Novel Target for the Treatment of Type 2 Diabetes

Understanding obesity's role in the development of type 2 diabetes

Full Project Name:Novel Target for the Treatment of Type 2 DiabetesPrincipal Investigator:Nancy M. Dahms, PhD, BiochemistryCo-Investigator:Srividya Kidambi, MD, Medicine; Rebecca Gundry, PhD, BiochemistryAward Amount:$2,000

Award Date

July2015

Project Duration:24 months

Project Description Narrative:

Wisconsin has the 22nd highest adult obesity rate in the United States at almost 30%, a dramatic increase from 12 percent in 1990. Obesity increases the risk of a number of serious health issues including heart disease, dementia and type 2 diabetes.

Type 2 diabetes is the seventh leading cause of death in the nation, and affects more than 475,000 adults in Wisconsin. The disease costs the state $6.1 billion annually in health care costs and lost productivity. Approximately one-third of patients develop type 2 diabetes due to obesity. The remaining two-thirds of individuals retain the ability to produce and respond to insulin in order to normally process food.

By better understanding this phenomenon, investigators aim to advance knowledge and design new approaches to delay or prevent the onset of type 2 diabetes due to obesity.

Outcomes & Lessons Learned:

Discovered that a key enzyme plays a significant role in protecting insulin-producing cells in the pancreas by preventing an accumulation of free fatty acids. If free fatty acids build up to significant levels, the resulting chemical environment can become toxic and even deadly to the cell
Identified the feasibility, reproducibility, and sensitivity of a targeted mass spectrometry approach for the detection of a low abundant protein (i.e., PPT1) in human biopsied tissues
Demonstrated that PPT1 levels are higher in adipose tissues from metabolically healthy non-obese and obese individuals compared to diabetic obese individuals. A similar trend was observed for another lysosomal protein, LAMP1
Identified results that support a novel role of the lysosome and its degradative enzyme, PPT1, in protecting individuals from developing Type 2 Diabetes
Generated new knowledge about how certain fatty acids harm insulin-producing cells, as well as about the enzyme that maintains a healthy level of fatty acids, the investigators will be better able to design new approaches to delay or prevent the onset of type 2 diabetes due to obesity