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Samuel Stephens, PhD

Assistant Professor
Internal Medicine

Office: 3334 PBDB
Office Phone: 319-335-4843

Lab: 3400 PBDB

Lab Website: https://stephens.lab.uiowa.edu/

Mechanisms regulating pancreatic islet cell function and survival

The regulated release of the pancreatic islet hormones glucagon and insulin from α- and β-cells, respectively, coordinates metabolic fuel homeostasis. Inappropriate islet hormone release, including insulinopenia due to loss of β-cell function and mass, and hyperglucagonemia from dysregulation of α-cell function conspires with insulin resistance to cause sustained hyperglycemia and the development of Type 2 diabetes (T2D). Multiple factors may contribute to the deterioration of islet cell function in T2D, including genetic predisposition, gluco-lipotoxicity, increased secretory demand, ER and oxidative stress, and inflammatory cytokines. Regardless of the destructive mechanism, maintenance of functional β-cell mass is recognized as a key strategy for delaying and/or preventing development of T2D.

My laboratory is focused on understanding factors that regulate pancreatic islet β-cell function and survival. My work explores the actions of the islet derived prohormone VGF, which functions intracellularly to promote secretory granule biogenesis, and extracellularly as an insulin secretagogue. Current projects include: 1) We are exploring the requirements of endogenous VGF for islet cell function and survival. We are using combined cell biological and ultrastructural techniques to explore the role of pro-VGF in maintaining granule integrity and facilitating secretory granule maturation. 2) Using animal models, we are investigating the requirement(s) of islet-derived VGF function for regulating glucose homeostasis. 3) Our past work has examined the utility of VGF peptides, such as TLQP-21, in promoting islet cell function and survival. Here we are using gain-of-function and loss-of-function studies in animal models and cell culture to investigate the signaling mechanisms (receptors) underlying VGF peptide(s) function(s). 4) In a separate line of study, we are investigating endogenous mechanisms of adaptation used by islet cells to mitigate stress and promote survival. Understanding these pathways could have considerable value for the development of novel strategies to limit β-cell loss and promote β-cell recovery.

PubMed link

Department/Program Affiliations:
Internal Medicine
Molecular Medicine