Dr. Sean Limesand
Agricultural Research Center
4101 North Campbell Ave
Tucson, AZ 85719
Phone: (520) 626-8903
Fax: (520) 626-1283
- Ph.D., Colorado State University
- M.S. Colorado State University
- B.S. North Dakota State University
- ANS 587 - Molecular Endocrinolgy
Dr. Sean Limesand joined the Animal Sciences Department in 2005. Prior to joining the UA he worked at the University of Colorado Health Sciences Center as a Postdoctoral Fellow in the Department of Pediatrics and later as an Instructor in the Department of Pediatrics. Dr. Limesand's graduate studies focused mainly on fetal growth and development in sheep, specifically how abnormal fetal nutrition influences the formation and function of the pancreas. He continues his study of the endocrine system and Type 2 Diabetes at the U of A, primarily through sheep trials.
Some of the most debilitating diseases affecting public health and those that impose an extreme monetary impact on health care costs in the United States are metabolic diseases and endocrine disorders such as Type 2 Diabetes. The prevalence of these diseases in the USA has been growing faster than Mendelian inheritance rates suggesting that environmental cues are influencing the prevalence of adulthood metabolic disorders. Inappropriate fetal growth and development due to inadequate fetal nutrition has been associated with several adult onset diseases including diabetes (Barker Hypothesis). Pancreatic b-cells secrete the anabolic hormone, insulin, in response to nutrient changes during the second half of gestation, likely coordinating fetal growth rate with fetal nutrient supply, making the fetal b-cell a potential target for nutritional adaptation in utero.
To understand nutrient regulation of fetal pancreas development, I am studying how poor fetal nutrition reduces pancreas formation and function. Environmental stress during pregnancy in sheep causes placental insufficiency; thus, creating an inadequate fetal nutrient supply that leads to fetal growth restriction and impaired insulin secretion due to decreased b-cell number and function. Current research aims are designed to determine mechanism that reduced cell responsiveness in intrauterine growth restricted fetuses.
The first aim is to determine stages of pancreatic development and endocrine cell replication in this large animal model to understand how b-cell numbers are reduced. In addition to a lower number of cells, their stimulus secretion coupling is impaired due to reduced insulin production. Therefore, the second aim is to determine deficits in insulin biosynthesis. If these inadequacies shown in the growth restricted fetus are not compensated for after birth, they might persist into adulthood and contribute tofailure of insulin secretion to predispose offspring to Type 2 Diabetes.
- Limesand SW, Jensen J, Hutton JC, Hay WW Jr. May 2005. Diminished beta-cell replication contributes to reduced beta-cell mass in fetal sheep with intrauterine growth restriction. Am J Physiol Regul Integr Comp Physiol, 288:R1297-305
- Limesand SW, Rozance PJ, Zerbe GO, Hutton JC, Hay WW Jr. 2006. Attenuated Insulin Release and Storage in Fetal Sheep Pancreatic Islets with Intrauterine Growth Restriction. Endocrinology, 147(3): 1488-1497.
- Limesand, SW., P.J. Rozance, L.D. Brown, W.W. Hay, Jr. 2009. Effects of Chronic Hypoglycemia and Euglycemic Correction on Lysine Metabolism in Fetal Sheep. Am J Physiol Endocrinol Metab. 296(4): E879-887.
- Cole, L., M.J. Anderson, P.B. Antin, S.W. Limesand. 2009. One Process for Pancreatic β-cell Coalescence into Islets Involves an Epithelial-Mesenchymal Transition. Journal of Endocrinology, 203(1):19-31.
- Leos, R.A., X. Chen, M.J. Anderson, J.P. Evans, K.A. Anderson, and S.W. Limesand. Chronic exposure to elevated norepinephrine suppresses insulin secretion in fetal sheep with placental insufficiency and intrauterine growth restriction. Am J Physiol Endocrinol Metab. 298: 2010.
- Miranda Anderson - Research Specialist
Animal Research Center
4101 N. Campbell Ave.