Sean W Limesand

Sean W Limesand

Professor, Animal and Comparative Biomedical Sciences
Professor, Physiological Sciences - GIDP
Director, Agriculture Research Complex
Professor, Obstetrics and Gynecology
Chair, Institutional Animal Care-USE Committee
Professor, BIO5 Institute
Department Affiliations
Contact
(520) 626-8903

Work Summary

Our current research program use an integrative approach at the whole animal, isolated organ, cellular and molecular levels to investigate developmental adaptations in pancreatic β-cells and insulin sensitivity that result from early life risk factors, such as intrauterine growth restriction, and increase risk of glucose intolerance and Diabetes in later life.

Research Interest

Sean W. Limesand, PhD, is an Associate Professor in the School of Animal and Comparative Biomedical Sciences at the University of Arizona in the College of Agriculture and Life Sciences. He is also a member of the UA’s BIO5 Institute and Department of Obstetrics and Gynecology. Dr. Limesand is nationally and internationally recognized for his work studying fetal endocrinology and metabolism in pregnancy and in pregnancies compromised by pathology such as intrauterine growth restriction and diabetes. His research is focused on defining developmental consequences resulting from a compromised intrauterine environment. Specifically, he is focused on fetal adaptations in insulin secretion and action that when altered in utero create lifelong metabolic complications. Dr. Limesand has lead the charge on prenatal origins of –cell dysfunction as the Principal Investigator for a number of federal and foundation grant awards and published more than 40 peer-reviewed articles on topics related to this research. Keywords: Diabetes, Pregnancy, Perinatal Biology

Publications

Limesand, S. W., Rozance, P. J., Smith, D., & Hay Jr., W. W. (2007). Increased insulin sensitivity and maintenance of glucose utilization rates in fetal sheep with placental insufficiency and intrauterine growth restriction. American Journal of Physiology - Endocrinology and Metabolism, 293(6), E1716-E1725.

PMID: 17895285;Abstract:

In this study we determined body weight-specific fetal (umbilical) glucose uptake (UGU), utilization (GUR), and production rates (GPR) and insulin action in intrauterine growth-restricted (IUGR) fetal sheep. During basal conditions, UGU from the placenta was 33% lower in IUGR fetuses, but GUR was not different between IUGR and control fetuses. The difference between glucose utilization and UGU rates in the IUGR fetuses demonstrated the presence and rate of fetal GPR (41% of GUR). The mRNA concentrations of the gluconeogenic enzymes glucose-6-phophatase and PEPCK were higher in the livers of IUGR fetuses, perhaps in response to CREB activation, as phosphorylated CREB/total CREB was increased 4.2-fold. A hyperglycemic clamp resulted in similar rates of glucose uptake and utilization in IUGR and control fetuses. The nearly identical GURs in IUGR and control fetuses at both basal and high glucose concentrations occurred at mean plasma insulin concentrations in the IUGR fetuses that were ∼70% lower than controls, indicating increased insulin sensitivity. Furthermore, under basal conditions, hepatic glycogen content was similar, skeletal muscle glycogen was increased 2.2-fold, the fraction of fetal GUR that was oxidized was 32% lower, and GLUT1 and GLUT4 concentrations in liver and skeletal muscle were the same in IUGR fetuses compared with controls. These results indicate that insulin-responsive fetal tissues (liver and skeletal muscle) adapt to the hypoglycemic-hypoinsulinemic IUGR environment with mechanisms that promote glucose utilization, particularly for glucose storage, including increased insulin action, glucose production, shunting of glucose utilization to glycogen production, and maintenance of glucose transporter concentrations. Copyright © 2007 the American Physiological Society.

Davis, M., Brown, L., Wai, S., Wesolowski, S., Limesand, S., & Rozance, P. (2016). Chronic Amino Acid Supplementation Increases Beta-Cell Mass, Islet Area, and Pancreatic Vascularization in Growth Restricted Fetal Sheep.. REPRODUCTIVE SCIENCES, 23, 150A-150A.
Steyn, L. V., Ananthakrishnan, K., Anderson, M. J., Patek, R., Kelly, A., Vagner, J., Lynch, R. M., & Limesand, S. W. (2015). A Synthetic Heterobivalent Ligand Composed of Glucagon-Like Peptide 1 and Yohimbine Specifically Targets β Cells Within the Pancreas. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.
BIO5 Collaborators
Sean W Limesand, Ronald M Lynch

β Cell specificity for a heterobivalent ligand composed of glucagon-like peptide-1 (GLP-1) linked to yohimbine (GLP-1/Yhb) was evaluated to determine its utility as a noninvasive imaging agent.

Limesand, S., Grundmann, O., Mitchell, G. C., & Limesand, S. W. (2009). Sensitivity of salivary glands to radiation: from animal models to therapies. Journal of dental research, 88(10).

Radiation therapy for head and neck cancer causes significant secondary side-effects in normal salivary glands, resulting in diminished quality of life for these individuals. Salivary glands are exquisitely sensitive to radiation and display acute and chronic responses to radiotherapy. This review will discuss clinical implications of radiosensitivity in normal salivary glands, compare animal models used to investigate radiation-induced salivary gland damage, address therapeutic advances, and project future directions in the field.

Hill, M. G., Kelly, A. C., Camp, S. M., Reed, K. L., Limesand, S. W., & Garcia, J. (2016). Increased Glucagon and Decreased Visfatin Concentrations in the Cord Blood of Fetuses from Type I Diabetic Patients.. REPRODUCTIVE SCIENCES, 23, 140A-140A.