Dr. Jetton received his PhD in Biology from Vanderbilt University in 1990. Following his postdoctoral research in diabetes and pancreatic ß-cell biology in the Department of Molecular Physiology and Biophysics at the Vanderbilt School of Medicine, he was recruited to a junior faculty position and was Coordinator of Vanderbilt's first Imaging Core facility. He joined UVM's Department of Medicine in 1999. His current research focuses on neural and dietary regulation of ß-cell mass homeostasis.

My research over the last several years 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 due to somatic growth, pregnancy, periods of insulin resistance (e.g., pregnancy and aging), and lack of exercise. ß-cells compensate to the increase insulin requirements by enhancing their secretion of insulin and increasing their mass via several growth mechanisms.

The steady state mass of the ß-cell is determined by a dynamic balance of cell recruitment (via proliferation and “neogenesis”), individual cell growth (hypertrophy), and cell death via apoptosis. Over the past few years we have generated several rodent models whose studies have led us to suggest that (1) ß-cell neogenesis occurs from pancreatic exocrine tissue, (2) “neogenic” cells contribute significantly to the rapidly increased ß-cell mass, (3) neogenesis can be the prime means of ß-cell growth, and (4) the insulin signaling cascade via protein kinase B/Akt is a central mediator of these ß-cell growth processes. Thus, our studies have shown that Akt signaling likely controls ß-cell proliferation, survival, cellular growth, and neogenesis.

All of the islet cell types, including the predominant insulin-secreting ß-cell, are thought to originate from pluripotent progenitor cells during embryonic development. These precursor cells are associated with the primitive pancreatic duct epithelium and undergo a series of differentiation steps that give rise to cells with distinct endocrine phenotypes. However, in adult life, the primary means of ß-cell growth in mice is thought to rely on proliferation of pre-existing ß-cells. The extent to which new ß-cells in the adult animal may develop from pancreatic epithelial progenitors (“neogenesis”) is a contentious subject and likely depends on the model under study. Importantly, there is mounting evidence that, in humans, neogenesis is an ongoing process throughout life. Hence, the nature and existence of an adult pancreatic “stem cell” remains obscure. While mature islet cells are well characterized, islet stem or progenitor cells, and the factors that control their differentiation, have yet to be adequately defined.

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 induction of new islets 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. We routinely use a wide variety of analytical techniques including multiple-labeling confocal microscopy, immunoelectron microscopy, digital image analyses, laser capture microdissection, immunochemistry, and qPCR to resolve the mechanisms underlying β-cell growth and mass homeostasis, as well as to identify the expression of known and novel genes and their roles during islet neogenesis.

Current Principal Research Projects

A recent interest in our lab is the CNS control over ß-cell mass homeostasis. We have developed a surgical technique whereby the parasympathetic innervation to the pancreas can be interrupted without perturbing gut motility. It appears that the CNS exerts a tonic effect on ß-cell growth in normal animals. We are investigating the roles of the CNS in animal models with enhanced adaptive ß-cell growth.

Lausier J, Diaz WC, Roskens V, LaRock K, Herzer K, Fong CG, Latour MG, Peshavaria M, Jetton TL.Vagal control of pancreatic ß-cell proliferation. Am J Physiol Endocrinol Metab. 2010 Nov;299(5):E786-93.

Jetton TL, Everill B, Lausie Jr, Roskens V, Habibovic A, LaRock K, Gokin A, Peshavaria M, Leahy JL Enhanced ß-cell mass without increased proliferation following chronic mild glucose infusion. Am J Physiol Endocrinol Metab 2008 294:E679-87.

Peshavaria M, Larmie BL, Lausier J, Satish B, Habibovic A, Roskens V, LaRock K, Everill B, Leahy JL, and Jetton TL Regulation of pancreatic ß-cell regeneration in the normoglycemic 60 % partial pancreatectomy mouse. Diabetes 2006 55 (12): 3289-3298.

Jetton TL, Lausier J, LaRock K, Trotman WE, Larmie B, Habibovic A, Peshavaria M, Leahy JL Mechanisms of compensatory ß-cell growth in insulin resistant rats: Roles of Akt kinase. Diabetes 2005 54:2294-304.

* indicates equal contribution