Jetton Lab Research
Over the last several years Dr. Jetton's research has focused on the biology of tissues that regulate glucose homeostasis and pancreatic islet ß-cell growth and development.
The islets are richly vascularized "micro-organs" consisting of aggregates of five distinct peptide hormone-secreting cell types dispersed throughout the exocrine pancreas. Their principal function is blood glucose regulation. ß-cells have a significant capacity to compensate for increased insulin demands in response to somatic growth, pregnancy, normal periods of insulin resistance (e.g., puberty and aging), and pathological insulin resistance often associated with poor diet and lack of exercise. ß-cells compensate to the increased insulin requirements by enhancing their secretion of insulin and increasing their mass via several growth mechanisms. A failure of these adaptive mechanisms leads to type 2 diabetes.
The steady state mass of the ß-cells is determined by a dynamic balance of cell recruitment (via proliferation and "neogenesis"), individual cell growth, and cell death via apoptosis. We have generated several rodent models for studies that demonstrate
- ß-cell neogenesis (newly differentiated cells) occurs from pancreatic exocrine tissue and contributes significantly to rapidly increased ß-cell mass, and can be the prime means of short-term ß-cell growth
- the insulin signaling cascade via protein kinase B/Akt is a central mediator of ß-cell growth and survival processes
- selective pancreatic branch vagotomy interrupts ß-cell growth and survival signaling
Long-term research interests of the lab include:
- developmental and regeneration biology of pancreatic islets
- neural and dietary regulation of beta cell mass homeostasis
Our work has bearing on the future development of strategies to increase functional ß-cell mass in diabetic patients. There is now substantial interest in ß-cell replacement strategies for the future management of insulin-dependent diabetes. These strategies will require amplification of pancreatic islet tissue in vitro or ex vivo for transplantation, or inducing new islet tissue by stimulating their growth within the diabetic patient. Accordingly, a fundamental issue is to fully elucidate the mechanisms that regulate the development and the steady-state mass of ß-cells. Our current projects focus on
- identifying ß-cell progenitors and investigating the regulation of ß-cell growth and regeneration, and physiological adaptation in several animal models (with Drs. J. Leahy and M. Peshavaria)
- the neural control of ß-cell mass (with Drs. J. Leahy, M. Peshavaria, and D. Gupta)
- the nutritional regulation of ß-cell growth (with Dr. C.L. Kien).
We routinely use a wide variety of complementary analytical techniques including
- multiple-labeling confocal microscopy, immunoelectron microscopy, and laser capture microdissection
- morphometric and digital image analyses
- immunochemistry (immunoblot/ELISA) and quantitative PCR
- metabolic studies and measures of glucose homeostasis