Is ?Cushing?s disease of the omentum? an affliction of mouse and men?

Walker, Brian R.

doi:10.1007/s00125-004-1390-y

Cited by 15 publications

(15 citation statements)

References 34 publications

(34 reference statements)

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“…However, extra-adrenal conversion of cortisone to cortisol via 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD-1) can result in high local concentrations of cortisol. This observation focused attention on the possibility that tissue-specific synthesis of glucocorticoids may contribute to the pathogenesis of insulin resistance and other components of the so called "metabolic syndrome" (1). The enzyme 11␤-HSD-2 (which converts cortisol to cortisone) is present primarily in the kidney, whereas 11␤-HSD-1 (which converts cortisone to cortisol) is present in both liver and adipose tissue with in vitro activity being greater in omental than subcutaneous fat deposits (2)(3)(4)(5).…”

mentioning

confidence: 99%

Liver Is the Site of Splanchnic Cortisol Production in Obese Nondiabetic Humans

Basu

Grudzień

et al. 2009

Diabetes

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OBJECTIVE-To determine the contribution of liver and viscera to splanchnic cortisol production in humans. RESEARCH DESIGN AND METHODS-D4cortisol was infused intravenously; arterial, portal venous, and hepatic venous blood was sampled; and liver and visceral fat were biopsied in subjects undergoing bariatric surgery.RESULTS-Ratios of arterial and portal vein D4 cortisol/cortisol total (0.06 Ϯ 0.01 vs. 0.06 Ϯ 0.01) and D4 cortisol/D3 cortisol (1.80 Ϯ 0.14 vs. 1.84 Ϯ 0.14) did not differ, indicating that no visceral cortisol production or conversion of D4 cortisol to D3 cortisol via 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD-1) occurred. Conversely, ratios of both D4 cortisol to cortisol total (0.05 Ϯ 0.01; P Ͻ 0.05) and D4 cortisol to D3 cortisol (1.33 Ϯ 0.11; P Ͻ 0.001) were lower in the hepatic vein than in the portal vein, indicating production of both cortisol and D3 cortisol by the liver. The viscera did not produce either cortisol (Ϫ8.1 Ϯ 2.6 g/min) or D3 cortisol (Ϫ0.2 Ϯ 0.1 g/min). In contrast, the liver produced both cortisol (22.7 Ϯ 3.90 g/min) and D3 cortisol (1.9 Ϯ 0.4 g/min) and accounted for all splanchnic cortisol and D3 cortisol production. Additionally, 11␤-HSD-1 mRNA was approximately ninefold higher (P Ͻ 0.01) in liver than in visceral fat. Although 11␤-HSD-2 gene expression was very low in visceral fat, the viscera released cortisone (P Ͻ 0.001) and D3 cortisone (P Ͻ 0.01) into the portal vein. CONCLUSIONS-The liver accounts for all splanchnic cortisol production in obese nondiabetic humans. In contrast, the viscera releases cortisone into the portal vein, thereby providing substrate for intrahepatic cortisol production. Diabetes 58:39-45, 2009 A lthough it has been long known that glucocorticoids are potent regulators of glucose, fat, and protein metabolism, glucocorticoids have not been thought to cause insulin resistance in either obese or diabetic individuals because plasma concentrations do not differ from those present in lean nondiabetic subjects. However, extra-adrenal conversion of cortisone to cortisol via 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD-1) can result in high local concentrations of cortisol. This observation focused attention on the possibility that tissue-specific synthesis of glucocorticoids may contribute to the pathogenesis of insulin resistance and other components of the so called "metabolic syndrome" (1). The enzyme 11␤-HSD-2 (which converts cortisol to cortisone) is present primarily in the kidney, whereas 11␤-HSD-1 (which converts cortisone to cortisol) is present in both liver and adipose tissue with in vitro activity being greater in omental than subcutaneous fat deposits (2-5). Inhibition (6) or knockout (7-9) of 11␤-HSD-1 in mice improves hepatic insulin action and protects against obesity and hyperglycemia. Conversely, selective overexpression of 11␤-HSD-1 in adipose tissue in mice results in development of visceral obesity, hyperglycemia, hyperlipidemia, and hypertension (7-11).Using a novel tracer infusion method, Andrew et al. (12) demonstrated...

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confidence: 99%

Liver Is the Site of Splanchnic Cortisol Production in Obese Nondiabetic Humans

Basu

Grudzień

et al. 2009

Diabetes

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“…The observation that 11␤-HSD-1 message and activity is present in fat, muscle, and liver has engendered considerable interest regarding the possible contribution of local generation of cortisol to the pathogenesis of insulin resistance (1,2). This interest has been further heightened by studies showing that overexpression of 11␤-HSD-1 in mice leads to obesity, hypertension, and hyperglycemia (10 -11), whereas inhibition or knockout of this enzyme protects against these abnormalities (7-9).…”

Section: Discussionmentioning

confidence: 99%

“…However, the recognition that extra-adrenal conversion of cortisone to cortisol can occur via the bidirectional enzyme 11␤ hydroxysteroid dehydrogenase type 1 (11␤-HSD-1) has focused attention on the possibility that tissue-specific synthesis of glucocorticoids contributes to the pathogenesis of insulin resistance and other components of the so-called "metabolic syndrome" (1,2).…”

mentioning

confidence: 99%

Obesity and Type 2 Diabetes Do Not Alter Splanchnic Cortisol Production in Humans

Basu¹,

Singh²,

Basu³

et al. 2005

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Tissue-specific conversion of cortisone to cortisol via the 11β-hydroxysteroid dehydrogenase type 1 enzyme pathway (11β-HSD-1) results in high local cortisol concentrations [1]. 11β-HSD-1 is present in multiple tissues, including the liver and adipose tissue, with activity being greater in omental than in subcutaneous fat [2–5].…”

Section: Introductionmentioning

confidence: 99%

Hepatic 11β-hydroxysteroid dehydrogenase type 1 activity in obesity and type 2 diabetes using a novel triple tracer cortisol technique

et al. 2014

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Aims/hypothesis Dysregulation of 11β-hydroxysteroid dehydrogenase (11β-HSD) enzyme activities are implicated in the pathogenesis of obesity and insulin resistance. The aim of the study was to determine whether hepatic 11β-HSD type 1 (11β-HSD-1) enzyme activity differs in people with and without obesity and type 2 diabetes. Methods We measured hepatic 11β-HSD-1 activity in the overnight fasted state in 20 lean non-diabetic participants (LND), 21 overweight/obese non-diabetic participants (OND) and 20 overweight/obese participants with type 2 diabetes (ODM) using a non-invasive approach. One mg doses of [9,12,12-2H3]cortisol (D cortisol) and [4-13C]cortisone ([13C]cortisone) were ingested, while [1,2,6,7-3H]cortisol ([3H] cortisol) was infused intravenously to enable concurrent measurements of first-pass hepatic extraction of ingested D cortisol and hepatic conversion of ingested [13C]cortisone to C13 cortisol derived from the ingested cortisone (a measure of 11β-HSD-1 activity in the liver) using an isotope dilution technique. One-way ANOVA models and Kruskal–Wallis tests were used to test the hypothesis. Results Plasma D cortisol and C13 cortisol concentrations were lower in OND than in LND (p<0.05) over 6 h of the study. There was no difference (p=0.15) in C13 and D cortisol concentrations between OND and ODM and between LND and ODM for the same study period. Hepatic conversion of [13C]cortisone to C13 cortisol was similar between groups. Conclusions/interpretation Hepatic conversion of [13C]cortisone to C13 cortisol did not differ between the groups studied. We conclude that hepatic 11β-HSD-1 activity is similar in individuals who are overweight/obese or who have type 2 diabetes.

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Is ?Cushing?s disease of the omentum? an affliction of mouse and men?

Cited by 15 publications

References 34 publications

Liver Is the Site of Splanchnic Cortisol Production in Obese Nondiabetic Humans

Liver Is the Site of Splanchnic Cortisol Production in Obese Nondiabetic Humans

Obesity and Type 2 Diabetes Do Not Alter Splanchnic Cortisol Production in Humans

Hepatic 11β-hydroxysteroid dehydrogenase type 1 activity in obesity and type 2 diabetes using a novel triple tracer cortisol technique

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