Samuel Stephens, PhD

Assistant Professor
Internal Medicine

Mechanisms contributing to the loss of nutrient-regulated insulin secretion from pancreatic islet beta-cells in diabetes


The regulated release of the pancreatic islet hormones glucagon and insulin coordinate changes in nutrient availability during fasting/feeding to maintain whole animal nutrient status.  Chronic dysregulation of islet hormone release and loss of islet cell mass result in persistent hyperglycemia and the development of diabetes.  My research is focused on understanding fundamental aspects of islet cell function and survival with the long-term strategy of restoring normal (appropriate) islet hormone release as an effective diabetes treatment.  My laboratory explores 4 broad topic areas relevant to the pancreatic islet as follows: (i) understand the molecular mechanisms responsible for the fidelity of insulin secretory granule formation; (ii) explore the mechanisms contributing to dysregulation of secretory granule biogenesis in the context of human diabetes; (iii)  examine the generation of mitochondrial-derived coupling factors necessary to sustain fuel-stimulated insulin secretion; and (iv) investigate cell survival mechanisms utilized by pancreatic islets to circumvent apoptosis and promote cell recovery in the context of islet dysfunction.  To do this, we take a multi-disciplinary approach using genetic mouse models, ex vivo (rodent and human) islet cell culture, pharmacological tools, and cellular and molecular biology. 

Research areas
  • Gene Expression
  • Transcription and Regulatory Networks
  • Gene Therapy
  • Molecular Genetics