Alloxan Diabetes and Demonstrated Direct Action of Insulin on Metabolism of Isolated Perfused Rat Liver

1957 ◽  
Vol 192 (1) ◽  
pp. 33-42 ◽  
Author(s):  
David E. Haft ◽  
Leon L. Miller
Keyword(s):  
Alloxan Diabetes ◽  
Direct Action ◽  
Operative Procedure ◽  
Diabetic Rats ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Insulin Administration ◽  
Positive Effects ◽  
Per Se ◽  
Partial Correction

The direct effect of insulin was studied in intact surviving livers removed from normal and alloxan-diabetic rats and perfused for 4 hours with rat blood containing acetate-1-C14. Changes due to diabetes per se were a) decreased lipogenesis from acetate, b) increased ureogenesis, and c) increased incorporation of acetate into carbohydrate. The positive effects of insulin consisted of an at least partial correction of the depressed lipogenesis characteristic of diabetes and of fasting, and a net removal of glucose from the perfusate after the 1st hour. The action of insulin was inhibited in most of the experiments with ketotic liver donors, and also in many experiments in which the operative procedure was accompanied by excessive trauma. Insulin administration depressed gluconeogenesis from acetate and lowered ketogenesis in experiments with alloxan diabetic donors.

Regulation of hepatic triiodothyronine production in the streptozotocin-induced diabetic rat

1984 ◽  
Vol 247 (4) ◽  
pp. E526-E533
Author(s):  
A. S. Jennings
Keyword(s):  
Diabetic Rats ◽  
Diabetic Rat ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Insulin Administration ◽  
Progressive Decline ◽  
Serum T4 ◽  
Fasted Rats

The effect of diabetes on 3,5,3'-triiodothyronine (T3) production was determined in the isolated perfused rat liver. Induction of diabetes with streptozotocin resulted in decreased serum thyroxine (T4) and T3 levels and a progressive decline in hepatic T3 production over 5 days. The decline in T3 production resulted from decreased conversion of T4 to T3, whereas T4 uptake was unchanged. Insulin administration restored serum T4 and T3, hepatic conversion of T4 to T3, and T3 production to normal levels. When serum T4 levels in diabetic rats were maintained by T4 administration, the conversion of T4 to T3 and T3 production returned to control levels. However, restoration of serum T4 levels in fasted rats failed to correct the decrease in hepatic T4 uptake or T3 production. Glucagon, at supraphysiological concentrations in vitro and in vivo, slightly decreased T4 uptake and T3 production without altering the conversion of T4 to T3. These data suggest that the fall in serum T4 levels observed in diabetic rats is important in mediating the decreased hepatic conversion of T4 to T3 and T3 production.

scholarly journals Rates of ketone-body formation in the perfused rat liver

1969 ◽  
Vol 112 (5) ◽  
pp. 595-600 ◽  
Author(s):  
H. A. Krebs ◽  
Patricia G. Wallace ◽  
R. Hems ◽  
R. A. Freedland
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Ketone Bodies ◽  
Short Chain Fatty Acids ◽  
Diabetic Rats ◽  
Isolated Perfused Rat Liver ◽  
Perfused Liver ◽  
Perfused Rat Liver ◽  
Normal Range ◽  
Physiological Value

1. The rates of formation of acetoacetate and β-hydroxybutyrate by the isolated perfused rat liver were measured under various conditions. 2. The rates found after addition of butyrate, octanoate, oleate and linoleate were about 100μmoles/hr./g. wet wt. in the liver of starved rats. These rates are much higher than those found with rat liver slices. 3. The differences between the rates given by slices and by the perfused organ were much higher with the long-chain than with short-chain fatty acids. The increments caused by oleate and linoleate were 12 and 16 times as large in the perfused organ as in the slices, whereas the increments caused by butyrate and octanoate were about four times as large. 4. The rates of ketogenesis in the unsupplemented perfused liver of well-fed rats, and the increments caused by the addition of fatty acids, were about half of those in the liver from starved rats. 5. The value of the [β-hydroxybutyrate]/[acetoacetate] ratio of the medium was raised by octanoate, oleate and linoleate. 6. Carnitine did not significantly accelerate ketogenesis from fatty acids. 7. Oleate formed up to 82% of the expected yield of ketone bodies. 8. In the liver of alloxan-diabetic rats the endogenous rates of ketogenesis were raised, in some cases as high as in the liver from starved rats, after addition of oleate. 9. On addition of either β-hydroxybutyrate or acetoacetate to the perfusion medium the liver gradually adjusted the [β-hydroxybutyrate]/[acetoacetate] ratio towards the normal range. 10. The [β-hydroxybutyrate]/[acetoacetate] ratio of the medium was about 0·4 when slices were incubated, but near the physiological value of 2 when the liver was perfused. 11. The experiments demonstrate that for the study of ketogenesis slices are in many ways grossly inferior to the perfused liver.

Enhanced Sugar Uptake Fails to Simulate the Insulin Effect on Lipogenesis in the Isolated Perfused Rat Liver

1958 ◽  
Vol 193 (3) ◽  
pp. 469-475 ◽  
Author(s):  
David E. Haft ◽  
Leon L. Miller
Keyword(s):  
Metabolic Pathways ◽  
Ketone Body ◽  
Diabetic Rats ◽  
Sugar Uptake ◽  
Isolated Perfused Rat Liver ◽  
Primary Role ◽  
Perfused Rat Liver ◽  
Insulin Effect ◽  
Primary Action

Large quantities of glucose and fructose were infused without insulin into isolated livers of fasted normal and fed diabetic rats as a test of the widely accepted theory that the single primary role of insulin is to speed the entry of glucose into the cell. The liver disposed of large quantities of hexose in most cases without simultaneously increasing, as with insulin, the rate of incorporation of acetate-1-C14 into fatty acids. Much of the sugar was transformed to glycogen and CO2 without entering the pathways of fatty acid or ketone body synthesis, or influencing the conversion of acetate to these products. With livers of fasted normal rats, massive fructose infusion significantly inhibited urea formation and reduced the incorporation of acetate into glucose and plasma protein. The dissociation between carbohydrate balance and lipogenesis suggests that insulin has some primary action other than making more sugar available in metabolism. It is suggested that there is an anatomic separation of metabolic pathways in the liver, and that insulin serves to facilitate glucose transport between them.

Relationship between choline-deficient fatty liver and chronic alloxan diabetes in rats

1960 ◽  
Vol 198 (3) ◽  
pp. 637-639
Author(s):  
A. M. Cohen
Keyword(s):  
Fatty Acid ◽  
Alloxan Diabetes ◽  
Fatty Infiltration ◽  
Acid Synthesis ◽  
Diabetic Rats ◽  
Insulin Administration ◽  
Choline Deficiency ◽  
Deficient Diet ◽  
Diabetic State ◽  
Hepatic Fat

Choline deficiency in chronic alloxan-diabetic rats resulted in deterioration of the diabetic state. In alloxan-diabetic rats fed a choline-deficient diet the fatty infiltration of the liver was less than in nondiabetic rats on the same diet. Insulin administered to alloxan-diabetic and nondiabetic, choline-deficient rats further decreased the hepatic fat content and improved the diabetic state in the former. Administration of insulin during life caused a marked increase of fatty-acid synthesis in liver slices from both choline-fed and choline-deficient, alloxan-diabetic rats. Substituting fructose for starch in the choline-deficient diet failed to increase the hepatic fat of the diabetic or the nondiabetic animals. The decrease in hepatic fat following insulin administration to choline-deficient, alloxan-diabetic rats is apparently due to an extrahepatic effect of insulin, for it occurs in spite of the increased synthesis of fat in the liver induced by insulin.

Effects of fasting and alloxan diabetes on albumin synthesis by perfused rat liver

1961 ◽  
Vol 201 (1) ◽  
pp. 55-57 ◽  
Author(s):  
Julian B. Marsh
Keyword(s):  
Cell Suspension ◽  
Rat Liver ◽  
Alloxan Diabetes ◽  
Diabetic Rats ◽  
Red Cell ◽  
Perfused Rat Liver ◽  
Albumin Synthesis ◽  
Plasma Albumin ◽  
Immunochemical Method

The net synthesis of plasma albumin by the rat liver perfused with a red cell suspension has been studied by a quantitative immunochemical method. Albumin synthesis was decreased by an average of 29% after a 24-hr fast in normal rats. It was also decreased by 41% in alloxan diabetic rats.

Effect of Sex, Fasting and Alloxan Diabetes on the Uptake of Neutral Fat by Isolated Perfused Rat Liver

1958 ◽  
Vol 195 (3) ◽  
pp. 673-677 ◽  
Author(s):  
Murray Heimberg ◽  
H. C. Meng ◽  
C. R. Park
Keyword(s):  
Rat Liver ◽  
Alloxan Diabetes ◽  
Hormonal Control ◽  
Female Rats ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Fluid ◽  
Fat Uptake ◽  
Isolated Liver

A method is described for measuring the uptake of neutral fat by the perfused rat liver in vitro. The rate of fat uptake by the isolated liver was influenced by the endocrine balance of the animal at the time the organ was removed. Livers from female rats had a significantly greater rate of fat uptake than livers from males. The rate was markedly increased by fasting and by alloxan diabetes. Insulin reduced the fat uptake of the diabetic liver when the hormone was administered to the animal, but was ineffective when added directly to the perfusion fluid. The results suggest that the rate of uptake of neutral fat by the liver is under direct hormonal control.

scholarly journals Beneficial Effect of Zinc on diabetes induced kidney damage and liver stress oxidative in rats

2017 ◽  
Vol 10 (1) ◽  
pp. 2050-2055 ◽  
Author(s):  
Samir Derouiche ◽  
Djermoune Manel ◽  
Abbas Kawther
Keyword(s):  
Oxidative Stress ◽  
Adverse Effect ◽  
Uric Acid ◽  
Wistar Rats ◽  
Alloxan Diabetes ◽  
Zinc Supplementation ◽  
Body Weight Gain ◽  
Diabetic Rats ◽  
Stress Oxidative ◽  
Partial Correction

The present study was designed to investigate the effects of Zn supplementation on kikney function and liver oxidative stress in Alloxan diabetic rats. Male albino Wistar rats were randomly divided into 4 groups (n=10): Control,  Non Diabetic + zinc, Diabetic and Diabetic + Zinc. Diabetes was induced by alloxan (150 mg/kg). Zinc (231 mg/kg feed) as ZnSO4 7H2O was added to the feed of the animals in the zinc groups for 21 days. Alloxan Diabetes caused a significant decrease in body weight gain, serum and tissue zinc, serum protein concentrations, liver GSH, GPx and GST activities .In contrast, it led to an augmentation in urea, creatinine, uric acid and MDA in rats. Zinc supplementation in the diet for diabetic rats ensured a partial correction of the previous parameters. In conclusion, this study indicated that zinc act as powerful antioxidants which may exercise adverse effect against severity and complication of diabetes.

A Comparison of Plasminogen Activators Derived from Rat Plasma, Primary Rat Hepatocytes and Isolated Perfused Rat Liver

1982 ◽  
Vol 47 (02) ◽  
pp. 166-172 ◽  
Author(s):  
Yoav Sharoni ◽  
Maria C Topal ◽  
Patricia R Tuttle ◽  
Henry Berger
Keyword(s):  
Rat Liver ◽  
Isoelectric Point ◽  
Rat Hepatocytes ◽  
Cell Types ◽  
Plasminogen Activators ◽  
Rat Plasma ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Molecular Weights ◽  
Physiological Relevance

SummaryOf the two cell types it was possible to culture from the dissociated rat liver, hepatocytes and Kupffer cells, only the former were fibrinolytically active. Rat hepatocytes during the first 24 hr in culture secreted two plasminogen activators with molecular weights identical to those found in rat plasma, an 80,000-dalton form (PA-80) and a 45,000-dalton form (PA-45). Partially purified preparations of plasminogen activators from both sources were subjected to isoelectric focusing (IEF) to compare characteristics further. There were three distinct peaks of PA-45 in each preparation with isoelectric points of 7.1, 7.2 and 7.4; all electrophoretic forms had the same low affinity to fibrin. PA-80 from both sources displayed similar IEF profiles with forms ranging from pH values of 7 to 8, all with the same high affinity to fibrin. The major form of PA-80 in the plasma preparation had an isoelectric point of 7.9 whereas that in the hepatocyte preparation had an isoelectric point of 7.6. The isolated perfused rat liver was also shown to produce both PA-80 and PA-45 emphasizing the physiological relevance of the findings with hepatocytes. It is concluded that in the rat hepatocytes contribute to the plasma profile with regard to the plasminogen activator content.

scholarly journals Wine-Derived Phenolic Metabolites in the Digestive and Brain Function

Beverages ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. 7 ◽  
Author(s):  
Irene Zorraquín-Peña ◽  
Adelaida Esteban-Fernández ◽  
Dolores González de Llano ◽  
Begoña Bartolomé ◽  
M. Moreno-Arribas
Keyword(s):  
Brain Function ◽  
Biological Fluids ◽  
Direct Action ◽  
Neuronal Response ◽  
Oral Microbiota ◽  
Phenolic Metabolites ◽  
Chemical Complexity ◽  
Positive Effects ◽  
Wine Polyphenols ◽  
Health Promoting

Wine, and specifically red wine, is a beverage with a great chemical complexity comprising a particular combination of phenolic compounds which are directly associated with its health-promoting properties. Wine polyphenols could induce changes in the composition of intestinal microbiota that would affect the production of physiologically active phenolic metabolites modifying the content and phenolic profile at the systemic level. In addition, in the human population, it seems that different “metabotypes”, or patterns of metabolizing wine polyphenols, exist, which would be reflected in the different biological fluids (i.e., plasma, urine and feces) and tissues of the human body. Moreover, wine polyphenols might change the composition of oral microbiota by an antimicrobial action and/or by inhibition of the adhesion of pathogens to oral cells, thus contributing to the maintenance of oral health. In turn, polyphenols and/or its metabolites could have a direct action on brain function, by positively affecting signaling routes involved in stress-induced neuronal response, as well as by preventing neuroticism-like disorders (i.e., anxiety and depression) through anti-inflammatory and epigenetic mechanisms. All of this would condition the positive effects on health derived from moderate wine consumption. This paper reviews all these topics, which are directly related with the effects of wine polyphenols at both digestive and brain level. Further progresses expected in the coming years in these fields are also discussed.

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