The Experts below are selected from a list of 159 Experts worldwide ranked by ideXlab platform
Sheila Collins - One of the best experts on this subject based on the ideXlab platform.
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p38 mitogen activated protein kinase plays a stimulatory role in hepatic Gluconeogenesis
Journal of Biological Chemistry, 2005Co-Authors: Qu Fan Collins, Thomas C Becker, Jacques Robidoux, Edgar G Lupo, Yan Xiong, Kiefer W Daniel, Lisa M Floering, Sheila CollinsAbstract:Abstract Hepatic Gluconeogenesis is essential for maintaining blood glucose levels during fasting and is the major contributor to postprandial and fasting hyperglycemia in diabetes. Gluconeogenesis is a classic cAMP/protein kinase A-dependent process initiated by glucagon, which is elevated in the blood during fasting and in diabetes. In this study, we have shown that p38 mitogen-activated protein kinase (p38) was activated in liver by fasting and in primary hepatocytes by glucagon or forskolin. Fasting plasma glucose levels were reduced upon blockade of p38 with either a chemical inhibitor or small interference RNA in mice. In examining the mechanism, inhibition of p38 suppressed Gluconeogenesis in liver, along with expression of key gluconeogenic genes, including phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Peroxisome proliferator-activated receptor γ coactivator 1α and cAMP-response element-binding protein have been shown to be important mediators of hepatic Gluconeogenesis. We have shown that inhibition of p38 prevented transcription of the PPARγ coactivator 1α gene as well as phosphorylation of cAMP-response element-binding protein. Together, our results from in vitro and in vivo studies define a model in which cAMP-dependent activation of genes involved in Gluconeogenesis is dependent upon the p38 pathway, thus adding a new player to our evolving understanding of this physiology.
Mark A Magnuson - One of the best experts on this subject based on the ideXlab platform.
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cytosolic phosphoenolpyruvate carboxykinase does not solely control the rate of hepatic Gluconeogenesis in the intact mouse liver
Cell Metabolism, 2007Co-Authors: Shawn C Burgess, Tian Teng He, Jill Lindner, Dean A Sherry, Craig R Malloy, Jeffrey D Browning, Mark A MagnusonAbstract:Summary When dietary carbohydrate is unavailable, glucose required to support metabolism in vital tissues is generated via Gluconeogenesis in the liver. Expression of phosphoenolpyruvate carboxykinase (PEPCK), commonly considered the control point for liver Gluconeogenesis, is normally regulated by circulating hormones to match systemic glucose demand. However, this regulation fails in diabetes. Because other molecular and metabolic factors can also influence Gluconeogenesis, the explicit role of PEPCK protein content in the control of Gluconeogenesis was unclear. In this study, metabolic control of liver Gluconeogenesis was quantified in groups of mice with varying PEPCK protein content. Surprisingly, livers with a 90% reduction in PEPCK content showed only a ∼40% reduction in gluconeogenic flux, indicating a lower than expected capacity for PEPCK protein content to control Gluconeogenesis. However, PEPCK flux correlated tightly with TCA cycle activity, suggesting that under some conditions in mice, PEPCK expression must coordinate with hepatic energy metabolism to control Gluconeogenesis.
Dean A Sherry - One of the best experts on this subject based on the ideXlab platform.
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cytosolic phosphoenolpyruvate carboxykinase does not solely control the rate of hepatic Gluconeogenesis in the intact mouse liver
Cell Metabolism, 2007Co-Authors: Shawn C Burgess, Tian Teng He, Jill Lindner, Dean A Sherry, Craig R Malloy, Jeffrey D Browning, Mark A MagnusonAbstract:Summary When dietary carbohydrate is unavailable, glucose required to support metabolism in vital tissues is generated via Gluconeogenesis in the liver. Expression of phosphoenolpyruvate carboxykinase (PEPCK), commonly considered the control point for liver Gluconeogenesis, is normally regulated by circulating hormones to match systemic glucose demand. However, this regulation fails in diabetes. Because other molecular and metabolic factors can also influence Gluconeogenesis, the explicit role of PEPCK protein content in the control of Gluconeogenesis was unclear. In this study, metabolic control of liver Gluconeogenesis was quantified in groups of mice with varying PEPCK protein content. Surprisingly, livers with a 90% reduction in PEPCK content showed only a ∼40% reduction in gluconeogenic flux, indicating a lower than expected capacity for PEPCK protein content to control Gluconeogenesis. However, PEPCK flux correlated tightly with TCA cycle activity, suggesting that under some conditions in mice, PEPCK expression must coordinate with hepatic energy metabolism to control Gluconeogenesis.
Stephanie T Chung - One of the best experts on this subject based on the ideXlab platform.
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measurements of Gluconeogenesis and glycogenolysis a methodological review
Diabetes, 2015Co-Authors: Stephanie T Chung, Shaji K Chacko, Agneta L Sunehag, Morey W HaymondAbstract:Gluconeogenesis is a complex metabolic process that involves multiple enzymatic steps regulated by myriad factors, including substrate concentrations, the redox state, activation and inhibition of specific enzyme steps, and hormonal modulation. At present, the most widely accepted technique to determine Gluconeogenesis is by measuring the incorporation of deuterium from the body water pool into newly formed glucose. However, several techniques using radioactive and stable-labeled isotopes have been used to quantitate the contribution and regulation of Gluconeogenesis in humans. Each method has its advantages, methodological assumptions, and set of propagated errors. In this review, we examine the strengths and weaknesses of the most commonly used stable isotopes methods to measure Gluconeogenesis in vivo. We discuss the advantages and limitations of each method and summarize the applicability of these measurements in understanding normal and pathophysiological conditions.
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increased Gluconeogenesis in youth with newly diagnosed type 2 diabetes
Diabetologia, 2015Co-Authors: Stephanie T Chung, Shaji K Chacko, Daniel S Hsia, Luisa M Rodriguez, Morey W HaymondAbstract:Aims/hypothesis The role of increased Gluconeogenesis as an important contributor to fasting hyperglycaemia at diabetes onset is not known. We evaluated the contribution of Gluconeogenesis and glycogenolysis to fasting hyperglycaemia in newly diagnosed youths with type 2 diabetes following an overnight fast.
Mary C Gannon - One of the best experts on this subject based on the ideXlab platform.
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regulation of hepatic glucose production and the role of Gluconeogenesis in humans is the rate of Gluconeogenesis constant
Diabetes-metabolism Research and Reviews, 2008Co-Authors: Frank Q Nuttall, Mary C GannonAbstract:We have been interested in the metabolic effects of ingested fuels, both in normal subjects and in people with type 2 diabetes. Recently, we have become interested in the regulation of glucose production and the regulation of Gluconeogenesis in particular. We are not aware of a recent comprehensive review of these topics. Therefore, we have reviewed the currently available literature. The pertinent papers obtained from a Medline search of the words Gluconeogenesis, glycogenolysis, hepatic glucose output, as well as papers from our personal files, form the basis of this review. In order to analyse the data, it also was necessary to review the relevant methodology used in determining Gluconeogenesis. Pathway diagrams have been included with this review in order to illustrate and highlight key aspects of the methodologies. Current data support the hypothesis that the rate of glucose appearance changes but the rate of Gluconeogenesis remains remarkably stable in widely varying metabolic conditions in people without diabetes. In people with diabetes, whether Gluconeogenesis remains unchanged is at present uncertain. Available data are very limited. The mechanism by which Gluconeogenesis remains relatively constant, even in the setting of excess substrates, is not known. One interesting speculation is that gluconeogenic substrates substitute for each other depending on availability. Thus, the overall rate is either unaffected or only modestly changed. This requires further confirmation.