Aims to identify how the neuropeptide galanin regulates the physiology and adaptation of pancreatic islets under healthy and diabetic states.

The project aims to identify how the neuropeptide galanin regulates the physiology and adaptation of pancreatic islets under healthy and diabetic states. Hormones released from pancreatic islets (including insulin from beta cells and glucagon from alpha cells) are critical for maintaining glucose homeostasis and losing this regulation leads to diabetes and its many co-morbidities. The loss of functional beta cell mass is a hallmark of both type 1 and type 2 diabetes. Harnessing the endogenous beta cell pool to slow the progression or reverse the disease would require treatment strategies to (1) expand beta cell mass, (2) increase beta cell function, and (3) prevent beta cell death. Various neural signals have demonstrated the ability to promote organ development and coordinate complex organ function. While galanin signalling has been implicated in islet hormone release in mammalian models, the cellular and molecular mechanisms underlying endogenous galanin control of islet homeostasis remains understudied. These fundamental studies require the use of live animal models where galanin signalling can be tightly controlled and islet biology can be dynamically studied. By taking advantage of the zebrafish, we will optogenetically manipulate pancreatic galanin nerves and investigate how altering galanin signalling impacts islet physiology and beta cell regeneration with precision on physiological time scales in a living animal. In our complementary investigation of galanin nerve remodelling in human pancreas samples from non-diabetic and diabetic donors, we will assess the translatability of our findings to humans. Understanding how galanin controls islet biology and identifying how galanin nerves are perturbed in diabetes may lead to new therapeutic approaches to preserving the functionality of residual islet cells and expanding the beta cell pool in diabetes.