Type 2 diabetes mellitus (T2DM) is a chronic disease of epidemic proportions that is marked by insulin resistance and progressive loss of beta cell number and function. This relative insulinopenia results from a combination of beta cell dysfunction and loss of beta cell mass. Obesity is a major driver of T2DM. More than half of the patients with T2DM are obese and 86% are considered overweight or obese. Adipose tissue function and dysfunction have thus been intimately linked to the development and progression of T2DM. In our NIH funded K08 award, we identified the adipokine adipsin, which is reduced in obesity, as a critical regulator of pancreatic beta cell failure in murine models of T2DM. In this proposal, we seek to follow up on these studies and assess the possibility that prolonged adipsin treatment may be a good therapy for chronic diabetes. The proposed work will involve both in vitro experiments using pancreatic islets and in vivo analyses of mice in a type 2 diabetic model with beta cell insufficiency. We will pursue the following specific aims: 1. Determine how the adipsin/C3a pathway protects against pancreatic beta cell failure in a model of type II diabetes mellitus with beta cell failure. 2. Determine the mechanism of action of C3a-mediated protection of islet cells from cell death. These studies will shed light on novel adipose-pancreatic pathways that may ultimately lead to new treatment options for T2DM.

Public Health Relevance

Type 2 diabetes mellitus (T2DM) is a chronic disease of epidemic proportions that is marked by insulin resistance and progressive loss of beta cell number and function. Presently no therapies exist for restoring beta cell function and numbers for T2DM patients once beta cell failure has ensued. In our proposal, we seek to develop new therapies that can be used to treat or reverse pancreatic beta cell failure in T2DM.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Research Grants (R03)
Project #
5R03DK111762-02
Application #
9416110
Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
Program Officer
Spain, Lisa M
Project Start
2017-02-01
Project End
2019-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065