Metabolism in Diabetic Coma Produced by Alloxan

Kaplan, Nathan O.; Franks, M; Friedgood, Charles E.

doi:10.1126/science.102.2653.447

Cited by 24 publications

(6 citation statements)

References 7 publications

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“…This effect of insulin on diabetic diaphragm incubated with diabetic serum failed to appear when the diaphragms ofseverely diabeticrats with acidosis were used. In these experiments the known resistance of comatose alioxan-diabetic rats to insulin (Kaplan, Franks & Friedgood, 1945) was corroborated in vitro. In buffered salt solutions, however, no significant difference existed between the synthesis of glycogen in normal and diabetic diaphragms.…”

Section: Synthesis Of Glycogen In Alloxan-diabetic Ratsmentioning

confidence: 64%

The in vitro synthesis of glycogen in the diaphragms of normal and alloxan-diabetic rats

Tuerkischer

Wertheimer

1948

Biochemical Journal

109

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showed that surviving rat diaphragm can synthesize glycogen from added glucose. The rate of this synthesis may be increased by addition of insulin in vitro. Following these findings the in vitro synthesis of glycogen from glucose as well as glycogenolysis by muscle were further investigated. It was proposed to examine (a) the influence of the composition of the medium, and especially the effect ofpotassium, on these reactions, (b) the influence of adrenaline, (c) the effect ofinsulin in normal animals, and (d) the synthesis of glycogen and glycogenolysis in diaphragms from alloxandiabetic rats.Cross & Holmes (1937) and Ostern, Herbert & Holmes (1939) found that liver slices can synthesize glycogen in vitro from added glucose. Hastings & Buchanan (1942) demonstrated that in rat-liver slices this synthesis takes place only in a potassiumrich, sodium-free medium, corresponding in ionic composition to intracellular fluid. In a medium resembling extracellular fluid no synthesis of glycogen takes place. Saxton & Miller (1944) showed that even under optimal conditions this synthesis of glycogen depends on the time interval which elapses between the death of the animal and the beginning of the experiment in vitro. On the basis of these experiments the synthesis of glycogen and glycogenolysis in rat-liver slices were studied in vitro, and were compared with the same processes in the diaphragm. EXPERIMENTAL Method8 Preparation of the diaphragm. Male albino rats of laboratory stock weighing 80-120 g. were used. The animals were anaesthetized with nembutal (pentobarbital) and bled. The diaphragm was quickly excised and two equal portions were weighed. In control experiments with both halves incubated under identical conditions, we observed the same deviations as were reported by Gemmill (1940). Dividing the diaphragm of older rats into three or more equal parts proved to be unreliable. Media for incubation. (a) Buffered 8alt 8olution8. The diaphragm samples were incubated according to Gemmill (1940) at 380 in a medium described by Gey & Gey (1936) and modified by Gemmill (1940). Its composition was: 0-7 % NaCl, 0-037 % KCI, 0-227 % NaHCO3, 0-017% CaC12, 0-015% Na2HPO4, and 0.003% KH2PO4 (all % w/v). This medium was similar to the solution described by Van Dyke & Hastings (1928), and resembled body fluid in its ionic composition. It is referred to here as 'extracellular solution'. In our experiments modifications of this solution by addition or removal of an ion were compensated for by corresponding changes in NaCl content. With a modification of this solution, containing only 0.74% NaCl, 0-015% Na2HP04 and 0003% NaH2PO4, we obtained optimal synthesis of glycogen by rat diaphragm in vitro. This solution is called 'phosphate buffered saline'. The glucose content of the media was usually 100 mg./100 ml., the concentration most favourable according to Hechter et al. (1941) for the demonstration of the insulin effect.(b) Serum. For 'normal serum' pooled human serum was generally used, its glucose content being adjusted to 100 ...

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Section: Synthesis Of Glycogen In Alloxan-diabetic Ratsmentioning

confidence: 64%

The in vitro synthesis of glycogen in the diaphragms of normal and alloxan-diabetic rats

Tuerkischer

Wertheimer

1948

Biochemical Journal

109

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“…In fact, alloxan-diabetic rats tend to maintain their liver glycogen reserves better during fasting than the normal rat (15). Only when the animal enters a stage of terminal acidosis does the glycogen level fall (16).…”

Section: Resultsmentioning

confidence: 99%

Changes in Liver Glycogen Studied by the Needle Aspiration Technic in Patients With Diabetic Ketosis. With a Method for the Estimation of Glycogen From Histologic Preparations 1

Bondy

Sheldon²,

Evans³

1949

J. Clin. Invest.

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“…T hese results are in agreement with earlie r ones of Kaplan et at. (247), and indicate a marked derangeme n: t of phosphate metabolism in diabetic liver.…”

Section: The Action Of Insulinmentioning

confidence: 95%

“…The high liver glycogen is explained on the basis of the hypertrophy of the adrenal cortex in alloxan treated animals. In severely alloxan diabetic animals, Kaplan et al (247) have shown that fasting liver glycogen values are below those of fasted controls.…”

Section: Diabetogenic Chemicalsmentioning

confidence: 98%

Carbohydrate Metabolism

Colowick¹,

Kaplan²

1951

Annu. Rev. Biochem.

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The major developments during the past year have been along the fol1ow ing lines: (a) A renewal of interest in several alternate metabolic pathways, including the Warburg-Lipmann-Dickens pathway for glucose oxidation, via pentose, the Thunberg mechanism for formation of 4-carbon acids by con densation of two 2-carbon units, and the methyl glyoxalase system. (b) The establishment of the structure of two new coenzymes, one concerned in the galactose-glucose transformation, and the other, coenzyme A, concerned in the transfer of acyl groups. Acety!coenzyme A appears to be the long-sought "active acetate." (c) The development of the concept that dehydrogenases can participate in electron transfer, without dissociation of the "bound" pyridine nucleotides. (d) Advances in the understanding of the mechanism of heterotrophic and photosynthetic carbon dioxide assimilation. (e) Solubili zation and purification of certain enzymes of the citric acid cycle, which have heretofore been available only in particulate form. REVERSIBLE DEGRADATION OF CARBOHYDRATESTO 3-CARBON ACID STAGE THE OVER-ALL PROCESSAlternate pathways ' of degradation.-The term "glycolysis," usually ap plied to this process, is avoided here, because it is planned to consider in this section not only the reactions of the Embden-Meyerhof (E-M) scheme, but also the reactions of the Warburg-Lipmann-Dickens (W-L-D) scheme, which leads to the formation of triose by an alternate pathway. The former path way is usually regarded as anaerobic, and the latter as aerobic. A selective effect of a given inhibitor (e.g., iodoacetate or fluoride) on anaerobic metabo lism, without a corresponding depression of glucose oxidation, has been in terpreted as supporting the existence of two pathways for degradation of hexoses. More direct evidence for the occurrence of the W-L-D scheme in both animal and plant cells is described in a later section.The relative quantitative importance of these two pathways for glucose oxidation remains to be assessed. It may be worthy of note that whereas the E-M scheme provides, per molecule of hexose, two three-carbon fragmen ts 1 This review covers the period'from January 1st to December 31st, 1950.2 The foJlowing abbreviations are used throughout: ATP, ADP, and AMP for adenosinetri-, di-, and mono-phosphate; DPN and TPN for di-and triphosphopyri dine nucleotides; FAD for flavine adenine dinucleotide; P for phosphate, and ",P for energy-rich phosphate.'

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Metabolism in Diabetic Coma Produced by Alloxan

Cited by 24 publications

References 7 publications

The in vitro synthesis of glycogen in the diaphragms of normal and alloxan-diabetic rats

The in vitro synthesis of glycogen in the diaphragms of normal and alloxan-diabetic rats

Changes in Liver Glycogen Studied by the Needle Aspiration Technic in Patients With Diabetic Ketosis. With a Method for the Estimation of Glycogen From Histologic Preparations 1

Carbohydrate Metabolism

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