The purpose of this subcontract is to support the experiments being conducted by my lab at Cornell to complete the work being funded by the Hartwell Foundation. The goal of the original proposal was to define and target a novel islet pathway that we previously identified in our mouse bariatric model for the treatment of diabetes. Specifically, our central hypothesis is that beta cell GLP-1R signaling increases alpha cell GLP-1 production to augment GSIS in a paracrine positive feedback loop. The goal of this grant is to identify and pharmaceutically target the secreted factor(s) responsible for the effect of beta cell GLP-1R signaling to increase alpha cell GLP- 1 production.

This work is divided into two aims:

Aim 1: Identify the secreted factor(s) responsible for the effect of beta cell GLP-1R signaling to increase
alpha cell PC1/3 expression.

Aim 2: Identify and develop a pharmaceutical strategy for enhancing alpha cell PC1/3 expression for
diabetes treatment.