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11? Hydroxysteroid dehydrogenase - 1 activity in type 2 diabetes mellitus: a comparative study.

ABSTRACT: BACKGROUND:A comparative study of 11 ? HSD 1 activity in type 2 diabetes mellitus subjects with respect to fasting blood glucose and other metabolic parameters was conducted. METHODS:A case control experimental study was performed enrolling thirty type 2 diabetes mellitus patients and thirty age, gender and BMI matched controls using cortisone acetate test. RESULTS:The rise of serum cortisol after oral 25?mg cortisone acetate from baseline (dexamethasone suppressed level) is higher in subjects with type 2 diabetes and is associated with exercise, BMI, SGOT but not daily calorie intake, lipid parameters and thyroid status. Fasting blood glucose after overnight 1?mg oral dexamethasone is a strong predictor of 11HSD1 activity, irrespective of presence of type 2 diabetes. CONCLUSION:11? HSD 1 activity is higher in type 2 diabetes mellitus subjects, especially those who are lean. Future 11 ? HSD 1 inhibitors targeting metabolic syndrome, will be most useful in those with increased fasting blood glucose. The role of DHEAS and vitamin D status needs to be explored.

SUBMITTER: Shukla R

PROVIDER: S-EPMC6345010 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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11β Hydroxysteroid dehydrogenase - 1 activity in type 2 diabetes mellitus: a comparative study.

Shukla Ravindra R Basu Asish Kumar AK Mandal Biplab B Mukhopadhyay Pradip P Maity Animesh A Chakraborty Satyam S Devrabhai Praveen Kumar PK

BMC endocrine disorders 20190124 1

<h4>Background</h4>A comparative study of 11 β HSD 1 activity in type 2 diabetes mellitus subjects with respect to fasting blood glucose and other metabolic parameters was conducted.<h4>Methods</h4>A case control experimental study was performed enrolling thirty type 2 diabetes mellitus patients and thirty age, gender and BMI matched controls using cortisone acetate test.<h4>Results</h4>The rise of serum cortisol after oral 25 mg cortisone acetate from baseline (dexamethasone suppressed level) i ...[more]

PMID: 30678666

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Project description:BackgroundRecent studies have shown that production of cortisol not only takes place in several non-adrenal peripheral tissues such as epithelial cells but, also, the local inter-conversion between cortisone and cortisol is regulated by the 11?-hydroxysteroid dehydrogenases (11?-HSDs). However, little is known about the activity of this non-adrenal glucocorticoid system in cancers.MethodsThe presence of a functioning glucocorticoid system was assessed in human skin squamous cell carcinoma (SCC) and melanoma and further, in 16 epithelial cell lines from 8 different tissue types using ELISA, western blotting and immunofluorescence. 11?-HSD2 was inhibited both pharmacologically and by siRNA technology. Naïve CD8+ T cells were used to test the paracrine effects of cancer-derived cortisol on the immune system in vitro. Functional assays included cell-cell adhesion and cohesion in two- and three-dimensional models. Immunohistochemical data of 11?-HSD expression were generated using tissue microarrays of 40 cases of human SCCs as well as a database featuring 315 cancer cases from 15 different tissues.ResultsWe show that cortisol production is a common feature of malignant cells and has paracrine functions. Cortisol production correlated with the magnitude of glucocorticoid receptor (GR)-dependent inhibition of tumour-specific CD8+ T cells in vitro. 11?-HSDs were detectable in human skin SCCs and melanoma. Analyses of publicly available protein expression data of 11?-HSDs demonstrated that 11?-HSD1 and -HSD2 were dysregulated in the majority (73%) of malignancies. Pharmacological manipulation of 11?-HSD2 activity by 18?-glycyrrhetinic acid (GA) and silencing by specific siRNAs modulated the bioavailability of cortisol. Cortisol also acted in an autocrine manner and promoted cell invasion in vitro and cell-cell adhesion and cohesion in two- and three-dimensional models. Immunohistochemical analyses using tissue microarrays showed that expression of 11?-HSD2 was significantly reduced in human SCCs of the skin.ConclusionsThe results demonstrate evidence of a cancer-associated glucocorticoid system and show for the first time, the functional significance of cancer-derived cortisol in tumour progression.

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11? Hydroxysteroid dehydrogenase - 1 activity in type 2 diabetes mellitus: a comparative study.

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11β Hydroxysteroid dehydrogenase - 1 activity in type 2 diabetes mellitus: a comparative study.

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