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Histone Deacetylase 3 Inhibition Improves Glycaemia and Insulin Secretion in Obese Diabetic Rats

Histone Deacetylase 3 Inhibition Improves Glycaemia and Insulin Secretion in Obese Diabetic Rats

M Lundh, T Galbo, S S Poulsen, T Mandrup-Poulsen

Diabetes Obes Metab. 2015 Jul;17(7):703-7.

PMID: 25846481

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1550053025	BRD3308		1550053-02-5	Price

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