Histone deacetylase 3 inhibition improves glycaemia and insulin secretion in obese diabetic rats
| Autor: | Steen Seier Poulsen, Thomas Mandrup-Poulsen, Thomas Galbo, Morten Lundh |
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| Rok vydání: | 2015 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Type 2 diabetes Fatty Acids Nonesterified Weight Gain Histone Deacetylases Diabetes Mellitus Experimental Endocrinology Insulin resistance Insulin-Secreting Cells Internal medicine Diabetes mellitus Insulin Secretion Internal Medicine medicine Animals Insulin Obesity business.industry medicine.disease HDAC3 In vitro Rats Rats Zucker Histone Deacetylase Inhibitors Diabetes Mellitus Type 2 Hyperglycemia Glucose Clamp Technique Histone deacetylase Insulin Resistance Beta cell business |
| Zdroj: | Diabetes, Obesity and Metabolism. 17:703-707 |
| ISSN: | 1462-8902 |
| Popis: | Failure of pancreatic β cells to compensate for insulin resistance is a prerequisite for the development of type 2 diabetes. Sustained elevated circulating levels of free fatty acids and glucose contribute to β-cell failure. Selective inhibition of histone deacetylase (HDAC)-3 protects pancreatic β cells against inflammatory and metabolic insults in vitro. In the present study, we tested the ability of a selective HDAC3 inhibitor, BRD3308, to reduce hyperglycaemia and increase insulin secretion in a rat model of type 2 diabetes. At diabetes onset, an ambulatory hyperglycaemic clamp was performed. HDAC3 inhibition improved hyperglycaemia over the study period without affecting weight gain. At the end of the hyperglycaemic clamp, circulating insulin levels were significantly higher in BRD3308-treated rats. Pancreatic insulin staining and contents were also significantly higher. These findings highlight HDAC3 as a key therapeutic target for β-cell protection in type 2 diabetes. |
| Databáze: | OpenAIRE |
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