ABSTRACT

The primary molecular pathogen contributing to cardiac dysfunction in type-2 diabetes mellitus (T2DM) patients.

Full Description

Cardiac dysfunction is the leading cause of death (> 50%) in diabetic and pre-diabetic population. However, the specific molecular mechanisms underlying diabetic heart failure remain largely unknown. To date, there is no heart failure diagnostic method or treatment specific to diabetes, even though diabetic heart failure has a poor prognosis. Researchers at University of California, Davis have indentified the islet amyloid polypeptide (IAPP) oligomer, a toxic entity causally implicated in dysfunction of pancreatic β-cells and development of type-2 diabetes mellitus (T2DM), as the primary molecular pathogen linking T2DM to heart failure. UC Davis researchers have discovered that secretory dysfunction of pancreatic β-cells leading to the formation of IAPP toxic oligomers results in a feed forward process, whereby the secretion of these toxic entities in the blood causes additional damage in organs other than pancreas, including heart and kidneys. Thus, these toxic oligomers represent pathogens of diabetic cardiac dysfunction. Researchers have shown that accumulation of IAPP toxic oligomers in the heart triggers a cascade of structural and physiological changes within myocytes culminating in heart failure. The discovery that the IAPP toxic oligomer is a biomarker of heart failure in T2DM has immediate relevance in the diagnosis and prognosis of cardiac dysfunction in T2DM and pre-diabetic patients.

The UC Davis researchers’ findings reveal that the toxicity associated with accumulation IAPP oligomers in the heart manifests starting from early pre-diabetes. Thus, these oligomers may represent an effective target for diagnostic purposes and therapeutic strategies.

Applications

These findings have immediate relevance for individuals susceptible to develop cardiac dysfunction in pre-diabetes, when this biomarker has increased propensity to form and accumulate in the heart. These individuals can benefit from improved prognosis and development of new treatments.

Patent Status

Patent Pending

Features/Benefits

• Novel Diabetic Cardiomyopathy Diagnostics
• Targeted Therapies

Related Materials

• Hyperamylinemia Contributes to Cardiac Dysfunction in Obesity and Diabetes. A Study in Humans and Rats. Sanda Despa et al. - 01/24/2012
• THE ISLET AMYLOID POLYPEPTIDE TOXIC OLIGOMER IS A BIOMARKER OF HEART OR KIDNEY FAILURE IN TYPE-2 DIABETES MELLITUS. WO/2011/156389. - 12/15/2011

Inventors

• Bers, Donald M.
• Despa, Florin
• Despa, Sanda

Other Information

Contact

Nancy E. Rashid / nerashid@ucdavis.edu / tel: View Phone Number. Please reference Tech ID #20953.

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