ArticleDiabetologia2011
Tissue-specific dysregulation of hexose-6-phosphate dehydrogenase and glucose-6-phosphate transporter production in db/db mice as a model of type 2 diabetes.
Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Mifepristone Improves Adipose Tissue Insulin Sensitivity in Insulin Resistant Individuals.The Journal of clinical endocrinology and metabolism · 2021Trial
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- Multiomics analyses reveal that PRMT5 regulates membrane transport and cholesterol synthesis in white adipocytes.iMetaOmics · 2025Article
- Alterations in glucocorticoid homeostasis following sleeve gastrectomy.bioRxiv : the preprint server for biology · 2025Article
- Simulation of the crosstalk between glucose and acetaminophen metabolism in a liver zonation model.Frontiers in pharmacology · 2022Article
- Association of increased renalJournal of clinical biochemistry and nutrition · 2020Article
- Lack of adipose-specific hexose-6-phosphate dehydrogenase causes inactivation of adipose glucocorticoids and improves metabolic phenotype in mice.Clinical science (London, England : 1979) · 2019Article
- Enhanced hexose-6-phosphate dehydrogenase expression in adipose tissue may contribute to diet-induced visceral adiposity.International journal of obesity (2005) · 2018Article
- Interplay between H6PDH and 11β-HSD1 implicated in the pathogenesis of type 2 diabetes mellitus.Bioorganic & medicinal chemistry letters · 2017Article
- Increased glycogen synthase kinase-3β and hexose-6-phosphate dehydrogenase expression in adipose tissue may contribute to glucocorticoid-induced mouse visceral adiposity.International journal of obesity (2005) · 2016Article
- Amphetamine withdrawal differentially affects hippocampal and peripheral corticosterone levels in response to stress.Brain research · 2016Article
- 11β-Hydroxysteroid dehydrogenase type 1 shRNA ameliorates glucocorticoid-induced insulin resistance and lipolysis in mouse abdominal adipose tissue.American journal of physiology. Endocrinology and metabolism · 2015Article
- Transgenic overexpression of hexose-6-phosphate dehydrogenase in adipose tissue causes local glucocorticoid amplification and lipolysis in male mice.American journal of physiology. Endocrinology and metabolism · 2014Article
- Effects of selective and non-selective glucocorticoid receptor II antagonists on rapid-onset diabetes in young rats.PloS one · 2014Article
- Central proliferation and neurogenesis is impaired in type 2 diabetes and prediabetes animal models.PloS one · 2014Article
- Liver glucose-6-phosphatase proteins in suckling and weaned grey seal pups: structural similarities to other mammals and relationship to nutrition, insulin signalling and metabolite levels.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2013Article
- Specific reduction of G6PT may contribute to downregulation of hepatic 11β-HSD1 in diabetic mice.Journal of molecular endocrinology · 2013Article
- Mifepristone promotes adiponectin production and improves insulin sensitivity in a mouse model of diet-induced-obesity.PloS one · 2013Article
- Involvement of GR and p300 in the induction of H6PD by cortisol in human amnion fibroblasts.Endocrinology · 2012Article
- A rodent model of rapid-onset diabetes induced by glucocorticoids and high-fat feeding.Disease models & mechanisms · 2012Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
aims/hypothesisTissue-specific amplification of glucocorticoid action through 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) affects the development of the metabolic syndrome. Hexose-6-phosphate dehydrogenase (H6PDH) mediates intracellular NADPH availability for 11β-HSD1 and depends on the glucose-6-phosphate transporter (G6PT). Little is known about the tissue-specific alterations of H6PDH and G6PT and their contributions to local glucocorticoid action in db/db mice.
methodsWe characterised the role of H6PDH and G6PT in pre-receptor metabolism of glucocorticoids by examining the production of the hepatic 11β-HSD1-H6PDH-G6PT system in db/db mice.
resultsWe observed that increased production of hepatic H6PDH in db/db mice was paralleled by upregulation of hepatic G6PT production and responded to elevated circulating levels of corticosterone. Treatment of db/db mice with the glucocorticoid antagonist RU486 markedly reduced production of both H6PDH and 11β-HSD1 and improved hyperglycaemia and insulin resistance. The reduction of H6PDH and 11β-HSD1 production by RU486 was accompanied by RU486-induced suppression of hepatic G6pt (also known as Slc37a4) mRNA. Incubation of mouse primary hepatocytes with corticosterone enhanced G6PT and H6PDH production with corresponding activation of 11β-HSD1 and PEPCK: effects that were blocked by RU486. Knockdown of H6pd by small interfering RNA showed effects comparable with those of RU486 for attenuating the corticosterone-induced H6PDH production and 11ß-HSD1 reductase activity in these intact cells. Addition of the G6PT inhibitor chlorogenic acid to primary hepatocytes suppressed H6PDH production. CONCLUSIONS/
interpretationThese findings suggest that increased hepatic H6PDH and G6PT production contribute to 11β-HSD1 upregulation of local glucocorticoid action that may be related to the development of type 2 diabetes.
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