Some Effects of Continued Protein Deprivation, with and without Methionine Supplementation, on Intracellular Liver Components.

Seifter, Sam; Müntwyler, Edward; Harkness, David M.

doi:10.3181/00379727-75-18095

Cited by 55 publications

(50 citation statements)

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“…Plasma insulin and glucagon were determined by enzymelinked immunosorbent assay (Alpco Diagnostics, Windham, NH) and radioimmunoassay (Linco, St. Charles, MO), respectively. Liver triglycerides and glycogen content were determined as previously described (33,34). Clinical chemistry analysis of plasma samples was performed at BTS (San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Fructose 1,6-Bisphosphatase Reduces Excessive Endogenous Glucose Production and Attenuates Hyperglycemia in Zucker Diabetic Fatty Rats

Poelje¹,

Potter²,

Chandramouli

et al. 2006

Diabetes

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Gluconeogenesis is increased in type 2 diabetes and contributes significantly to fasting and postprandial hyperglycemia. We recently reported the discovery of the first potent and selective inhibitors of fructose 1,6-bisphosphatase (FBPase), a rate-controlling enzyme of gluconeogenesis. Herein we describe acute and chronic effects of the lead inhibitor, MB06322 (CS-917), in rodent models of type 2 diabetes. In fasting male ZDF rats with overt diabetes, a single dose of MB06322 inhibited gluconeogenesis by 70% and overall endogenous glucose production by 46%, leading to a reduction in blood glucose of >200 mg/dl. Chronic treatment of freely feeding 6-week-old male Zucker diabetic fatty (ZDF) rats delayed the development of hyperglycemia and preserved pancreatic function. Elevation of lactate (ϳ1.5-fold) occurred after 4 weeks of treatment, as did the apparent shunting of precursors into triglycerides. Profound glucose lowering (ϳ44%) and similar metabolic ramifications were associated with 2-week intervention therapy of 10-week-old male ZDF rats. In high-fat diet-fed female ZDF rats, MB06322 treatment for 2 weeks fully attenuated hyperglycemia without evidence of metabolic perturbation other than a modest reduction in glycogen stores (ϳ20%). The studies confirm that excessive gluconeogenesis plays an integral role in the pathophysiology of type 2 diabetes and suggest that FBPase inhibitors may provide a future treatment option.

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Section: Methodsmentioning

confidence: 99%

Inhibition of Fructose 1,6-Bisphosphatase Reduces Excessive Endogenous Glucose Production and Attenuates Hyperglycemia in Zucker Diabetic Fatty Rats

Poelje¹,

Potter²,

Chandramouli

et al. 2006

Diabetes

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show abstract

“…The technique used to isolate the glycogen was a modification of the technique described by Moody and Felber [38]. Glycogen was further purified by a second precipitation with 950/, ethanol, and, after dissolution in water, aliquots were analyzed for radioactivity by scintillation counting and for glycogen by the anthrone method [39]. The radioactivity was assayed in a Mark I liquid scintillation counter (Nuclear, Chicago) with a liquid scintillation mixture containing PPO, POPOP in ethanol and toluol (1.2 :2, v/v).…”

Section: Methodsmentioning

confidence: 99%

Studies on the Metabolic Effects Induced in the Rat by a High‐Fat Diet

Bringolf¹,

Zaragoza²,

Rivier³

et al. 1972

European Journal of Biochemistry

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I . Rats were fed from weaning during 3-4 weeks a high fat carbohydrate-poor diet.Control groups received a diet in which fat was completely replaced by starch in the same caloric proportion.2. The effect of this high-fat diet on the metabolism of pyruvate in diaphragm in vitro was investigated. Glycogen breakdown and glyceride content of the tissue were also measured.3. Fat diet was shown to induce a reduction in 14C0, production from labelled pyruvate and in the pyruvate uptake. Acetate oxidation was found to be unchanged after fat feeding. This gives evidence for an inhibition of the pyruvate dehydrogenase reaction in diaphragm from fatfed rats.4. The breakdown of glycogen during either an incubation in vitro or a 24-h fast was significantly reduced in diaphragm from fat-fed rats.5. Diaphragm glycerides were found to be increased four-fold by fat diet. Examination by light-microscopy of muscle sections have shown that glycerides were present in the muscle fibre and not in adipose tissue cells in the preparation.6. Inhibition of the oxidation of fatty acids by 2-bromostearate was shown t o reverse completely the impairment of pyruvate metabolism and to stimulate glycolysis. I n diaphragm from carbohydrate-fed rats 2-bromostearate induced no significant effect on carbohydrate metabolism. Similar results were obtained with glucose as substrate.7. Rats were fed the high-fat diet and then the high-carbohydrate one for a few days. This change of diet was shown to induce a rapid reversal of the inhibition of glucose oxidation in diaphragm in vitro.8. These results indicate that the impairment of carbohydrate metabolism in diaphragm from fat-fed rats is probably due to an increased oxidation of fatty acids as observed in muscle from alloxan-diabetic or starved rats rather than to enzymatic adaptations.An impairment in the metabolism of pyruvate in vivo has been demonstrated in human diabetes either by an intravenous pyruvate tolerance test [ 11 or by measuring blood-pyruvate levels during a glucose-insulin test [2,3]. It was also occasionally observed with the same methods in human obesity [4,5]. Such an impairment has been shown also in normal dog treated with lipolytic hormones or infused with free fatty acids before an intravenous glucose load [6], in alloxan-diabetic non-obese mice and in genetically obese mice by determination of expired 14C02 after injection of [14C]pyruvate to the animal [7].In vitro, the uptake and the oxidation of pyruvate have been found to be impaired in the muscle from alloxan-diabetic rats [8-

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“…Nitrogen was determined by a micro Kjeldahl method [6]. Total neutral hexose was assayed with the anthrone reagent [3] using galactose as standard and correcting for the different molar absorption produced by fucose under these conditions. Fucose was determined by the method of Gibbons [7].…”

Section: Analvtica1 Methodsmentioning

confidence: 99%

“…Fractions (3.8 ml) were collected at 20 ml/h and the absorbance of these measured at 280 nm. Total hexose of aliquots (0.5 ml) from alternate tubes were measured using anthrone [3].…”

Section: Fractionation Of Sputummentioning

confidence: 99%

Isolation and Characterisation of Glycoproteins from Sputum

Roberts

1974

European Journal of Biochemistry

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Sputum has been separated into a sol and a gel phase by ultracentrifugation and the components of these phases examined. A glycoprotein of high molecular weight as well as serum albumin, immunoglobulin A, sll acid glycoprotein and lactoferrin were detected in the sol phase by gel filtration and immunodiffusion studies. A glycoprotein of similar chemical composition was isolated from the gel phase by solubilisation in 6 M urea/O. 1 M NaCl followed by fractional precipitation with ethanol.The carbohydrate content of this glycoprotein, termed the bronchial glycoprotein, varied from 58 (w/w) to 69% (w/w) with sputum from different patients and was composed of fucose, galactose, galactosamine, glucosamine and N-acetylneuraminic acid. Serine, threonine and proline constituted 44% (w/w) of the amino acid residues of the bronchial glycoprotein and an alkaline borohydride cleavage study indicated that 0-glycosidic linkages exist between N-acetylgalactosamine and the hydroxyamino acids in the peptide core. Fractionation of the bronchial glycoprotein on DEAESephadex A-25 yielded fractions enriched in sulphate and sialic acid but separate fuco, sialo and sulpho glycoproteins were not obtained. Similarly fractionation of the oligosaccharides released by the action of alkaline borohydride yielded a complex mixture of oligosaccharides but sulphated oligosaccharides free of sialic acid were not obtained. Separation of the oligosaccharides into two fractions of different sizes showed that sulphate content was greatest in the larger oligosaccharides whereas sialic acid content was highest in the smaller oligosaccharides. A methylation study of the bronchial glycoprotein, neuraminidase-digested bronchial glycoprotein and mild acid-hydrolysed bronchial glycoprotein revealed that the N-acetylneuraminic acid was linked to C-3 of penultimate galactose units. Fucose occurs in three different linkages, approximately 50 % is linked to C-2 of penultimate galactose units, approximately 25 % is linked to C-4 of glucosamine residues already substituted at

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Some Effects of Continued Protein Deprivation, with and without Methionine Supplementation, on Intracellular Liver Components.

Cited by 55 publications

References 0 publications

Inhibition of Fructose 1,6-Bisphosphatase Reduces Excessive Endogenous Glucose Production and Attenuates Hyperglycemia in Zucker Diabetic Fatty Rats

Inhibition of Fructose 1,6-Bisphosphatase Reduces Excessive Endogenous Glucose Production and Attenuates Hyperglycemia in Zucker Diabetic Fatty Rats

Studies on the Metabolic Effects Induced in the Rat by a High‐Fat Diet

Isolation and Characterisation of Glycoproteins from Sputum

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