Xinfu Guan, Ph.D.
Assistant Professor of Pediatrics, Baylor College of Medicine
Dr. Guan’s research goal is to understand the cellular and molecular mechanisms by which nutrients and hormones interact to control the gut development, growth, and function in the neonate. One of key nutrient-responsive gut neuropeptides is glucagon-like peptide 2 (GLP-2) that exerts diverse actions in the gastrointestinal tract including enhancing epithelial cell survival and proliferation, mucosal blood flow, nutrient uptake and metabolism, but suppressing gastric motility and secretion. In collaboration with Dr. Burrin, Dr. Guan has shown that GLP-2 acutely and dose-dependently induces intestinal blood flow via a nitric oxide-dependent neurogenic mechanism, and the protein expression of GLP-2 receptor is colocalized with vasoactive neurotransmitters in endocrine cells and neurons in the human and porcine small intestine. These findings suggest that key vasoactive neurotransmitters may participate via enteric neurons as GLP-2 receptor-transduced downstream signals in the regulation of intestinal blood flow, motility and mucosal epithelial growth and metabolism. Using molecular and cell biology approaches in combination in vivo metabolism methodology, Dr. Guan’s current focus is to define the physiological function and signaling hierarchy of GLP-2 receptor in novel genetically modified mouse models, which will establish whether GLP-2 receptor activation controls intestinal epithelial growth, absorptive function, and submucosal microcirculation under physiological conditions (e.g., in response to enteral nutrition) and in disease states (e.g., short bowel syndrome and total parenteral nutrition-induced epithelial atrophy). Insights from such studies will provide critical mechanistic information that may lead to development of GLP-2 as a therapeutic strategy to treat intestinal dysfunctions (e.g., necrotizing enterocolitis and short-bowel syndrome).
Another focus is to assess macronutrient metabolism and utilization from the whole-body to specific organ kinetics using stable isotope tracer technique. For example, Dr. Guan has applied and developed a stable isotope tracer technique coupled with arteriovenous organ balance and real-time blood flow measurement to quantify the intestinal uptake and metabolism of glucose and amino acids provided enterally or parenterally. These studies are aimed at establishing how these nutritional and hormonal factors modulate the rates of cellular protein turnover, proliferation and programmed cell death of mucosal epithelial cells, and physiological function of the gastrointestinal tract.
GUAN, X., H. E. Karpen, J. Stephens, J. T. Bukowski, S. Niu, G. Zhang, B. Stoll, M. J. Finegold, J. J. Holst, D. L. Hadsell, B. L. Nichols, and D. G. Burrin. 2006. GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow. Gastroenterology. 130: 150-164.
Horst, D. A., M. Sedenquist, B. Stoll, X. GUAN, K. Ellis, and D. G. Burrin. 2006. Glucagon-like peptide-2 does not affect bone metabolism in TPN-fed neonatal piglets. Pediatric Research. (Accepted).
Burrin, D. G., B. Stoll, X. GUAN, L. Cui, X. Chang, and D. L. Hadsell. 2006. GLP-2 rapidly activates divergent intracellular signaling pathways involved in intestinal cell survival and proliferation in neonatal piglets. Am. J. Physiol. Endocrinol. Metab. (Accepted).
Farmer, C., X. GUAN, and N. L. Trottier. 2006. Impacts of dietary protein level on mammary arteriovenous differences of plasma metabolic substrates and anabolic hormones in lactating sows. Domest. Anim. Endocrinol. (Accepted).
GUAN, X. and D. G. Burrin. 2005. “Methodological Approaches to Metabolism Research”. In: Biology of Metabolism in Growing Animals (Eds. DG. Burrin and HJ. Mersmann), London (United Kingdom): Elsevier Science B. V. Publishers, pp. 435-477.
Bos, C., B. Stoll, H. Fouillet, C. Gaudichon, X. GUAN, M. A., Grusak, P. J. Reeds, D. Tome, and D. G. Burrin. 2005. Postprandial intestinal and whole-body nitrogen kinetics and distribution in piglets fed a single. Am. J. Physiol. Endocrinol. Metab. 288: E436-46.
Burrin, D. G., B. Stoll, X. GUAN, L. Cui, X. Chang, and J. J. Holst. 2005. GLP-2 dose-dependently activates intestinal cell survival and proliferation in neonatal piglets. Endocrinology. 146: 22-32.
Niinikoski, H., B. Stoll, X. GUAN, K. Kansagra, B.D. Lambert, J. Stephens, B. Hartmann, J. J. Holst, and D.G. Burrin. 2004. Onset of small intestinal atrophy is associated with reduced intestinal blood flow in TPN-fed neonatal piglets. J. Nutr. 134: 1467-1474.
GUAN, X., B. J. Bequette, P. K. Ku, R. J. Tempelman, and N. L. Trottier. 2004. The amino acid need for milk synthesis is defined by the maximal uptake of plasma amino acids by porcine mammary glands. J. Nutr. 134: 2182-2190.
GUAN, X., J. E. Pettigrew, P. K. Ku, N. K. Ames, B. J. Bequette, and N. L. Trottier. 2004. Dietary protein concentration affects plasma arterio-venous difference of amino acids across the porcine mammary gland. J. Anim. Sci. 82(10):2953-2963.
GUAN, X., B. Stoll, X. Lu, K. Tappenden, J. J. Holst, B. Hartman, and D. Burrin. 2003. GLP-2-mediated upregulation of intestinal blood flow and glucose uptake is nitric-oxide-dependent in TPN-fed piglets. Gastroenterology. 125: 136-147.
Burrin, D., X. GUAN, B. Stoll, Y. M. Petersen, and P. T. Sangild. 2003. Glucagon-like peptide 2: a key link between nutrition and intestinal adaptation in neonates? J. Nutr. 133: 3712-3716.
Bos, C., B. Stoll, H. Fouillet, C. Gaudichon, X. GUAN, M. A., Grusak, P. J. Reeds, D. Tome, and D. G. Burrin. 2003. Intestinal lysine metabolism is driven by the enteral availability of dietary lysine in piglets fed a bolus meal. Am. J. Physiol. Endocrinol. Metab. 285:E1246-E1257.
Burrin, D. G., B. Stoll, and X. GUAN. 2003 Glucagon-like peptide-2 function in the gut. Domest. Anim. Endocrinol. 24:103-122.
GUAN, X., B. J. Bequette, G. Calder, P. K. Ku, K. N. Ames, and N. L. Trottier. 2002. Amino acid availability affects amino acid flux and protein metabolism in the porcine mammary gland. J. Nutr. 132:1224-1234.
GUAN, X., J. J. Matte, J. L. Snow, P. Ku, J. Burton, and N. L. Trottier. 2000. High-chromium yeast supplementation improves glucose tolerance by decreasing hepatic extraction of insulin in pigs. J. Nutr. 130:1274-1279.
Trottier, N. L. and X. GUAN. 2000. Research paradigms behind amino acid requirements of the lactating sow: Theory and applications. J. Anim. Sci. 78(Suppl. 3): 48-58.
GUAN, X., J. E. Pettigrew, P. K. Ku, N. K. Ames, B. J. Bequette, and N. L. Trottier. 2005. Dietary protein concentration and lactation stage determine plasma amino acid uptake profile across the porcine mammary gland. (In preparation).