The role of protein translocation in the regulation of glycogen metabolism

Jurczak, Michael J.; Danos, Arpad; Rehrmann, Victoria R.; Brady, Matthew J.

doi:10.1002/jcb.21634

Cited by 17 publications

(15 citation statements)

References 71 publications

(77 reference statements)

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“…157 ) In addition, this process might involve the dephosphorylation of GYS2 by protein phosphatase 1 (PP1), which involves targeting subunits of PP1, especially G L (REF. 158 ) (FIG. 2b).…”

Section: Control Of Hepatic Glycogen Metabolismmentioning

confidence: 99%

Regulation of hepatic glucose metabolism in health and disease

2017

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The liver is crucial for the maintenance of normal glucose homeostasis — it produces glucose during fasting and stores glucose postprandially. However, these hepatic processes are dysregulated in type 1 and type 2 diabetes mellitus, and this imbalance contributes to hyperglycaemia in the fasted and postprandial states. Net hepatic glucose production is the summation of glucose fluxes from gluconeogenesis, glycogenolysis, glycogen synthesis, glycolysis and other pathways. In this Review, we discuss the in vivo regulation of these hepatic glucose fluxes. In particular, we highlight the importance of indirect (extrahepatic) control of hepatic gluconeogenesis and direct (hepatic) control of hepatic glycogen metabolism. We also propose a mechanism for the progression of subclinical hepatic insulin resistance to overt fasting hyperglycaemia in type 2 diabetes mellitus. Insights into the control of hepatic gluconeogenesis by metformin and insulin and into the role of lipid-induced hepatic insulin resistance in modifying gluconeogenic and net hepatic glycogen synthetic flux are also discussed. Finally, we consider the therapeutic potential of strategies that target hepatosteatosis, hyperglucagonaemia and adipose lipolysis.

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“…157 ) In addition, this process might involve the dephosphorylation of GYS2 by protein phosphatase 1 (PP1), which involves targeting subunits of PP1, especially G L (REF. 158 ) (FIG. 2b).…”

Section: Control Of Hepatic Glycogen Metabolismmentioning

confidence: 99%

Regulation of hepatic glucose metabolism in health and disease

2017

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“…Glucose is both taken up and released in the bloodstream from the liver (Jurczak et al, 2007). In liver hepatocytes, glucose enters and exits the cell through a bidirectional transporter: GLUT2.…”

Section: Effect Of Glucose On Transcriptional Regulationsmentioning

confidence: 99%

Transcriptional Regulation of Hepatic Fatty Acid Metabolism

Guillou¹,

Martin²,

Pineau³

2008

Subcellular Biochemistry

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The liver is a major site of fatty acid synthesis and degradation. Transcriptional regulation is one of several mechanisms controlling hepatic metabolism of fatty acids. Two transcription factors, namely SREBP1-c and PPARalpha, appear to be the main players controlling synthesis and degradation of fatty acids respectively. This chapter briefly presents fatty acid metabolism. The first part focuses on SREBP1-c contribution to the control of gene expression relevant to fatty acid synthesis and the main mechanisms of activation for this transcriptional program. The second part reviews the evidence for the involvement of PPARalpha in the control of fatty acid degradation and the key features of this nuclear receptor. Finally, the third part aims at summarizing recent advances in our current understanding of how these two transcription factors fit in the regulatory networks that sense hormones or nutrients, including cellular fatty acids, and govern the transcription of genes implicated in hepatic fatty acid metabolism.

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“…Although this tendency did not result in a significant difference in the area under the curve, the moderate but constantly elevated respiratory quotient of Arfrp1 livϪ/Ϫ mice indicated elevated carbohydrate oxidation. The assumption of a higher rate of carbohydrate metabolism was confirmed by measuring glucose oxidation via detection of 13 CO 2 accumulation in the breath of mice receiving 13 C-labeled glucose. Arfrp1 livϪ/Ϫ mice showed a tendency to oxidize more glucose than controls (t test, df ϭ 38.054, t ϭ Ϫ1.953, and P ϭ 0.058) (Fig.…”

Section: Impaired Glycogen Storage In the Liver And Reduced Blood Glumentioning

confidence: 94%

“…To measure in vivo glucose oxidation, 13 CO 2 breath tests of mice were performed as described previously (9).…”

Section: Generation Of Arfrp1mentioning

confidence: 99%

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GTPase ARFRP1 Is Essential for Normal Hepatic Glycogen Storage and Insulin-Like Growth Factor 1 Secretion

Hesse

Jaschke

Kanzleiter

et al. 2012

Molecular and Cellular Biology

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The GTPase ADP-ribosylation factor-related protein 1 (ARFRP1) is located at the trans-Golgi compartment and regulates the recruitment of Arf-like 1 (ARL1) and its effector golgin-245 to this compartment. Here, we show that liver-specific knockout of Arfrp1 in the mouse (Arfrp1 liv؊/؊ ) resulted in early growth retardation, which was associated with reduced hepatic insulin-like growth factor 1 (IGF1) secretion. Accordingly, suppression of Arfrp1 in primary hepatocytes resulted in a significant reduction of IGF1 release. However, the hepatic secretion of IGF-binding protein 2 (IGFBP2) was not affected in the absence of ARFRP1. In addition, Arfrp1 liv؊/؊ mice exhibited decreased glucose transport into the liver, leading to a 50% reduction of glycogen stores as well as a marked retardation of glycogen storage after fasting and refeeding. These abnormalities in glucose metabolism were attributable to reduced protein levels and intracellular retention of the glucose transporter GLUT2 in Arfrp1 liv؊/؊ livers. As a consequence of impaired glucose uptake into the liver, the expression levels of carbohydrate response element binding protein (ChREBP), a transcription factor regulated by glucose concentration, and its target genes (glucokinase and pyruvate kinase) were markedly reduced. Our data indicate that ARFRP1 in the liver is involved in the regulation of IGF1 secretion and GLUT2 sorting and is thereby essential for normal growth and glycogen storage.

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The role of protein translocation in the regulation of glycogen metabolism

Cited by 17 publications

References 71 publications

Regulation of hepatic glucose metabolism in health and disease

Regulation of hepatic glucose metabolism in health and disease

Transcriptional Regulation of Hepatic Fatty Acid Metabolism

GTPase ARFRP1 Is Essential for Normal Hepatic Glycogen Storage and Insulin-Like Growth Factor 1 Secretion

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