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)

The procedure of Berry and Friend for isolation of intact hepatocytes has been adapted to mouse livers. The ultrastructure of these cells was satisfactorily preserved. Isolated mouse hepatocytes secreted proteins and triacylglycerols. These secretory processes were inhibited by colchicine, indicating a likely involvement of the microtubular system for their normal occurrence. Ultracentrifugation of medium incubated with hepatocytes, followed by electrophoresis and electron microscopic examination of the floating fraction (density less than 1.006) allowed to conclude that secreted triacylglycerols were very low density lipoproteins. Glycogenolysis and lipogenesis were stimulated or inhibited, respectively, by low concentrations of glucagon (10(-10) M). Other metabolic parameters were influenced by the hormone but were less sensitive to its action. Inhibition of lipogenesis by glucagon was associated with a decrease in acetyl CoA carboxylase activity. This decrease does not appear to be related to intracellular fatty acyl-CoA accumulation secondary to hepatic lipase activation by the hormone. Insulin was effective alone or counteracted glucagon effects on lipogenesis or glycogenolysis only when exposure of cells to collagenase was held minimal. This suggests that, during isolation of hepatocytes, insulin receptors may, for unknown reasons, be more fragile than those of glucagon.
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PMID:Secretory processes, carbohydrate and lipid metabolism in isolated mouse hepatocytes. Aspects of regulation by glucagon and insulin. 17 77

Lipoprotein lipase and hepatic lipase are members of the lipase gene family sharing a high degree of homology in their amino acid sequences and genomic organization. We have recently shown that isolated hepatocytes from neonatal rats express both enzyme activities. We show here that both enzymes are, however, differentially regulated. Our main findings are: (i) fasting induced an increase of the lipoprotein lipase activity but a decrease of the hepatic lipase activity in whole liver, being in both cases the vascular (heparin-releasable) compartment responsible for these variations. (ii) In isolated hepatocytes, secretion of lipoprotein lipase activity was increased by adrenaline, dexamethasone and glucagon but was not affected by epidermal growth factor, insulin or triiodothyronine. On the contrary, secretion of hepatic lipase activity was decreased by adrenaline but was not affected by other hormones. (iii) The effect of adrenaline on lipoprotein lipase activity appeared to involve beta-adrenergic receptors, but stimulation of both beta- and alpha 1-receptors seemed to be required for the effect of this hormone on hepatic lipase activity. And (iv), increased secretion of lipoprotein lipase activity was only observed after 3 h of incubation with adrenaline and was blocked by cycloheximide. On the contrary, decreased secretion of hepatic lipase activity was already significant after 90 min of incubation and was not blocked by cycloheximide. We suggest that not only synthesis of both enzymes, but also the posttranslational processing, are under separate control in the neonatal rat liver.
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PMID:Lipoprotein lipase and hepatic lipase activities are differentially regulated in isolated hepatocytes from neonatal rats. 156 12

Cultured rat hepatocytes release the enzyme hepatic lipase. In this study we investigated the effect of cell density on this metabolic function under a variety of experimental conditions. The release of hepatic lipase from cultured rat hepatocytes exhibits a cell-density dependence, the secretion per mg cell protein being increased with increasing cell density. When cell density dependence was taken into consideration no significant effect of insulin on the release of hepatic lipase from cultured hepatocytes was observed, whereas glucagon suppressed the release. Glucose stimulating the release of the enzyme, especially in cultures with high cell density.
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PMID:Cell-density-dependent release of hepatic lipase from cultured rat hepatocytes. 264 7

Post-heparin lipase activities were measured in normolipemic men with complaints suggestive of symptomatic coronary artery disease. A study group, who showed diffuse atherosclerotic narrowing of the coronary vessels, assessed by a quantitative computer-assisted analysis method, had a lowered hepatic lipase in comparison with a group with normal angiograms. Lipoprotein lipase was lower in the study group but well within the normal range and not statistically different. Some related hormones (cortisol, estradiol, testosterone and glucagon) were different in the two groups while others (insulin, human growth hormone, prolactin, thyroid hormones) were not. The results are discussed in view of the proposed role of hepatic lipase in the uptake of HDL-cholesterol by the liver.
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PMID:Post-heparin lipases, lipids and related hormones in men undergoing coronary arteriography to assess atherosclerosis. 635 16

The relationship between obesity and alterations in adipose tissue metabolism and lipid transport was studied in fourteen obese subjects before and after a weight reduction of 4-22 kg. Blood glucose and plasma insulin patterns after peroral glucose intake improved significantly, and plasma glucagon levels decreased markedly after treatment. Plasma triglyceride and total cholesterol levels were not altered, but there was a 20% (P less than 0.05) increase in HDL concentrations. Plasma free fatty acid and glycerol concentrations decreased, in parallel to a decrease in lipolysis rate in vitro. Lipoprotein lipase and hepatic lipase activities in postheparin plasma, as well as the intravenous fat tolerance test, were normal and did not change significantly after weight loss. Lipoprotein lipase activity in adipose tissue, expressed per cell, was elevated and did not change after weight reduction. Also, the enzyme activity did not increase after glucose intake before or after treatment. The lack of effect on lipoprotein lipase activity and regulation in combination with significant improvements of other aspects of lipid and glucose transport is consistent with the view that alterations in LPL activity and regulation may represent an early and possibly primary defect in the development of obesity.
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PMID:Effects of weight reduction on plasma lipoproteins and adipose tissue metabolism in obese subjects. 680 Aug 25

Triacylglycerol lipase activities of homogenates and subcellular fractions of rat liver were measured under optimal conditions at pH 7.5 using emulsified tri[1-14C]oleoylglycerol as substrate. Twenty-four hr after administration of streptozotocin, hepatic alkaline lipase activity was 39% of normal, and this lower level of activity was observed at 72 hr and 7 days, after streptozotocin injection. After 24 hr of starvation, lipase activity also was significantly lower (35%) than normal. Insulin (35 U regular/kg body weight) had no acute (90 min) effect on the hepatic lipase activity of either normal or diabetic rats. Chronic insulin administration (4 subcutaneous injections of 10 U protamine zinc insulin/kg at 16-hr intervals) to normal rats provoked a 40% increase in hepatic lipase activity. Diabetic rats given the same insulin treatment showed lipase activity that was significantly higher (155%) than normal. Lipase activity fell to 65% of normal when insulin was withheld (32 hr) from diabetic rats given chronic insulin therapy. Intracardial injection of glucagon (1 mg/kg) into normal rats had no acute (30 min) effect on hepatic alkaline lipase activity. Hepatic alkaline lipase activity varied independently from the concentrations of either glucose or triacylglycerol in the plasma. However, there was an apparent negative correlation between this lipase activity and the concentration of fatty acids in the plasma; lipase activity was highest when fatty acid concentrations were lowest, and lowest when fatty acid concentrations were elevated. From these data we conclude: 1) changes in hepatic alkaline lipase activity ware provoked by chronic, but not acute, alteration of the hormonal and metabolic status of the rat, and 2) changes in hepatic alkaline lipase activity may be mediated through changes in the levels of circulating fatty acids presented to the liver, but the effect is not an immediate one.
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PMID:Hepatic triacylglycerol lipase activities after induction of diabetes and administration of insulin or glucagon. 704 62

As part of an ongoing search for diabetes susceptibility loci, we tested linkage with non-insulin-dependent diabetes mellitus (NIDDM) for 19 candidate loci or regions chosen for their potential to affect directly or indirectly the action of insulin. Loci were associated with insulin resistance, known effects on lipid metabolism, or effects on glucose metabolism or insulin action. Loci included the insulin-responsive (GLUT4) glucose transporter, hexokinase 2, glucagon, growth hormone, insulin receptor substrate 1 (IRS1), phosphoenolpyruvate carboxykinase, hepatic and muscle forms of pyruvate kinase, hepatic phosphofructokinase, the apolipoprotein B and the apolipoprotein A2 cluster, lipoprotein lipase, hepatic triglyceride lipase, the very-low-density-lipoprotein receptor, and the Pima insulin resistance locus on chromosome 4. For several candidates, no specific informative marker was available; consequently, we tested the surrounding region with highly informative markers. These regions included the diabetes-associated ras-like gene, rad, and the cholesterol ester-transfer gene, both mapped to chromosome 16. Additionally, we tested for linkage with markers at the tumor necrosis factor-alpha gene and the Friedreich's ataxia region. All regions were tested for linkage with microsatellite polymorphisms in > 450 individuals from a minimum of 16 Caucasian families under parametric (LINKAGE 5.1) and nonparametric (affected pedigree member) models.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Linkage analysis of 19 candidate regions for insulin resistance in familial NIDDM. 758 21

Rainbow trout were used to investigate the hormonal regulation by glucagon and insulin of hepatic triacylglycerol (TG) lipase activation. Two purified preparations of the trout hepatic TG lipase enzyme, the 110,000-g preparation and the resuspended ammonium sulfate fraction (ASF), were activated up to 58% with (in mM) 0.5 ATP, 0.01 cAMP, 5 MgCl2, and exogenous protein kinase over control levels. ATP or cAMP alone had no effect on activation. Activation of the trout hepatic lipase was reversible; complete inactivation of the ASF was obtained within 3 h in the presence of exogenous phosphorylase phosphatase. Adenosine 3',5'-cyclic monophosphate (cAMP)/ATP-dependent 32P-phosphorylation of trout hepatic lipase was observed within 5 min of incubation with the cAMP/ATP-Mg2+ activation system and 25 microCi [32P]ATP. Hormonal modulation of trout hepatic lipase phosphorylation was studied in isolated hepatocytes. Hepatocytes were incubated with [32P]-monopotassium phosphate for 3 h, then exposed to mammalian glucagon (GLU). Within 5 min, increased lipolysis was accompanied by a 95% increase in phosphorylation of the enzyme. Mammalian insulin (INS) depressed GLU-stimulated phosphorylation by 56% and inhibited GLU-stimulated lipolysis. These results indicate that GLU and INS modulate lipolysis in trout liver by altering phosphorylation of the TG lipase enzyme.
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PMID:Glucagon and insulin regulate lipolysis in trout liver by altering phosphorylation of triacylglycerol lipase. 834 95

In the view of lipid metabolism, adipose tissue and liver are the most important tissues for 17-beta-estradiol, the main estrogen in women's body. The lack of estrogens in women after menopause may cause coronary heart disease. It is considered, that 25 to 50% of positive effect of estrogens which are given to postmenopausal women is connected with their action on lipid metabolism. Blood plasma parameters which characterize lipid metabolism return to their physiological values during estrogens therapy. Estrogens are transferred to adipose tissue cells and liver cells by endocrine and paracrine way. They are also produced in these cells from androgens. In adipocytes 17-beta-estradiol can be stored as its esters with long-chain fatty acids. It was proved that estrogens receptors are present in adipocytes and hepatocytes but their density is much lower than in gonads. On the cellular level estrogens regulate mRNA production for particular proteins among which there are proteins involved in lipid metabolism. In adipose tissue 17-beta-estradiol has a direct effect on lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL). In the case of the first enzyme its synthesis is faster, while the synthesis of the latter is slower. On the other hand, indirect action of estrogens on adipose tissue is connected with the stimulation of the releasing of other hormones which increase HSL activity. To this group of hormones there belong catecholamines, growth hormone (GH) and glucagon. In liver 17-beta-estradiol regulates the rate of synthesis of structural apolipoproteins for VLDL and HDL. 17-beta-estradiol reduces the rate of apoB-100 synthesis, while stimulates apoA-I and apoA-II synthesis. HDL fraction containing apoA-I and apoA-II is necessary for chylomicrons and VLDL degradation as well as direct and indirect cholesterol transport to liver. Moreover, in hepatocytes estrogens stimulate the synthesis of apoC-III, while they decrease the synthesis of hepatic lipase (HL). In conclusion, 17-beta-estradiol by regulating lipid metabolism in adipocytes and hepatocytes modulates the concentration of lipid substances in plasma. The lack of 17-beta-estradiol leads likely to various lipid metabolism disorders in women after menopause. Estrogens therapy in these postmenopausal women may result in the improvement of lipid metabolism.
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PMID:[The role of estrogens in hormonal regulation of lipid metabolism in women]. 974 Nov 94

The incidence of nonalcoholic fatty liver disease (NAFLD) keeps rising year by year, and NAFLD is rapidly becoming the most common liver disease worldwide. Clinical studies have found that glucagon-like peptide-1 (GLP-1) analogue, liraglutide (LRG), cannot only reduce glucose levels, but also improve hepatic lipase, especially in patients also with type 2 diabetes mellitus (T2DM). In addition, enhancing autophagy decreases lipid accumulation in hepatocytes. The aim of the present study is to explore the effect of LRG on hepatocyte steatosis and the possible role of autophagy. We set up an obesity mouse model with a high-fat diet (HFD) and induced hepatocyte steatosis with free fatty acids (FFA) in human L-O2 cells. LRG and two inhibitors of autophagy, Chloroquine (CQ) and bafilomycin A1 (Baf), were added into each group, respectively. The lipid profiles and morphological modifications of each group were tested. Immunohistochemistry, immunofluorescence staining and transmission electron microscopy (TEM) were used to measure autophagy in this study. The autophagy protein expression of SQSTM1 (P62), and LC3B, along with the signaling pathway proteins of mTOR, phosphorylated mTOR (p-mTOR), AMPK, phosphorylated AMPK (p-AMPK) and Beclin1, were evaluated by western blot. Our results showed that LRG improved hepatocyte steatosis by inducing autophagy, and the AMPK/mTOR pathway is involved. These findings suggest an important mechanism for the positive effects of LRG on hepatic steatosis, and provide new evidence for clinical use of LRG in NAFLD.
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PMID:GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway. 2720 76


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