News & Research

    Cornell University, Ithaca, New York

Regulation of systemic insulin sensitivity by adipocyte XBP1s

General Research Subject: Type 2 Diabetes

Focus: Adipocytes, Insulin Action\Transgenic Models, Integrated Physiology\Insulin Resistance

Type of Grant: Career Development

Project Start Date: January 1, 2012

Project End Date: December 31, 2014

Diabetes Type: Type 2 diabetes

Research Description

As a growing obesity epidemic paralleled by an increased incidence of type 2 diabetes are threatening the health of millions of Americans, a better understanding of the basic pathways linking obesity and insulin resistance is critical to the development of new therapeutic approaches. Excitingly, our preliminary data using a gain-of-function mouse model suggest that the spliced form of X-box-binding protein 1 (XBP1s), a key transcription factor of the mammalian unfolded protein response (UPR), may act as an important regulator of the folding and secretion of adiponectin, an insulin-sensitizing cytokine released by adipocytes. The successful completion of this proposal may not only delineate a novel role of XBP1s in systemic insulin sensitivity, but also identify regulators of XBP1s as novel drug targets in increasing circulating adiponectin levels and promoting systemic insulin sensitivity.

Research Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

As a growing obesity epidemic paralleled by an increased incidence of type 2 diabetes threaten the health of millions of Americans, our project aims for a better understanding of the basic pathways linking obesity and insulin resistance. This effort is critical for the development of new therapeutic approaches. Excitingly, our preliminary data using a gain-of-function mouse model suggest that the spliced form of X-box-binding protein 1 (XBP1s), a key transcription factor of the mammalian unfolded protein response (UPR), may act as an important regulator of the folding and secretion of adiponectin, an insulin-sensitizing cytokine released by adipocytes. Thus, the successful completion of this proposal may not only delineate a novel role of XBP1s in systemic insulin sensitivity, but also identify regulators of XBP1s as novel drug targets in increasing circulating adiponectin levels and promoting systemic insulin sensitivity.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

Adiponectin is an important adipokine involved in the regulation of insulin resistance and energy homeostasis, and hence, plays a critical role in metabolic and cardiovascular diseases. Its biological activity is closely linked to its folding, multimerization and secretion processes by adipocytes. As extensive efforts have been and are being made to elevate adiponectin levels in treating metabolic syndrome, our study has the potential to identify a novel regulator of adiponectin folding and secretion. As defects in adiponectin multimerization and secretion are associated with hypoadiponectinemia and hyperglycemia in humans, our study may have significant therapeutic implications.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

Obesity and its-associated complications such as type-2 diabetes and heart diseases are among one of the top killers in the Western society. I have witnessed some of my friends and relatives who are suffering from it. Thus, as a scientist, I feel the urgency to find a feasible strategy to prevent, diagnose and treat diabetes. The Career Development Award from ADA is the recognition of our work in the last 5 years, and will play a key role in the efforts to further establish my research program in obesity and diabetes research. Receipt of this award will give me the time, resources and confidence to explore projects that are directly relevant to the goals of the ADA.

In what direction do you see the future of diabetes research going?

Towards a very detailed molecular understanding of interplay between the endocrine system and other systems, most notably, the immune system, using a combination of the state-of-the-art biochemical, immunological and physiological approaches, and moreover, towards a very detailed cellular understanding of the role of various cellular organelles and transcription factors in the pathogenesis of obesity and type-2 diabetes, using a combination of the state-of-the-art biochemical, cell biological and physiological approaches.