Studies in Glycogen Storage Diseases. I. Intestinal Glucose-6-Phosphatase Activity in Patients with Von Gierke's Disease and Their Parents*

Field, James B.; Epstein, Sheldon M.; Egan, Thomas J.

doi:10.1172/jci105230

Cited by 51 publications

(9 citation statements)

References 14 publications

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“…The hallmark of GSD1a, that is excessive deposition of glycogen in cells, has long been known to aVect not only the liver, but also the proximal tubules of the kidney (Lei et al 1996) and the small intestine (Field et al 1965). More recently, decreased glucose absorption after an oral glucose load was reported in GSD type 1 patients, in line with the important role of Glc6Pase in intestinal glucose absorption (Bodamer et al 2002;Santer et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Immunocytochemical localization of glucose 6-phosphatase and cytosolic phosphoenolpyruvate carboxykinase in gluconeogenic tissues reveals unsuspected metabolic zonation

Rajas

Jourdan-Pineau

Stefanutti

et al. 2007

Histochem Cell Biol

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Immunohistochemical analysis was used to define the precise cell-specific localization of Glucose-6-phosphatase (Glc6Pase) and cytosolic form of the phosphoenolpyruvate carboxykinase (PEPCK-C) in the digestive system (liver, small intestine and pancreas) and the kidney. Co-expression of Glc6Pase and PEPCK-C was shown to take place in hepatocytes, in proximal tubules of the cortex kidney and at the top of the villi of the small intestine suggesting that these tissues are all able to perform complete gluconeogenesis. On the other hand, intrahepatic bile ducts, collecting tubes of the nephron and the urinary epithelium in the calices of the kidney, as well as the crypts of the small intestine, express Glc6Pase without significant levels of PEPCK-C. In such cases, the function of Glc6Pase could be related to the transepithelial transport of glucose characteristic of these tissues, rather than to the neoformation of glucose. Lastly, PEPCK-C expression in the absence of Glc6Pase was noted in both the exocrine pancreas and the endocrine islets of Langerhans. Possible roles of PEPCK-C in exocrine pancreas might be the provision of gluconeogenic intermediates for further conversion into glucose in the liver, whereas PEPCK-C would be instrumental in pyruvate cycling, which has been suggested to play a regulatory role in insulin secretion by the beta-cells of the islets.

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Section: Discussionmentioning

confidence: 99%

Immunocytochemical localization of glucose 6-phosphatase and cytosolic phosphoenolpyruvate carboxykinase in gluconeogenic tissues reveals unsuspected metabolic zonation

Rajas

Jourdan-Pineau

Stefanutti

et al. 2007

Histochem Cell Biol

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“…Among the ESGSD I cohort, diarrhoea was reported in 35% of the GSD Ia patients. No common cause for diarrhoea in GSD Ia has been found [25,30,59,82]. The relation with disturbed enterocyte function due to lack of G6Pase activity remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I (ESGSD I)

Rake¹,

Visser²,

Labrune

et al. 2002

European Journal of Pediatrics

196

117

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there is still wide variation in methods of dietary and pharmacological treatment of glycogen storage disease type I. Intensive dietary treatment will improve, but not correct completely, clinical and biochemical status and fewer patients will die as a direct consequence of acute metabolic derangement. With ageing, more and more complications will develop of which progressive renal disease and the complications related to liver adenomas are likely to be two major causes of morbidity and mortality.

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“…However, some studies reported that GSD1a patients might also suffer from intermittent diarrhea due to entero-proctitis (Fine et al 1969;Milla et al 1978;Rake et al 2002b). An abnormal accumulation of glycogen has also been reported in the intestine of GSD1a patients (Field et al 1965).…”

Section: Kidney G6pc Knockout Micementioning

confidence: 99%

Lessons from new mouse models of glycogen storage disease type 1a in relation to the time course and organ specificity of the disease

Rajas

Clar

Gautier‐Stein

et al. 2014

J of Inher Metab Disea

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Patients with glycogen storage diseases type 1 (GSD1) suffer from life-threatening hypoglycaemia, when left untreated. Despite an intensive dietary treatment, patients develop severe complications, such as liver tumors and renal failure, with aging. Until now, the animal models available for studying the GSD1 did not survive after weaning. To gain further insights into the molecular mechanisms of the disease and to evaluate potential treatment strategies, we have recently developed novel mouse models in which the catalytic subunit of glucose-6 phosphatase (G6pc) is deleted in each glucose-producing organ specifically. For that, B6.G6pc(ex3lox/ex3lox) mice were crossed with transgenic mice expressing a recombinase under the control of the serum albumin, the kidney androgen protein or the villin promoter, in order to obtain liver, kidney or intestine G6pc(-/-) mice, respectively. As opposed to total G6pc knockout mice, tissue-specific G6pc deficiency allows mice to maintain their blood glucose by inducing glucose production in the other gluconeogenic organs. Even though it is considered that glucose is produced mainly by the liver, liver G6pc(-/-) mice are perfectly viable and exhibit the same hepatic pathological features as GSD1 patients, including the late development of hepatocellular adenomas and carcinomas. Interestingly, renal G6pc(-/-) mice developed renal symptoms similar to the early human GSD1 nephropathy. This includes glycogen overload that leads to nephromegaly and morphological and functional alterations in the kidneys. Thus, our data suggest that renal G6Pase deficiency per se is sufficient to induce the renal pathology of GSD1. Therefore, these new mouse models should allow us to improve the strategies of treatment on both nutritional and pharmacological points of view.

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Studies in Glycogen Storage Diseases. I. Intestinal Glucose-6-Phosphatase Activity in Patients with Von Gierke's Disease and Their Parents*

Cited by 51 publications

References 14 publications

Immunocytochemical localization of glucose 6-phosphatase and cytosolic phosphoenolpyruvate carboxykinase in gluconeogenic tissues reveals unsuspected metabolic zonation

Immunocytochemical localization of glucose 6-phosphatase and cytosolic phosphoenolpyruvate carboxykinase in gluconeogenic tissues reveals unsuspected metabolic zonation

Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I (ESGSD I)

Lessons from new mouse models of glycogen storage disease type 1a in relation to the time course and organ specificity of the disease

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