Promising Epigenetic Drug Target for Diabetes

Newswise — A new research report published in the November 24 issue of the Clinical Epigenetics, suggests that epigenetic mechanism based drugs could become one of the treatment armamentarium of future anti-diabetic agents. It appears that epigenetic alterations like histone modifications play significant role in the genesis of type 2 diabetes and its complications than previously believed. Specifically, histone deacetylase-3 (HDAC3), one of the epigenetic signatures, reported to be increased in patients with type 2 diabetes with an association of proinflammation, poor glycemic control and insulin resistance. Targeting HDAC3 might be an effective treatment strategy for type 2 diabetes.

"Targeting epigenetic pathways would be the way for future anti-diabetic drugs with novel mode of actions and newer therapeutic options”, said Muthuswamy Balasubramanyam, Dean of Research Studies & Senior Scientist from the Madras Diabetes Research Foundation in Chennai, India. “Although a role for of histone deacetylases (HDAC) in metabolic disorders has been known and HDAC inhibitors worked well in the preclinical studies, this is the first-time in the clinical diabetes setting, we have shown augmentation of histone deacetylase-3 (HDAC3) in cells from patients with type 2 diabetes” he added.

Aberrant epigenetic modifications such as DNA methylation, histone modification, and microRNA alterations are well recognized drivers for the cancer phenotype, but the accumulating evidence also imply their role in the etiology of diabetes and cardiovascular diseases. Even during mild dysglycemia, epigenetic imprints start operating in our cells and body and they are the upstream signaling masters that influence several of the stress signaling alterations linked to diabetes and its complications. Study from the Madras Diabetes Research Foundation identified one such epigenetics signatures HDAC-3, as a novel drug target. “In support of our significant clinical finding, in a recent transgenic mice model work from USA, HDAC3 deletion of histone deacetylase 3 in adult beta cells has been shown to improve glucose tolerance via increased insulin secretion” said Balasubramanyam.

“Now we are also moving on the direction to check whether we could identify and validate potential HDAC3 inhibitors from the Ayurvedic Treasure of India” adds Balasubramanyam. While the benefits of physical exercise on type 2 diabetes and prevention and control is well conceived, there is also a potential avenue to check whether the beneficial metabolic changes of lifestyle modification (both exercise and yoga) can occur through epigenetic alterations like histone modifications. “The work from MDRF1 represents an interesting advancement in identification of HDAC3 as a novel drug target from the epigenetic pathways for the expansion of therapeutic options for type 2 diabetes” said Balasubramanyam.

Journal Reference:C.Sathishkumar, P.Prabu, M.Balakumar, R.Lenin, D.Prabu, R.M.Anjana, V.Mohan, M.Balasubramanyam. Augmentation of histone deacetylase 3 (HDAC3) epigenetic signature at the interface of proinflammation and insulin resistance in patients with type 2 diabetes. Clin Epigenetics. 2016 Nov 24;8:125. DOI:10.1186/s13148-016-0293-3

Dr.M.Balasubramanyam, PhD., MNASc., FAPAScDean of Research Studies & Senior ScientistMadras Diabetes Research Foundation (MDRF)4, Conran Smith Road, GopalapuramChennai - 600086,  India