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Project Abstracts - CTAR

Neuromodulation for Type 1 Diabetes: Harnessing Sensory Innervation to Promote Regeneration and Function of Insulin-Producing Cells.

Contact PI: Abdelfattah El Ouaamari, PhD

Abstract

The failure to maintain an adequate number of functional pancreatic islet insulin-secreting β cells is a shared trait of all forms of diabetes, including type 1 and type 2 diabetes. Neuromodulation is an emerging field in biomedicine for the treatment of chronic conditions. However, the therapeutic specificity of this approach remains poorly defined because of the lack of the molecular blueprint of the peripheral efferent and afferent fibers innervating the targeted viscera. In the context of diabetes, the identification and characterization of the neurons projecting in the vicinity of insulin-producing β cells can lead to the development of selective neuronal-based methods to restore β-cell mass and/or activity. We propose to use trans-synaptic tracing and RNA-Seq techniques to dissect the genetic identity of pancreas-specific projecting neurons. Using immunofluorescence techniques, we will verify the presence of identified mouse pancreatic neurons in human pancreata derived from heart-beating individuals with or without diabetes. Finally, we will use chemogenetic approaches to enhance functional β-cell mass through neuromodulation of pancreas-projecting nerve fibers. The long-term goal of these studies is to identify neuronal signals that can be leveraged to prevent, delay and/or even treat diabetes.