Effects of glucagon and insulin on fatty acid synthesis and glycogen degradation in the perfused liver of normal and genetically obese (<i>ob/ob</i>) mice

Y, G; Gove, Christopher D.; Hems, Douglas A.

doi:10.1042/bj1740761

Cited by 26 publications

(9 citation statements)

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“…28 Furthermore, the activity of acetyl-CoA carboxylase is stimulated or depressed after incubation of rat liver cells with insulin and glucagon, respectively. 46 -51154 - 55 ' 66 In apparent contrast to the latter finding are the studies of Cook et al, 49 Ma et al, 56 and Watkins et al, 48 who did not observe a diminished activity of acetyl-CoA carboxylase after glucagon treatment. Differences in the technique of homogenate preparation and in the assay for acetyl-CoA carboxylase activity may explain this disparity.…”

Section: Hormonal Regulation Of Fatty Acid Synthesismentioning

confidence: 62%

“…Insulin stimulates cholesterol synthesis in several lines of cultured mammalian cells 289 and freshly isolated rat liver cells. 43 -45 -290 Glucagon inhibits cholesterogenesis in perfused mouse liver 56 and in isolated hepatocytes, 43 -45 -290 -292 although some observers have claimed otherwise. 49 -292 Glucagon also blocks the increase in cholesterol synthesis caused by insulin in isolated hepatocytes.…”

Section: Hormonal Regulation Of Cholesterol Synthesismentioning

confidence: 95%

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Short-term Hormonal Control of Hepatic Lipogenesis

et al. 1980

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L ipids are essential components of all living cells, functioning as an energy store and playing an important role in all biologic membranes. Triacylglycerols, the storage form and most abundant of the glycerolipids, represent a highly concentrated form of energy, yielding twice as many calories per gram as carbohydrate or protein. The phospholipids are amphipathic compounds which, along with cholesterol, are found in membranes where they interact to provide a polar-faced, hydrophobic continuum of critical importance for proper cell structure and function.A major function of lipogenesis is to store (as triacylglycerols) the chemical energy or foodstuffs ingested above the immediate requirements of an organism. Contrary to protein, which is not stored, and to carbohydrate, which can only be stored in limited quantities, the capacity to store triacylglycerols is almost unlimited. The ability to keep large amounts of triacylglycerols on board would not be useful, however, if it were not possible to quickly and efficiently stop diverting foodstuffs into triacylglycerol formation and to quickly and efficiently start utilizing these compounds to provide the energy necessary to synthesize ATP. For this reason, mechanisms have evolved which finely tune the synthesis and degradation of triacylglycerol to the ever changing demand for ATP. In contrast, phospholipid and cholesterol synthesis must be, at least, partially maintained (or their degradation curtailed), even in the face of limited food intake or frank starvation, to provide sufficient quantities of these lipids to fulfill their crucial role in biologic membranes.In rodents the proportion of total body fatty acids synthesized by the liver ranges from 3% (fasted animals) to 50% (in animals force fed with glucose). 1 ' 2 Even greater percentages are synthesized in the human 3 and avian 4 liver. Dietary control of lipogenesis is more pronounced and more prompt in the liver than in any other tissue, further emphasizing the fact that the liver is of considerable importance as a lipogenic organ. 1 The rate of lipogenesis in mammalian liver is regulated by two types of mechanisms, distinguished by the time required for them to take effect. One involves long-term, adaptive changes in enzyme activity, due to fluctuations in the absolute amounts of the key lipogenic enzymes. 5 " 10 This type of regulation is subject to hormonal and nutritional factors and takes a few hours to come into effect. The other involves short-term mechanisms, which operate on a minute to minute basis. The latter, involving modulation of enzymatic activity by substrate supply, allosteric effectors, and interconversion of enzymes between active and inactive forms by a phosphorylation cycle, has not received as much attention as have the long-term adaptive changes of the lipogenic enzymes and is not as well understood as a means of regulating lipogenesis. In this review, we will focus attention on conditions and factors, e.g., hormones, that bring about rapid changes in the rate of hepatic lipogenesis;...

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Section: Hormonal Regulation Of Fatty Acid Synthesismentioning

confidence: 62%

Section: Hormonal Regulation Of Cholesterol Synthesismentioning

confidence: 95%

Short-term Hormonal Control of Hepatic Lipogenesis

et al. 1980

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“…Early studies [14,50] suggested that insulin's direct action on hepatic GNG was important for controlling hepatic glucose production. Other studies revealed a correlation between insulin action on the peripheral tissue and substrate supply for hepatic GNG [12], and suggested that insulin's direct effect on the liver was to inhibit GLY [13] rather than GNG.…”

Section: Effects Of Insulin On Metabolism In the Isolated Perfused Momentioning

confidence: 99%

Effects of insulin and cytosolic redox state on glucose production pathways in the isolated perfused mouse liver measured by integrated 2H and 13C NMR

Hausler

Browning

Merritt

et al. 2006

Biochemical Journal

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A great deal is known about hepatic glucose production and its response to a variety of factors such as redox state, substrate supply and hormonal control, but the effects of these parameters on the flux through biochemical pathways which integrate to control glucose production are less clear. A combination of 13 C and [ 2 H]water tracers and NMR isotopomer analysis were used to investigate metabolic fluxes in response to altered cytosolic redox state and insulin. In livers isolated from fed mice and perfused with a mixture of substrates including lactate/pyruvate (10:1, w/w), hepatic glucose production had substantial contributions from glycogen, PEP (phosphoenolpyruvate) and glycerol. Inversion of the lactate/pyruvate ratio (1:10, w/w) resulted in a surprising decrease in the contribution from glycogen and an increase in that from PEP to glucose production. A change in the lactate/pyruvate ratio from 10:1 to 1:10 also stimulated flux through the tricarboxylic acid cycle (2-fold), while leaving oxygen consumption and overall glucose output unchanged. When lactate and pyruvate were eliminated from the perfusion medium, both gluconeogenesis and tricarboxylic-acid-cycle flux were dramatically lower. Insulin lowered glucose production by inhibiting glycogenolysis at both low and high doses, but only at high levels of insulin did gluconeogenesis or tricarboxylic-acid-cycle flux tend towards lower values (P < 0.1). Our data demonstrate that, in the isolated mouse liver, substrate availability and cellular redox state have a dramatic impact on liver metabolism in both the tricarboxylic acid cycle and gluconeogenesis. The tight correlation of these two pathways under multiple conditions suggest that interventions which increase or decrease hepatic tricarboxylic-acid-cycle flux will have a concomitant effect on gluconeogenesis and vice versa.

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“…The liver of genetically obese (oblob) mice exhibits resistance to the inhibitory action of vasopressin and glucagon on fatty acid synthesis, although the hormones stimulate glycogenolysis normally (Hems & Ma, 1976;Ma et al, 1978). Resistance to vasopressin action persists even after severe starvation of the obese animals, so this characteristic may offer a clue about the nature of the inborn defect (Hems & Ma, 1976, 1979a.…”

Section: Introductionmentioning

confidence: 97%

“…The synthesis of fatty acids in the liver can be inhibited by several hormones (for review, see Hems, 1977Hems, , 1979b. Glucagon can inhibit fatty acid synthesis in the liver of the rat (Harris, 1975) or mouse (Muller, Singh, Orci & Jeanrenaud, 1976), partly via depletion of preferred carbohydrate substances such as glycogen (Ma, Gove & Hems, 1978) and also via a decrease in availability of pyruvate (Harris, 1975), but not as a rapid primary effect on lipogenesis (Raskin, McGarry & Foster, 1974;Ma et al, 1978). Vasopressin can inhibit lipogenesis (Ma & Hems, 1975) more rapidly than can glucagon, and over the same concentration range as that which stimulates glycogen breakdown, suggesting that this hormone can exert a direct primary inhibitory effect on lipogenesis in liver (Ma & Hems, 1975).…”

Section: Introductionmentioning

confidence: 99%

Catabolic Effects of Adrenaline and Angiotensin II in the Perfused Liver of Normal and Genetically Obese (ob/ob) Mice

Gove

Cawthorne

et al. 1979

Clinical Science

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1. Rapid effects of hormones on the metabolism of glycogen and fatty acids were studied in the perfused liver of normal and genetically obese (ob/ob) mice. 2. In livers from normal and obese mice adrenaline and angiotensin II stimulated glycogenolysis. 3. These hormones inhibited the synthesis de novo of long-chain fatty acids in livers from normal mice, but not in livers from obese mice. 4. The proportion of acetyl-CoA carboxylase in the active form was decreased by adrenaline but not by angiotensin II in livers from obese mice. 5. The potency of hormone effects on liver suggests that they could occur in the intact animal. 6. The results add to the evidence that hepatic fatty acid synthesis in genetically obese (ob/ob) mice is irreversibly resistant to inhibition by a range of hormones. Such resistance could be of primary significance in the pathogenesis of the obesity.

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Effects of glucagon and insulin on fatty acid synthesis and glycogen degradation in the perfused liver of normal and genetically obese (ob/ob) mice

Cited by 26 publications

References 55 publications

Short-term Hormonal Control of Hepatic Lipogenesis

Short-term Hormonal Control of Hepatic Lipogenesis

Effects of insulin and cytosolic redox state on glucose production pathways in the isolated perfused mouse liver measured by integrated 2H and 13C NMR

Catabolic Effects of Adrenaline and Angiotensin II in the Perfused Liver of Normal and Genetically Obese (ob/ob) Mice

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