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

Hepatic monoacylglycerol acyltransferase (MGAT) (EC 2.3.1.22) is a developmentally-expressed enzyme that catalyzes the stereospecific synthesis of sn-1,2-diacylglycerol from sn-2-monoacylglycerol and long-chain fatty acyl-CoA. In order to study the regulation of MGAT, we developed a rapid assay that can be performed directly on permeabilized HA rat hepatocyte/hepatoma hybrid cells, a line that expresses levels of hepatic MGAT activity and a lipogenic program characteristic of fetal hepatocytes. In permeabilized HA cells, MGAT activity was proportional to the time of incubation and was highly dependent on added sn-2-monoacylglycerol and palmitoyl-CoA. The apparent Km values were 16.6 and 12.7 microM for palmitoyl-CoA and 2-monooleoylglycerol, respectively. Activity was low with the 1(3)- and sn-2-ether analogs of monooleoylglycerol, supporting the conclusion that the cells express the hepatic isoenzyme of MGAT. MGAT activity increased directly with cell density and was unrelated to the number of days in culture. Long-term incubation (2-4 days) of HA cells with various hormones (including triiodothyronine, human placental lactogen, epidermal growth factor, glucagon and growth hormone) showed that only a combination of dexamethasome and insulin resulted in significantly decreased MGAT activity. None of these hormones affected MGAT activity in short-term (0.5-4 h) incubations. These studies suggest that the developmental decline in rat hepatic MGAT activity may be regulated by glucocorticoids and insulin, hormones that increase during and after the second postnatal week.
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PMID:Hepatic monoacylglycerol acyltransferase activity in HA1 and HA7 hepatoma/hepatocyte hybrid cells: regulation by insulin and dexamethasone and by cell density. 841 88

Early and severe loss of body weight associated with pronounced tissue changes developed in rats transplanted with a fast-growing ascites hepatoma (Yoshida AH-130). The protein content showed an early and marked fall in the skeletal muscle, while in the liver it transiently increased 4 days after implantation then declined to values lower than in control animals. Protein loss in gastrocnemius muscle and liver resulted mainly from enhancement of protein catabolism (Tessitore L. et al., Biochem. J., 241: 153-158, 1987). In contrast to the tumour-bearing rats, in the pair-fed animals the initial body weight was maintained, while the protein mass decreased sharply in the liver and moderately in the gastrocnemius muscle. In host animals total plasma protein decreased during the period of tumour growth, while both triglycerides and total cholesterol markedly increased. Glucose remained unchanged even when overt cachexia had developed. The total free amino acid concentration in the plasma of tumour-bearing rats decreased slightly by day 4 and returned to values close to those of controls in the late stages of tumour growth. By contrast, in the pair-fed controls the plasma levels of triglycerides and particularly of total free amino acids and glucose decreased over the whole experimental period, whereas total protein and cholesterol were unchanged. Marked perturbations in the hormonal homeostasis developed early after tumour transplantation. The plasma levels of glucagon, corticosterone and catecholamines rose sharply, while those of insulin and thyroid hormones decreased. Furthermore, high plasma concentrations of prostaglandin E2 (PGE2) and tumour necrosis factor (TNF) were observed over the whole experimental period. IL-1-like activity, TNF and PGE2 were released in vitro from AH-130 cells. These data suggest that the systemic effects of AH-130 tumour on the host rat reflected the interplay of a complex network of factors, including classical hormones and cytokines, all of which likely concur in enhancing tissue protein catabolism.
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PMID:Humoral mediation for cachexia in tumour-bearing rats. 842 75

We applied the differential display RT-PCR (ddRT-PCR) technology to identify estrogen-regulated hepatic genes in the estrogen receptor expressing rat hepatoma cell line Fe33. Three genes of known sequences were detected by the ddRT-PCR approach: IGF binding protein-1 (IGFBP-1), vitamin D-dependent calcium-binding protein (CaBP9k) and major acute phase protein (MAP). Effects of ethinyl estradiol on the mRNA levels of these genes were confirmed by "Northern-blot" analysis. If given in combination with dexamethasone and glucagon, ethinyl estradiol caused 40-, 15- and 11-fold increases in the mRNA steady state level of IGFBP-1, CaBP9k and MAP, respectively, in Fe33 cells 24 h after addition of hormone. Besides ethinyl estradiol, the partial estrogen agonist OH-tamoxifen caused dose dependent effects on expression of MAP and IGFBP-1. Estrogen regulation of the respective genes and the modulatory effects of progesterone (10 mg/animal/day) were studied in ovariectomized rats treated subcutaneously for 14 days with 1 microgram/animal/day estradiol. "Northern-blot" analysis of liver RNA revealed a 6-fold stimulation of IGFBP-1 mRNA levels in estradiol-treated compared to vehicle-treated rats and a weak but detectable increase of MAP mRNA steady state level (1.6-fold) upon estradiol administration. No effect of estradiol treatment could be monitored for CaBP9k in rat liver. Modulatory effects of progesterone on estradiol-stimulated expression in the liver could be monitored for IGFBP-1 only. In an extension of our investigation on the expression of the three genes in rat liver, we determined their expression and hormonal regulation in the uterus of the same animals. In the uterus, estradiol caused an increase in CaBP9k mRNA. In contrast, IGFBP-1 mRNA levels increased dramatically upon progesterone administration, whereas no effect of estradiol treatment could be detected. MAP mRNA levels increased only after coadministration of estradiol and progesterone. In conclusion, the ddRT-PCR proved to be a powerful method to identify estrogen-regulated genes. The study on the hormonal regulation of three genes stimulated by estrogen in Fe33 cells revealed similarities and differences in their regulation in vivo and in vitro.
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PMID:Identification of estrogen regulated genes in Fe33 rat hepatoma cells by differential display polymerase chain reaction and their hormonal regulation in rat liver and uterus. 854 Dec 33

The effect has been studied of various media, hormones and of amino acids on the membrane potential of rat hepatoma cells in culture measured by microelectrode impalement. Cells in Eagle's minimal essential medium plus 5% serum had a value which varied daily from about 5-8 mV, inside negative. The membrane potential of rat hepatocytes was measured to be 8.7 +/- 0.2 mV, inside negative. The membrane potential of the hepatoma cells was decreased by insulin and increased by glucagon. Membrane potential was unaffected by change of medium to Hanks' or Earle's balanced salt solutions or deprivation of serum. It was, however, reduced in cells in phosphate-buffered saline and by reduction of pH. The former effect was shown to be due to the higher [Na+] of phosphate-buffered saline as opposed to the other media. Addition of alanine, glycine, serine, proline and methylaminoisobutyrate all reduced membrane potential by 2-3 mV. Smaller decreases were seen with methionine, leucine and phenylalanine, but none with glutamine, threonine, BCH (2-aminonorborane-2-carboxylic acid) and D-alanine. The results are compared with the effects of similar conditions on aminoisobutyrate uptake. Whilst there was a correlation under some conditions there was not under others. It is concluded that for the hepatoma cells factors additional to the membrane potential must exert some influence on the capacity for amino acid transport.
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PMID:Membrane potential of rat hepatoma cells in culture: influence of factors affecting amino acid transport. 856 68

Plasma membranes from liver of control rats or from chemical-induced hepatoma were prepared. The basal activity of adenylate cyclase was increased significantly in the rat plasma membranes of DEN-induced hepatoma compared to normal tissue. The glucagon-induced response on the cellular effector systems via guanine nucleotide-binding regulatory proteins (G proteins) was inhibited in hepatoma plasma membranes. These findings suggest that in hepatoma membranes, unlike normal hepatic membranes, the response to hormonal stimuli through regulatory G proteins results in a loss of response to glucagon, as well as to GTP plus glucagon or to GTP gamma S. However, the activating effects of forskolin, which catalyses the formation of cyclic AMP from ATP acting on the catalytic subunit, were to some extent retained. The methyltransferase-I behaved in the opposite direction to the adenylate cyclase, showing a decreased activity in hepatoma plasma membranes compared to control membranes. In contrast, the activity of the ecto-5'-nucleotidase was significantly increased in hepatoma. These enzymatic changes have been found to influence the membrane fluidity and to be responsible for the ultrastructural modifications of hepatoma plasma membranes which are induced by chemical carcinogens.
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PMID:Enzymatic, biophysical and ultrastructural changes of plasma membranes in chemical-induced rat hepatoma. 856 46

Chemical-induced peroxisome proliferation in rodent liver is postulated to occur via activation of members of the steroid hormone receptor superfamily, the peroxisome proliferation-activated receptors (PPARs). In the present study, the expression of the predominant liver subtype PPAR alpha was examined and compared to that of acyl-CoA oxidase (ACO), a marker for peroxisome proliferation and a prototype for genes regulated via PPARs. Despite the induction of both mRNA species in vivo by the peroxisome proliferator perfluorodecanoic acid (PFDA), dose response and time course indicate PPAR alpha and ACO are not controlled similarly. Messenger RNA levels for ACO increased rapidly in rat liver and declined over the subsequent 7 days following PFDA administration, while PPAR alpha mRNA increased slower and remained elevated over this period. In addition, PPAR alpha mRNA accumulation in PFDA-treated rats appears to be due primarily to hypophagia as pair feeding and complete caloric restriction result in a large increase in the concentration of this messenger RNA. Nuclear run-on experiments in vivo suggest that, unlike ACO, PFDA as well as caloric restriction results in accumulation of PPAR alpha mRNA which cannot be explained solely by transcriptional activation. These data indicated that PPAR alpha mRNA accumulation has a very small peroxisome proliferator-dependent component and that other factors may be involved. A rat hepatoma cell line was examined to determine the direct effect on peroxisome proliferators on PPAR alpha mRNA. PPAR alpha and ACO mRNA levels were increased rapidly in the rat hepatoma cell line FaO after treatment with PFDA or the prototypical peroxisome proliferator Wy 14,643. In this cell line, PPAR alpha mRNA levels are not affected by glucagon or insulin and in addition to peroxisome proliferators are induced in this cell line by oleic acid and dexamethasone. The latter treatment had the greatest effect on PPAR alpha mRNA accumulation while having a minimal effect on ACO mRNA. Treatment of FaO cells with actinomycin D prior to Wy 14,643 abolished ACO and PPAR alpha mRNA accumulation, demonstrating that there must be a transcriptional component of the peroxisome proliferator response. Therefore, although PPAR alpha is responsive to peroxisome proliferators and direct effects are observed in cell cultures, mRNA accumulation in vivo is predominantly posttranscriptional, and endogenous regulators such as glucocorticoids may play critical roles in the tissue- and developmentally specific expression of this steroid hormone receptor.
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PMID:Regulation of peroxisome proliferator-activated receptor-alpha mRNA in rat liver. 861 Oct 35

Surgical resection has been the standard approach for primary and metastatic liver tumors. Long-term survival, however, is limited because of recurrence or hepatic decompensation. Failure of chemotherapeutic regimens or liver transplantation (OLT) to prevent recurrence has resulted in the need for multimodality therapies. We report our experience with preoperative hepatic arterial chemoembolization (CET) followed by OLT in highly select patients. Over a 33-month period, 23 of 41 patients (56%) referred with primary (n = 16) or metastatic neuroendocrine (n = 7) liver tumors met eligibility requirements. Despite mild, self-limited chemical hepatitis, CET was well tolerated in all but three elderly patients who succumbed to liver failure. Four of five patients ultimately received OLT. Three are alive and free of disease at a mean followup of 17 months, one died of recurrent hepatocellular carcinoma, and one (NET) remains well at 33 months with elevated glucagon levels but no measurable disease. All NET patients are alive with resolution of hormonal symptoms. Four of five noncirrhotic patients died of disease, and one has progressive tumor growth. Although OLT following CET achieves superior survival, its application is limited to a minority of patients with such tumors. Careful pretreatment staging and patient selection combined with caution in the use of CET in elderly cirrhotic patients is critical to the success of such therapies.
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PMID:Intrahepatic arterial chemoembolization for hepatocellular carcinoma and metastatic neuroendocrine tumors in the era of liver transplantation. 875 63

Lipoprotein lipase (LPL) activity is known to be synthesized, active and functional in the 1-day-old rat liver: it peaks just at birth triggered by parturition. During suckling LPL mRNA, LPL synthesis and LPL activity are still high at 5 days and then fade reaching adult values at weaning. How LPL expression is gradually extinguished is not known. Therefore we studied the effect of different doses of several hormones on LPL activity released by incubated hepatocytes from 5-day-old rats. In the presence of heparin the release of LPL activity in the medium was linear until 3 h and was always significantly increased vs. without heparin. At 3 h in the presence of heparin the main hormonal effects were: dose-dependent increase (30-60%) with dexamethasone; dose-dependent increase (20-60%) with glucagon; dose-independent decrease (50-60%) with ethinylestradiol, testosterone, progesterone and prolactin; no effect with insulin; 20-40% increase with adrenaline < 1 mM but 40-50% decrease with noradrenaline < 10 microM. Increase of LPL release by glucagon and adrenaline agrees with the increased LPL expression we previously found in an undifferentiated hepatoma cell line when the adenylate cyclase/protein kinase A pathway was activated. The effect of glucagon is concordant with our previous observations that fasting increases liver LPL activity in neonatal rats. The high estradiol levels known to be present in male and female 9-19-day-old rats might contribute to liver LPL extinction during suckling.
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PMID:Hormonal regulation of lipoprotein lipase activity from 5-day-old rat hepatocytes. 882 70

Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the rate-limiting step in hepatic gluconeogenesis. Glucagon (via the second messenger cAMP), retinoic acid, and glucocorticoids stimulate transcription of the PEPCK gene, whereas insulin and phorbol esters have a dominant inhibitory effect. We now show that oxidative and chemical stress (hydrogen peroxide and sodium meta-arsenite, respectively) also produce a dominant inhibitory effect, both on the endogenous PEPCK gene and on a stably transfected PEPCK-chloramphenicol acetyl transferase (CAT) fusion gene. Wortmannin, an inhibitor of 1-phosphatidylinositol 3-kinase (PI 3-kinase), blocks the inhibition of glucocorticoid and cAMP-induced PEPCK gene transcription by insulin; however, it has no effect on the inhibition elicited by oxidative or chemical stress. Thus, the mechanism(s) used by hydrogen peroxide and sodium meta-arsenite to regulate PEPCK gene expression are PI 3-kinase independent. This suggests that these agents operate by a pathway distinct from that used by insulin or that the pathways converge at a point downstream of PI 3-kinase. The reactivating kinase (RK, also known as p38 mitogen activated protein kinase) is induced by insulin, hydrogen peroxide, or sodium meta-arsenite in hepatoma cells, and these effects are blocked by SB203580, a selective inhibitor of RK. However, SB203580 has no effect on the ability of any of these agents to regulate PEPCK-CAT fusion gene expression. Thus, although RK has a role in the regulation of lymphokine gene expression in monocytes, it is not required for the regulation of PEPCK expression by either insulin or oxidative and chemical stress in hepatoma cells.
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PMID:Oxidative and chemical stress mimic insulin by selectively inhibiting the expression of phosphoenolpyruvate carboxykinase in hepatoma cells. 897 Oct 75

Hepatic metabolism and gene expression are among other regulatory mechanisms controlled by the cellular hydration state, which changes rapidly in response to anisotonicity, concentrative substrate uptake, oxidative stress, and under the influence of hormones such as insulin and glucagon. Differential screening for cell volume sensitive transcripts in a human hepatoma cell line revealed a gene for a putative serine/threonine kinase, h-sgk, which has 98% sequence identity to a serum- and glucocorticoid regulated kinase, sgk, cloned from a rat mammary tumor cell line. h-sgk transcript levels were strongly altered during anisotonic and isotonic cell volume changes. Within 30 min h-sgk RNA was, independent of de novo protein synthesis, induced upon cell shrinkage and, due to a complete stop in h-sgk transcription, reduced upon cell swelling. Comparable changes of sgk transcript levels were observed in a renal epithelial cell line. h-sgk mRNA was detected in all human tissues tested, with the highest levels in pancreas, liver, and heart. The putative serine/threonine protein kinase h-sgk may provide a functional link between the cellular hydration state and metabolic control.
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PMID:Cloning and characterization of a putative human serine/threonine protein kinase transcriptionally modified during anisotonic and isotonic alterations of cell volume. 911 8


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