dexamethasone suppressed it by lowering the production of hepatic PA rather than by inducing plasmin inhibitors or a plasminogen activator inhibitor (PAI). Dibutyryl cAMP, an analogue of cAMP, also augmented hepatic PA activity. The augmented activity level was lowered by either H-8, cycloheximide, or actinomycin D, suggesting that A-kinase and protein biosynthesis are closely associated with the augmentation. Glucocorticoid and hormones that act to raise the intracellular cAMP level may participate in hepatic PA production by the liver.
 ...
PMID:Hormonal regulation of plasminogen activator production by rat hepatocytes in primary culture. 238 27

Fluorescence photobleaching was used to measure the effect of epidermal growth factor (EGF), insulin, and glucagon on the nuclear transport of fluorescent-labeled dextrans across the nuclear pore complex. EGF and insulin were found to stimulate transport approximately 200%, while boiling these polypeptide growth factors greatly diminished this enhancement activity. Glucagon demonstrated no enhancement effect. The nuclear transport enhancement effects were observed at EGF and insulin concentrations that elicit the various physiological responses, e.g., nanomolar range.
 ...
PMID:Epidermal growth factor and insulin stimulate nuclear pore-mediated macromolecular transport in isolated rat liver nuclei. 243 40

To evaluate the possible role of various hormones on fetal pancreas development, late gestational fetal rat pancreata (20 days) were cultured in a serum-free medium for 6 days in the presence of cholecystokinin-octapeptide (CCK-8), epidermal growth factor, triiodothyronine, or glucagon with or without dexamethasone. In the absence of any added hormone, the tissue amylase activity declined very rapidly. Epidermal growth factor alone (4.10(-7) M) could not preserve the amylase activity, whereas triiodothyronine (0.1 microM) and glucagon (4 micrograms/ml) had a deleterious effect that was prevented by the addition of DXM (3.10(-6) M). In the presence of CCK-8 (2.10(-11) M) 50 and 30% of the amylase activity was maintained on the 2nd and the 4th day of culture, respectively. The CCK-8 effect was dose dependent and was inhibited by asperlicin (10 microM). The combination of CCK-8 and dexamethasone maintained more than 80% of the amylase activity in the fetal pancreas explants through 4 days of culture. Fetal pancreas cultured in this optimal medium and treated with streptozotocin (10(-7) M) during the 1st day of culture showed a significantly lower tissue amylase activity on the 4th and 6th days than those not treated with streptozotocin. The streptozotocin effect was attenuated when insulin (0.1 U/ml) was added. These data suggest that, in addition to the well-known effect of glucocorticoid on enzyme activities in the fetal pancreas, two additional hormones, CCK and insulin, could play a role in the modulation of pancreatic amylase activity in the fetal rat.
 ...
PMID:The effect of cholecystokinin-octapeptide, insulin, glucagon, triiodothyronine, and epidermal growth factor on amylase activity in fetal pancreas in vitro. 245 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>