Histone deacetylase 3 inhibition improves glycaemia and insulin secretion in obese diabetic rats
Publikation: Bidrag til tidsskrift › Letter › Forskning › fagfællebedømt
Standard
Histone deacetylase 3 inhibition improves glycaemia and insulin secretion in obese diabetic rats. / Lundh, Morten; Galbo, Thomas; Poulsen, Steen Seier; Mandrup-Poulsen, Thomas.
I: Diabetes, Obesity and Metabolism, Bind 17, Nr. 7, 07.2015, s. 703-7.Publikation: Bidrag til tidsskrift › Letter › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Histone deacetylase 3 inhibition improves glycaemia and insulin secretion in obese diabetic rats
AU - Lundh, Morten
AU - Galbo, Thomas
AU - Poulsen, Steen Seier
AU - Mandrup-Poulsen, Thomas
N1 - This article is protected by copyright. All rights reserved.
PY - 2015/7
Y1 - 2015/7
N2 - 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. Here we tested the ability of a selective HDAC3 inhibitor, BRD3308, to reduce hyperglycemia and increase insulin secretion in an animal model of type 2 diabetes. At diabetes onset, an ambulatory hyperglycemic clamp was performed. HDAC3 inhibition improved hyperglycemia over the study period without affecting weight gain. At the end of the hyperglycemic clamp, circulating insulin levels were significantly higher in BRD3308-treated animals. 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.
AB - 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. Here we tested the ability of a selective HDAC3 inhibitor, BRD3308, to reduce hyperglycemia and increase insulin secretion in an animal model of type 2 diabetes. At diabetes onset, an ambulatory hyperglycemic clamp was performed. HDAC3 inhibition improved hyperglycemia over the study period without affecting weight gain. At the end of the hyperglycemic clamp, circulating insulin levels were significantly higher in BRD3308-treated animals. 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.
U2 - 10.1111/dom.12470
DO - 10.1111/dom.12470
M3 - Letter
C2 - 25846481
VL - 17
SP - 703
EP - 707
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 7
ER -
ID: 135222112