Opposite Effects of Insulin and Glucagon in Acute Hormonal Control of Hepatic Lipogenesis

Beynen, A.C.; Vaartjes, W.J.; Geelen, M.J.H.

doi:10.2337/diab.28.9.828

Cited by 100 publications

(62 citation statements)

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“…The insulin-induced increases in cellular triglyceride content appeared to be principally or exclusively due to inhibition of the secretion of VLDL triglycerides. The effect was present at both high and low concentrations of glucose, supporting the view that it was not exclu- (11), isolated perfused liver (7,8,10), and hepatocytes in suspension (12,19). Insulin may enhance the conversion of acetyl-CoA to fatty acids (41) and it has been suggested that it might reduce the entry of these into mitochondria for f(-oxidation because of inhibition of acyl-carnitine transferase by malonyl-CoA produced as an intermediate in fatty * =ãcid synthesis (42).…”

Section: Discussionsupporting

confidence: 60%

“…The methods for measurement of VLDL secretion in whole animals also do not allow short-term effects to be studied since they require measurements to be made over several hours or days and even then there is disagreement about the theoretical models used in the interpretation of results (5). Studies of isolated liver tissues have thus proved attractive since the environment may be precisely defined and much information has been gained from studies of isolated perfused liver (6-10), perfused liver slices (11), and isolated hepatocytes in suspension (12). These methods, however, have the limitation that the viability of the isolated liver or hepatocytes can only be maintained for a short time during which they may still be under the influence of conditions prevailing in the animal at the time of their isolation.…”

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confidence: 99%

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Effects of Insulin and Glucose on Very Low Density Lipoprotein Triglyceride Secretion by Cultured Rat Hepatocytes

Durrington¹,

Newton²,

Weinstein³

et al. 1982

J. Clin. Invest.

215

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A B S T R A C T The effect of insulin on hepatic triglyceride synthesis and secretion is controversial. Previously, we have described a cell culture system of adult rat hepatocytes that synthesize and secrete very low density lipoprotein (VLDL) triglycerides with small and irreproducible effects of insulin on triglyceride metabolism. To study the primary effects of insulin on hepatic triglyceride metabolism a method was developed utilizing fibronectin-coated culture dishes that allowed adhesion, spreading, and maintenance of hepatocytes for 2-3 d in the absence of serum and insulin. This culture system allowed mass measurements of both cellular and secreted VLDL triglycerides for long time periods after the addition of physiological concentrations of insulin to hormone-free culture medium. In the absence of insulin and after an initial 4 h in culture, the medium was replenished and triglyceride mass was measured at the end of 18-h incubations. VLDL triglyceride accumulated in the culture medium at a linear rate over this time-course with increasing accumulation as the medium glucose concentration was raised from 2.5 to 25 mM glucose (1.77±0.24 to 3.09±0.76 yg triglyceride/mg cell protein per h). There was no apparent significant lipolysis or hepatocellular reuptake of secreted VLDL triglycerides. In the absence of insulin cellular triglyceride levels were unchanged between 3 and 24 h in culture while insulin (50-500 gU/ml) significantly increased cellular triglyceride content at all glucose concentrations tested (0-25 mM). The addition of insulin to the culture medium progressively reduced the rate of VLDL triglyceride secretion accompanied by an increase in cellular triglyceride at insulin concentrations > 50 ,U/ml. Most or all of the observed increase in cell triglyceride content could in all experiments be accounted for by the insulin-induced inhibition of VLDL secretion. Incorporation of [2-3H]glycerol into cellular and VLDL triglycerides as a function of insulin concentration was also measured. Glycerol incorporation data at 20-22 h after plating of the cells closely paralleled the insulin-induced changes in cellular and VLDL triglyceride as determined by mass analysis. The observed effects of insulin occurred at concentrations close to the physiological range and suggest that the direct hepatic effect is to suppress VLDL secretion although the net effect in vivo will clearly reflect many additional accompanying changes.

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Section: Discussionsupporting

confidence: 60%

mentioning

confidence: 99%

Effects of Insulin and Glucose on Very Low Density Lipoprotein Triglyceride Secretion by Cultured Rat Hepatocytes

Durrington¹,

Newton²,

Weinstein³

et al. 1982

J. Clin. Invest.

215

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“…The plasma levels of glucagon and corticosterone, however, were elevated in our waterdeprived rats, which might account for the alterations of lipid metabolism. It is known that glucagon enhances lipolysis and decreases fatty acid synthesis; corticosterone also increases lipolysis äs the main adrenocortical honnone of the rat; its effect on fatty acid synthesis is not known (24,25). Glucagon enhances formation of ketone compounds (26); in our study these were not measured in the plasma.…”

Section: Pathögenetic Mechanismscontrasting

confidence: 45%

Metabolic Effects of Water Deprivation

Hohenegger¹,

Laminger²,

Om³

et al. 1986

Clinical Chemistry and Laboratory Medicine

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Summary ·1. Under the conditions öf pair feeding, water-deprived rats predominantly use fat äs a metabolic fuel, whereas total energy turnover äs measured by oxygen consumption is not altered. t.2. Plasma free fatty acids are elevated in dehydrated rats, indicating enhanced lipolysis.. 3. Reduced hepatic fatty acid synthesis and reduced triacylglycerol secretion into the blood seem to be the main factors for the decfease of plasma triacylglycerol, observed 48 hours after the onset of water j deprivation.4. Enhanced plasma levels of corticosterone (about 100%) and glucagon (about 50%) may contribute to the ; metabolic Situation observed in water deprivation.

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“…Polymerase Chain Reaction-Reverse transcription of 2 g of total RNA was carried out with 0.2 g of oligo(dT) [12][13][14][15][16][17][18] primer for 50 min at 42°C, and real time quantitative polymerase chain reaction was done with an ABI PRISM 7700 sequence detection system (Applied Biosystems, Foster City, CA). Primer/probe sets were designed using Primer Express software (Applied Biosystems) and gene sequences available from GenBank TM data base.…”

Section: Methodsmentioning

confidence: 99%

Oleoylethanolamide Stimulates Lipolysis by Activating the Nuclear Receptor Peroxisome Proliferator-activated Receptor α (PPAR-α)

Guzmán

Verme

et al. 2004

Journal of Biological Chemistry

306

283

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Amides of fatty acids with ethanolamine (FAE) are biologically active lipids that participate in a variety of biological functions, including the regulation of feeding. The polyunsaturated FAE anandamide (arachidonoylethanolamide) increases food intake by activating G proteincoupled cannabinoid receptors. On the other hand, the monounsaturated FAE oleoylethanolamide (OEA) reduces feeding and body weight gain by activating the nuclear receptor PPAR-␣ (peroxisome proliferator-activated receptor ␣). In the present report, we examined whether OEA can also influence energy utilization. OEA (1-20 M) stimulated glycerol and fatty acid release from freshly dissociated rat adipocytes in a concentration-dependent and structurally selective manner. Under the same conditions, OEA had no effect on glucose uptake or oxidation. OEA enhanced fatty acid oxidation in skeletal muscle strips, dissociated hepatocytes, and primary cardiomyocyte cultures. Administration of OEA in vivo (5 mg kg ؊1 , intraperitoneally) produced lipolysis in both rats and wild-type mice, but not in mice in which PPAR-␣ had been deleted by homologous recombination (PPAR-␣ ؊/؊ ). Likewise, OEA was unable to enhance lipolysis in adipocytes or stimulate fatty acid oxidation in skeletal muscle strips isolated from PPAR-␣ mice. The synthetic PPAR-␣ agonist Wy-14643 produced similar effects, which also were dependent on the presence of PPAR-␣. Subchronic treatment with OEA reduced body weight gain and triacylglycerol content in liver and adipose tissue of dietinduced obese rats and wild-type mice, but not in obese PPAR-␣ ؊/؊ mice. The results suggest that OEA stimulates fat utilization through activation of PPAR-␣ and that this effect may contribute to its anti-obesity actions.Amides of long-chain fatty acids with ethanolamine (FAE) 1 are a family of lipid mediators produced through the concerted action of two enzymes present in mammalian cells: N-acyltransferase, which transfers a fatty acid from the sn-1 position of a donor phospholipid to the free amine in phosphatidylethanolamine, producing N-acyl-phosphatidylethanolamine; and phospholipase D, which converts N-acyl-phosphatidylethanolamine to FAE (1, 2). The FAE are hydrolyzed intracellularly to fatty acids and ethanolamine by the action of fatty acid amide hydrolase enzymes (3)(4)(5).Although the FAE were first described four decades ago (6), they did not attract much attention until the discovery that a polyunsaturated member of this family, anandamide (arachidonoylethanolamide), is an endogenous ligand for cannabinoid receptors, G protein-coupled receptors targeted by the marijuana constituent ⌬ 9 -tetrahydrocannabinol (7). Anandamide is now established as a brain endocannabinoid messenger (8) and multiple roles for other FAE have also been proposed (9 -11). One emerging function of these lipid mediators is the regulation of feeding behavior. Anandamide causes overeating in rats because of its ability to activate cannabinoid receptors (12). This action is of therapeutic relevance: cannabinoid agonists su...

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Opposite Effects of Insulin and Glucagon in Acute Hormonal Control of Hepatic Lipogenesis

Cited by 100 publications

References 0 publications

Effects of Insulin and Glucose on Very Low Density Lipoprotein Triglyceride Secretion by Cultured Rat Hepatocytes

Effects of Insulin and Glucose on Very Low Density Lipoprotein Triglyceride Secretion by Cultured Rat Hepatocytes

Metabolic Effects of Water Deprivation

Oleoylethanolamide Stimulates Lipolysis by Activating the Nuclear Receptor Peroxisome Proliferator-activated Receptor α (PPAR-α)

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