Identification and characterization of a cDNA and the gene encoding the mouse ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein

Boustead, JN; Martin, Carley; Oeser, JK; Svitek, CA; Hunter, SI; Hutton, JC; O'Brien, RM

doi:10.1677/jme.0.0320033

Cited by 21 publications

(23 citation statements)

References 57 publications

(87 reference statements)

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“…In line with our results, other studies have also demonstrated very low or even undetectable levels of G6PC1 mRNA in the small intestine of adult rats (24,36). Moreover, both our results and those of others (10) showed that the principal G6PC isoform expressed in the small intestine in adult rats was the ubiquitous (G6PC3) isoform. Interestingly, we observed that the expression of intestinal G6PC1 and G6PC3 was stimulated by feeding, regardless of the diet.…”

Section: Discussionsupporting

confidence: 92%

Liver glyconeogenesis: a pathway to cope with postprandial amino acid excess in high-protein fed rats?

Azzout‐Marniche¹,

Gaudichon²,

Blouet³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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This paper provides molecular evidence for a liver glyconeogenic pathway, that is, a concomitant activation of hepatic gluconeogenesis and glycogenesis, which could participate in the mechanisms that cope with amino acid excess in high-protein (HP) fed rats. This evidence is based on the concomitant upregulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression, downregulation of glucose 6-phosphatase catalytic subunit (G6PC1) gene expression, an absence of glucose release from isolated hepatocytes and restored hepatic glycogen stores in the fed state in HP fed rats. These effects are mainly due to the ability of high physiological concentrations of portal blood amino acids to counteract glucagon-induced liver G6PC1 but not PEPCK gene expression. These results agree with the idea that the metabolic pathway involved in glycogen synthesis is dependent upon the pattern of nutrient availability. This nonoxidative glyconeogenic disposal pathway of gluconeogenic substrates copes with amino excess and participates in adjusting both amino acid and glucose homeostasis. In addition, the pattern of PEPCK and G6PC1 gene expression provides evidence that neither the kidney nor the small intestine participated in gluconeogenic glucose production under our experimental conditions. Moreover, the main glucose-6-phosphatase (G6Pase) isoform expressed in the small intestine is the ubiquitous isoform of G6Pase (G6PC3) rather than the G6PC1 isoform expressed in gluconeogenic organs.high-protein diet; glyconeogenesis; glucose 6-phosphatase; phosphoenolpyruvate carboxykinase; liver THE CONSEQUENCES OF HIGH-PROTEIN feeding on the regulation and pathways of glucose disposal through glycogen metabolism and gluconeogenesis remain unclear. High-protein feeding induced both insulin and glucagon secretion in the fed state, associated with the repletion of glycogen stores (3, 45, 52), whereas excess dietary amino acids are metabolized within tissues and the derived nitrogen released into the circulation in the form of glutamine, alanine, serine, and glycine (28, 56). These amino acids are subsequently taken up by the liver, and the nitrogen is converted to urea and glutamine (12,28), the bulk of their carbon skeleton being converted to glucose through hepatic gluconeogenesis (8,29,37,51). This concomitant activation of both glycogen synthesis and gluconeogenesis in the fed state raises the question as to whether the glucose-6-P produced from gluconeogenic amino acid precursors could be directly channeled to glycogen through glycogenesis instead of being excreted as glucose from hepatocytes. This pathway of glyconeogenesis has been discussed over several decades, but despite some evidence during refeeding (49), its significance and molecular basis remain poorly understood (4, 30), and it has not previously been hypothesized under high-protein feeding.It is established that insulin stimulates glycogen synthesis and represses the gluconeogenic production of glucose, whereas glucagon represses glycogen synthesis and stimulates glucose ...

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Section: Discussionsupporting

confidence: 92%

Liver glyconeogenesis: a pathway to cope with postprandial amino acid excess in high-protein fed rats?

Azzout‐Marniche¹,

Gaudichon²,

Blouet³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Two G6Pase-related proteins have recently been identified designated the islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) (Arden, et al 1999; Martin, et al 2001; Wang, et al 2007b) and the ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein (UGRP), also known as G6Pase-beta. The encoded proteins exhibit around 50% sequence identity, exhibit a common 9 transmembrane domain topology and are all localized to the endoplasmic reticulum (Boustead, et al 2004; Martin, et al 2002). …”

Section: Introductionmentioning

confidence: 99%

Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression

Martin¹,

Flemming²,

Wang³

et al. 2008

Journal of Molecular Endocrinology

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Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes. IGRP is selectively expressed in islet b cells and polymorphisms in the IGRP gene have recently been associated with variations in fasting blood glucose levels and cardiovascular-associated mortality in humans. Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2. We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2. Single binding sites for these factors were identified in the proximal IGRP promoter, mutation of which resulted in decreased IGRP fusion gene expression in bTC-3, Hamster insulinoma tumor (HIT), and Min6 cells. ChiP assays have shown that the islet-enriched transcription factor Pdx-1 also binds the IGRP promoter, but mutational analysis of four Pdx-1 binding sites in the proximal IGRP promoter revealed surprisingly little effect of Pdx-1 binding on IGRP fusion gene expression in bTC-3 cells. In contrast, in both HIT and Min6 cells mutation of these four Pdx-1 binding sites resulted in a w50% reduction in fusion gene expression. These data suggest that the same group of islet-enriched transcription factors, namely Pdx-1, Pax-6, MafA, BETA2, and Foxa2, directly or indirectly regulate expression of the two major autoantigens in type 1 diabetes.

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“…T he glucose-6-phosphatase catalytic subunit (G6PC) gene family is comprised of three members: G6PC, which is predominantly expressed in liver and kidney and plays a major role in glucose homeostasis (1); G6PC2, an islet-specific G6PC-related protein (IGRP) of uncertain function (2-4); and G6PC3, a ubiquitously expressed G6PC-related protein that confers low glucose-6-phosphate (G6P) activity to a broad range of tissues (5)(6)(7)(8). The encoded proteins exhibit ϳ50% sequence identity, exhibit a common nine-transmembrane domain topology, and are all localized to the endoplasmic reticulum (5,6).…”

mentioning

confidence: 99%

“…The encoded proteins exhibit ϳ50% sequence identity, exhibit a common nine-transmembrane domain topology, and are all localized to the endoplasmic reticulum (5,6).…”

mentioning

confidence: 99%

Long-Range Enhancers Are Required to Maintain Expression of the Autoantigen Islet-Specific Glucose-6-Phosphatase Catalytic Subunit–Related Protein in Adult Mouse Islets In Vivo

et al. 2008

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OBJECTIVE-Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is selectively expressed in islet ␤-cells and is a major autoantigen in both mouse and human type 1 diabetes. This study describes the use of a combination of transgenic and transfection approaches to characterize the gene regions that confer the islet-specific expression of IGRP.RESEARCH DESIGN AND METHODS-Transgenic mice were generated containing the IGRP promoter sequence from Ϫ306, Ϫ911, or Ϫ3911 to ϩ3 ligated to a LacZ reporter gene. Transgene expression was monitored by 5-bromo-4-chloro-3-indolyl-␤-D-galactopyranoside staining of pancreatic tissue.RESULTS-In all the transgenic mice, robust LacZ expression was detected in newborn mouse islets, but expression became mosaic as animals aged, suggesting that additional elements are required for the maintenance of IGRP gene expression. VISTA analyses identified two conserved regions in the distal IGRP promoter and one in the third intron. Transfection experiments demonstrated that all three regions confer enhanced luciferase reporter gene expression in ␤TC-3 cells when ligated to a minimal IGRP promoter. A transgene containing all three conserved regions was generated by using a bacterial recombination strategy to insert a LacZ cassette into exon 5 of the IGRP gene. Transgenic mice containing a 15-kbp fragment of the IGRP gene were then generated. This transgene conferred LacZ expression in newborn mouse islets; however, expression was still suppressed as animals aged. CONCLUSIONS-The

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Identification and characterization of a cDNA and the gene encoding the mouse ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein

Cited by 21 publications

References 57 publications

Liver glyconeogenesis: a pathway to cope with postprandial amino acid excess in high-protein fed rats?

Liver glyconeogenesis: a pathway to cope with postprandial amino acid excess in high-protein fed rats?

Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression

Long-Range Enhancers Are Required to Maintain Expression of the Autoantigen Islet-Specific Glucose-6-Phosphatase Catalytic Subunit–Related Protein in Adult Mouse Islets In Vivo

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