Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2009) 19 S29

SFEBES2009 Symposia The endoplasmic reticulum – an important link between inflammation, stress and metabolism (4 abstracts)

Glucose sensing in the endoplasmic reticulum: maintaining the cellular environment

G G Lavery


University of Birmingham, Birmingham, UK.

It is becoming increasingly evident that pathways exist within the (ER) that can impact upon cellular redox status, glucocorticoid metabolism and glucose homeostasis.

Within the ER of the liver, glucose-6-phosphatase (G6Pase) and glucose 6-phosphate (G6P) transporter (G6PT) work together to increase blood glucose concentrations by performing the terminal step in both glycogenolysis and gluconeogenesis. The G6Pase ‘shares’ G6P with hexose-6-phosphate-dehydrogenase (H6PDH), an enzyme that produces NADPH allowing 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to reactivate glucocorticoids. Deficiency of the G6Pase or G6PT gives rise to glycogen storage diseases (GSD) -1a and -1b respectively. Though rare, patients with GSD1a and 1b provide evidence that G6P metabolism via H6PDH modulates 11β-HSD1 activity. Similarly, a lack of H6PDH gives rise to patients with ‘cortisone reductase deficiency’ in which insufficient ER NADPH generation prevents 11β-HSD1 reductase activity. In common, these conditions have highlighted a novel link between hepatic glucose metabolism, redox status and correct functioning of the hypothalamo–pituitary–adrenal axis.

More recently, studies in H6PDH null mice have begun to identify the importance of ER metabolism to skeletal muscle. Mice display a vacuolating myopathy associated with changes in glucose homeostasis and activation of the ER stress response. As muscle is not a traditional gluconeogenic tissue, these data highlight the importance of H6PDH and ER glucose metabolism to maintaining normal metabolic function.

It is becoming clear that glucose sensing within the ER is important but is not confined to traditional tissues. ER pathways involving G6PT, H6PDH and 11β-HSD1 in peripheral tissues such as muscle are key to maintaining intracellular homeostasis. Human and rodent systems have been vital to elucidating novel aspects of ER glucose sensing and utilisation and will continue to aid further understanding of its role in normal physiology.

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