The Etiology of Diabetic Acidosis

Mirsky, I. Arthur

doi:10.1001/jama.1942.02830090008002

Cited by 28 publications

(11 citation statements)

References 29 publications

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“…A similar relationship is seen in the newborn rat; during the suckling period hepatic ketone production is elevated while the tissue glycogen level is low, whereas the converse situation obtains shortly after weaning (35,36). These observations regarding the interrelationship between glycogen content and ketogenesis are reminiscent of much older studies in the literature (37,38) and raise the intriguing possibility that glycogen might play a direct role in the regulation of carnitine acyltransferase activity. On the other hand, the inverse correlation between the two parameters did not manifest itself during the course of perfusion of livers from fed animals with glucagon added directly to the medium.…”

Section: Methodssupporting

confidence: 65%

Hormonal control of ketogenesis. Rapid activation of hepatic ketogenic capacity in fed rats by anti-insulin serum and glucagon.

McGarry¹,

Wright²,

Foster³

1975

J. Clin. Invest.

218

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A B STR A CT The enhanced capacity for long-chain fatty acid oxidation and ketogenesis that develops in the rat liver between 6 and 9 h after the onset of starvation was shown to be inducible much more rapidly by administration of anti-insulin serum or glucagon to fed rats. After only 1 h of treatment with either agent, the liver had clearly switched from a "nonketogenic" to a "ketogenic" profile, as determined by rates of acetoacetate and 1-hydroxybutyrate production on perfusion with oleic acid. As was the case after starvation, the administration of insulin antibodies or glucagon resulted in depletion of hepatic glycogen stores and a proportional increase in the ability of the liver to oxidize long-chain fatty acids and (-)-octanoylcarnitine, suggesting that all three treatment schedules activated the carnitine acyltransferase system of enzymes. In contrast to anti-insulin serum, which produced marked elevations in plasma glucose, free fatty acid, and ketone body concentrations, glucagon treatment had little effect on any of these parameters, presumably due to enhanced insulin secretion after the initial stimulation of glycogenolysis. Thus, after treatment with glucagon alone, it was possible to obtain a "ketogenic" liver from a nonketotic animal. The results are consistent with the possibility that the activity of carnitine acyltransferase, and thus ketogenic capacity, is subject to bihormonal control through the relative blood concentrations of insulin and glucagon, as also appears to be the case with hepatic carbohydrate metabolism.

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Section: Methodssupporting

confidence: 65%

Hormonal control of ketogenesis. Rapid activation of hepatic ketogenic capacity in fed rats by anti-insulin serum and glucagon.

McGarry¹,

Wright²,

Foster³

1975

J. Clin. Invest.

218

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“…In fact, the reciprocal relationship between hepatic glycogen content and ketogenesis had been discussed at length by several early investigators in the fi eld (74)(75)(76)(77). From these studies and the later work of Weinhouse et al (78) and Lossow et al (40,41) there emerged in the mid 1950s the concept of the "carbohydrate sparing" of hepatic fatty acid oxidation.…”

Section: The Role Of Malonyl-coa In the Regulation Of Ketogenesismentioning

confidence: 99%

Regulation of Hepatic Fatty Acid Oxidation and Ketone Body Production

Jd¹,

Dw²

1980

Annu. Rev. Biochem.

1,382

734

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“…The mechanism for this activation is not understood, though elevation of liver carnitine levels appears to be one component of the control system (2). It has long been known that a reciprocal relationship exists between liver glycogen content and fatty acid oxidation (3,4), and we have shown that high carnitine concentrations are not sufficient to induce ketosis if hepatic glycogen content is high (5). An attractive hypothesis was that some factor related to hepatic carbohydrate metabolism served to suppress fatty acid oxidation in the fed state.…”

Section: Introductionmentioning

confidence: 96%

A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis.

McGarry¹,

Mannaerts²,

Foster³

1977

J. Clin. Invest.

692

402

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A B S T R A C T Studies on the oxidation of oleic and octanoic acids to ketone bodies were carried out in homogenates and in mitochondrial fractions of livers taken from fed and fasted rats. Malonyl-CoA inhibited ketogenesis from the former but not from the latter substrate. The site of inhibition appeared to be the carnitine acyltransferase I reaction. The effect was specific and easily reversible. Inhibitory concentrations were in the range of values obtained in livers from fed rats by others. It is proposed that malonylCoA functions as both precursor for fatty acid synthesis and suppressor of fatty acid oxidation. As such, it might be an important element in the carbohydrate-induced sparing of fatty acid oxidation.

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The Etiology of Diabetic Acidosis

Cited by 28 publications

References 29 publications

Hormonal control of ketogenesis. Rapid activation of hepatic ketogenic capacity in fed rats by anti-insulin serum and glucagon.

Hormonal control of ketogenesis. Rapid activation of hepatic ketogenic capacity in fed rats by anti-insulin serum and glucagon.

Regulation of Hepatic Fatty Acid Oxidation and Ketone Body Production

A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis.

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