Objective: The cortisol-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies glucocorticoid levels in liver and adipose tissue. 11β-HSD1 inhibitors are being developed to treat type 2 diabetes. In obesity, 11β-HSD1 is increased in adipose tissue but decreased in liver. The benefits of pharmacological inhibition may be reduced if hepatic 11β-HSD1 is similarly decreased in obese patients with type 2 diabetes. To examine this, we quantified in vivo whole-body, splanchnic, and hepatic 11β-HSD1 activity in obese type 2 diabetic subjects.
Research Design And Methods: Ten obese men with type 2 diabetes and seven normal-weight control subjects were infused with 9,11,12,12-[(2)H](4)cortisol (40%) and cortisol (60%) at 1.74 mg/h. Adrenal cortisol secretion was suppressed with dexamethasone. Samples were obtained from the hepatic vein and an arterialized hand vein at steady state and after oral administration of cortisone (5 mg) to estimate whole-body and liver 11β-HSD1 activity using tracer dilution.
Results: In obese type 2 diabetic subjects, the appearance rate of 9,12,12-[(2)H](3)cortisol in arterialized blood was increased (35 ± 2 vs. 29 ± 1 nmol/min, P < 0.05), splanchnic 9,12,12-[(2)H](3)cortisol production was not reduced (29 ± 6 vs. 29 ± 6 nmol/min), and cortisol appearance in the hepatic vein after oral cortisone was unchanged.
Conclusions: Whole-body 11β-HSD1 activity is increased in obese men with type 2 diabetes, whereas liver 11β-HSD1 activity is sustained, unlike in euglycemic obesity. This supports the concept that inhibitors of 11β-HSD1 are likely to be most effective in obese type 2 diabetic subjects.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046832 | PMC |
| http://dx.doi.org/10.2337/db10-0726 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
N1 derived lipoteichoic acid alleviates insulin resistance in association with modulation of the gut microbiota and amino acid metabolism.
Food Funct
January 2025
College of Food Science and Technology, Zhejiang University of Technology, Hangzhou 310014, China.
This study aimed to investigate the effects of heat-killed N1 (HK-N1) and lipoteichoic acid (LTA) derived from it on alleviating insulin resistance by modulating the gut microbiota and amino acid metabolism. High-fat diet (HFD)-fed mice were administered live bacteria or HK-N1, and the results demonstrated that HK-N1 significantly reduced epididymal adipocyte size and serum low density lipoprotein-cholesterol, and improved insulin resistance by increasing the YY peptide and glucagon-like peptide levels. HK-N1 also modulated the gut microbiome composition, enhancing microbiota uniformity and reducing the abundance of , and .
View Article and Find Full Text PDFBudget impact analysis of insulin glargine vs. isophane protamine insulin treatment for patients with type-2 diabetes and severe hypoglycemia in Thailand.
Front Public Health
January 2025
Rajavithi Hospital, College of Medicine, Ministry of Public Health, Rangsit University, Bangkok, Thailand.
Objective: This study aimed to assess the financial impact of different adoption rates of insulin glargine (IGlar) treatment compared to isophane protamine (neutral protamine hagedorn [NPH]) insulin treatment for patients with type-2 diabetes (T2D) and severe hypoglycemia in Thailand from the payer's perspective.
Methods: The budget impact analysis (BIA) model over a period of 5 years was used to estimate the net budget impact (NBI) of IGlar treatment by comparing the total budget expenditures under two scenarios: scenario 1 involved only NPH insulin and scenario 2 included the introduction of IGlar. The total budget included either the cost of insulin or a combination of the costs of insulin and the expense related to severe hypoglycemia.
The association between working hours and working type with non-alcoholic fatty liver disease: results from the NHANES 1999-2014.
Front Endocrinol (Lausanne)
January 2025
Department of Pediatric Laboratory, Affiliated Children's Hospital of Jiangnan University, Wuxi Children's Hospital, Wuxi, Jiangsu, China.
Background: Previous research has indicated that long working hours are connected to a variety of health conditions, including nonalcoholic fatty liver disease (NAFLD). However, this association which has been observed in more population is limited. Our research is designed to evaluate the association between working hours, working type, and NAFLD.
View Article and Find Full Text PDFPhysician-Visit Frequency and Its Impact on Glycemic Control in People With Type 2 Diabetes: Quantifying Care Acceptance Parameters From Retrospective Electronic Health Record Data.
Cureus
December 2024
Obstetrics and Gynecology, Shree Guru Gobind Singh Tricentenary University Medical College, Hospital and Research Institute, Gurugram, IND.
Objective: Type 2 diabetes is a metabolic disorder characterized by insulin resistance and hyperglycemia affecting many individuals worldwide. For effective management, adherence to recommended physician visits is important, along with lifestyle modification and pharmacological interventions. Regular doctor visits can improve adherence and help prevent complications.
View Article and Find Full Text PDFExploring the links between gallstone disease, non-alcoholic fatty liver disease, and kidney stones: A path to comprehensive prevention.
World J Gastroenterol
January 2025
Université de Bourgogne, Institut Agro-INRAe, Dijon 21000, France.
The recent study exploring the bidirectional associations between gallstone disease, non-alcoholic fatty liver disease, and kidney stone disease highlights a critical concern in chronic disease management. Given the rising global prevalence of these conditions, understanding their interconnections is essential. The study emphasizes the importance of shared risk factors, such as obesity, type 2 diabetes, dyslipidemia, and oxidative stress, and calls for multidisciplinary screening strategies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!