Suppression of Glycolysis Is Associated with an Increase in Glucose Cycling in Hepatocytes from Diabetic Rats

Henly, Debra C.; Phillips, John W.; Berry, Michael N.

doi:10.1074/jbc.271.19.11268

Cited by 26 publications

(26 citation statements)

References 35 publications

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“…Glycolysis was calculated as the sum of tritiated pyruvate, lactate, amino acids, and tritiated water in vials containing [6-3 H]glucose (24). Glucose cycling was calculated as the difference between glucose phosphorylation and total glucose metabolism (glycolysis ϩ [6-3 H]glucose incorporation into glycogen) (24). Thus glucose cycling represents phosphorylated glucose not further metabolized either glycolytically or into glycogen (24).…”

Section: Calculationsmentioning

confidence: 99%

“…Estimation of tritiated glycogen served to decrease the error resulting from incomplete equilibration between glucose 6-phosphate and fructose 6-phosphate (26). Glycolysis was calculated as the sum of tritiated pyruvate, lactate, amino acids, and tritiated water in vials containing [6-3 H]glucose (24). Glucose cycling was calculated as the difference between glucose phosphorylation and total glucose metabolism (glycolysis ϩ [6-3 H]glucose incorporation into glycogen) (24).…”

Section: Calculationsmentioning

confidence: 99%

“…Rates of glucose phosphorylation were calculated from the sum of accumulated 3 H2O and tritiated glycogen from vials containing [2-3 H]glucose (24). Estimation of tritiated glycogen served to decrease the error resulting from incomplete equilibration between glucose 6-phosphate and fructose 6-phosphate (26).…”

Section: Calculationsmentioning

confidence: 99%

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Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats

Commerford

Ferniza

Bizeau

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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High-fat (HFD) and high-sucrose diets (HSD) reduce insulin suppression of glucose production in vivo, increase the capacity for gluconeogenesis in vitro, and increase glucose-6-phosphatase (G-6-Pase) activity in whole cell homogenates. The present study examined the effects of HSD and HFD on in vivo gluconeogenesis, the catalytic and glucose-6-phosphate translocase subunits of G-6-Pase, glucokinase (GK) translocation, and glucose cycling. Rats were fed a high-starch control diet (STD; 68% cornstarch), HSD (68% sucrose), or HFD (45% fat) for 7-13 days. The ratio of 3 H in C6:C2 of glucose after 3 H2O injection into 6-to 8-h-fasted rats was significantly increased in HSD (0.68 Ϯ 0.07) and HFD (0.71 Ϯ 0.08) vs. STD (0.40 Ϯ 0.10). G-6-Pase activity was significantly higher in HSD and HFD vs. STD in both intact and disrupted liver microsomes. HSD and HFD significantly increased the amount of the p36 catalytic subunit protein, whereas the p46 glucose-6-phosphate translocase protein was increased in HSD only. Despite increased nonglycerol gluconeogenesis and increased G-6-Pase, basal glucose and insulin levels as well as glucose production were not significantly different among groups. Hepatocyte cell suspensions were used to ascertain whether diet-induced adaptations in glucose phosphorylation and GK might serve to compensate for upregulation of G-6-Pase. Tracer-estimated glucose phosphorylation and glucose cycling (glucose 7 glucose 6-phosphate) were significantly higher in cells isolated from HSD only. After incubation with either 5 or 20 mM glucose and no insulin, GK activity (nmol⅐mg protein Ϫ1 ⅐min Ϫ1) in digitonin-treated eluates (translocated GK) was significantly higher in HSD (32 Ϯ 4 and 146 Ϯ 6) vs. HFD (4 Ϯ 1 and 83 Ϯ 10) and STD (9 Ϯ 2 and 87 Ϯ 9). Thus short-term, chronic exposure to HSD and HFD increase in vivo gluconeogenesis and the G-6-Pase catalytic subunit. Exposure to HSD diet also leads to adaptations in glucose phosphorylation and GK translocation.glucose-6-phosphatase; liver; glucose metabolism; glucokinase IN VIVO ESTIMATES SUGGEST that some prediabetic states (31, 44) and type 2 diabetes (56, 64) are characterized by increased gluconeogenesis. Accelerated gluconeogenesis in both prediabetic states and type 2 diabetes likely results from many factors, including increased precursor delivery, alterations in the hormonal milieu, and intrahepatic adaptations that increase the conversion of precursors into glucose (56,64). In prediabetic states, increased gluconeogenesis does not result in the overproduction of glucose. This autoregulation of glucose production appears to involve reciprocal regulation of glycogenolysis (64). The development of fasting hyperglycemia and progression into type 2 diabetes likely involves an impairment in autoregulation of glucose production. Although pancreatic insufficiency would certainly contribute to the reduced ability to restrain basal glucose production in type 2 diabetes, intrahepatic adaptations such as reduced tyrosine kinase activity, increased phosphatidylin...

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Section: Calculationsmentioning

confidence: 99%

Section: Calculationsmentioning

confidence: 99%

See 1 more Smart Citation

Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats

Commerford

Ferniza

Bizeau

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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“…51 ATP concentrations were predicted to fall when simulating insulin resistance, particularly when combined with raised dietary lipid intake (Figure 3b), as is seen experimentally. [52][53][54][55][56] This was notably more severe in perivenous, than periportal cells. Disruptions to energy metabolism have been suggested as possible mechanisms for the progression of NAFLD to NASH.…”

Section: Inputs and Representing Nafld In The Modelmentioning

confidence: 92%

Liver function as an engineering system

et al. 2016

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Process Systems Engineering has tackled a wide range of problems including manufacturing, the environment, and advanced materials design. Here we discuss how tools can be deployed to tackle medical problems which involve complex chemical transformations and spatial phenomena looking in particular at the liver system, the body's chemical factory. We show how an existing model has been developed to model distributed behavior necessary to predict the behavior of drugs for treating liver disease. The model has been used to predict the effects of suppression of de novo lipogenesis, stimulation of b-oxidation and a combination of the two. A reduced model has also been used to explore the prediction of behavior of hormones in the blood stream controlling glucose levels to ensure that levels are kept within safe bounds using interval methods. The predictions are made resulting from uncertainty in two key parameters with oscillating input resulting from regular feeding. V C 2016 The Authors AIChE Journal published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers AIChE J, 62: 3285-3297, 2016 Keywords: mathematical modeling, biomedical engineering, systems biology, medical, controlThe liver, its regulation, and its diseases Why systems engineering of the liver?Systems Engineering is the discipline of the management of complex engineering systems over their whole life cycle. Process Systems Engineering is the study of complex process engineering systems involving chemical and physical change. Prof Roger Sargent was a pioneer from the 1950s in seeing the potential that computers could have to revolutionize the way that we tackled these problems.1 He also saw the way Chemical Engineering was broadening its base into molecular and biological systems to improve manufacturing. 1,2The liver is one part of a very complex processing system which ensures that all parts of the body receive the energy and nutrients that they need, that waste products are removed efficiently from the various streams, and that short and long term well being are maintained. It is the body's central chemical processing organ. Considering the liver system as one which controls chemical and physical change within the body, particularly of nutrition, makes it a legitimate area of study for Process Systems Engineers. A number of Chemical Engineers have also contributed to the use for Process Systems Engineering to a range of medical applications. Bogle 3 reviews recent

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“…The elevated G6P-ase activity and mRNA level [40] in animals in the diabetic state resulted in increased dephosphorylation of G6P and stimulation of endogenous glucose production [41], which is the main reason for hyperglycemia in all types of diabetes [42]. The increased G6P-ase activity in conditions of experimental diabetes is accompanied with increased activity of F1,6BP-ase.…”

Section: Discussionmentioning

confidence: 99%

Prior heat stress induces moderation of diabetic alterations in glycogen metabolism of rats

Miova

Dinevska-Ќovkarovska

Djimrevska³

et al. 2013

Open Life Sciences

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Adaptation to one environmental stressor sometimes provides protection against additional, more intensive type of stress, a phenomenon called cross-tolerance. We aimed to estimate theprotection provided by acute heat stress (AHS) over carbohydrate disturbances in streptozotocin-diabetic rats. We investigated changes in activity of some hepatic glycolitic and gluconeogenic enzymes, and concentration of some substrates in control and diabetic animals exposed to AHS (41±0.5°C / 1 h), with 1 h and 24 h recovery at room temperature before sacrifice or induction of streptozotocin (STZ)-diabetes, respectively. AHS with 1 h-recovery before sacrifice resulted in intensive glycogenolysis, directed to endogenous glucose production and further utilization of glucose by peripheral tissues, while 24 h recovery resulted in a slight tendency towards normalization of metabolic disturbances caused by AHS. Experimental diabetes caused a significant decrease of substrates and glycolytic enzymes, but an increase of gluconeogenic enzymes. In diabetic animals previously exposed to AHS we measured a less intensive decrease of liver glycogen and glucose-6-phosphate concentration and hexokinase activity, as well as less intensive increase of liver glucose concentration, glucose-6-phosphatase and fructose-1,6-bisphosphatase activity compared to control diabetic animals that had been maintained at room temperature. Prior AHS provided some protection over diabetes-induced alterations in carbohydrate-related parameters (see graphical apstract), indicating a possible development of cross-tolerance phenomenon between the two stressors, AHS and STZ-diabetes.

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Suppression of Glycolysis Is Associated with an Increase in Glucose Cycling in Hepatocytes from Diabetic Rats

Cited by 26 publications

References 35 publications

Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats

Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats

Liver function as an engineering system

Prior heat stress induces moderation of diabetic alterations in glycogen metabolism of rats

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