IGPNS Faculty Mentors
Denise M. Ney, Ph.D.
Billings-Bascom Professor of Nutritional Sciences
2013 Rare Disease Hero Award, FDA
2012 Robert G.F. and Hazel T. Spitze Land Grant Faculty Award for Excellence
2010 Spitzer Excellence in Teaching Award
2000 Vilas Associate, Graduate School, UW-Madison
1995 BioServ Award, American Institute of Nutrition
B.S. 1975, University of California-Davis
Ph.D. 1986, University of California-Davis
Registered Dietitian and Certified Dietitian
Principal Research Interest
Gastrointestinal physiology and nutritional management of phenylketonuria.
This laboratory studies intestinal adaptation in controlled feeding systems, including total parenteral nutrition (TPN) in rats and transgenic mice. The goal of our research is to determine the mechanisms of nutrient-hormone interactions during intestinal adaptation with an emphasis on glucagon like peptide-2 (GLP-2) and insulin-like growth factor-I (IGF-I).
Nutritional Management of Phenylketonuria.
Our research group has conducted studies in subjects with phenylketonuria (PKU) that establishes the acceptability and safety of foods made with the whey protein, glycomacropeptide, in the nutritional management PKU. PKU is a genetic disorder caused by deficiency of hepatic phenylalanine hydroxylase that converts the essential amino acid phenylalanine to tyrosine. To prevent brain damage and cognitive impairment individuals with PKU must follow a lifelong, low-phenylalanine diet that is restricted in natural foods. Glycomacropeptide is uniquely suited to?the PKU diet as it contains minimal phenylalanine.
Check out Dr. Ney's article featured in the March 2012 issue of Food Technology Magazine Glycomacropeptide Provides a 'Whey' Forward for PKU
Video: 2008 PKU Nutrition Research with GMP on Wisconsin Public TV (10 min) (Scroll down to PKU Trials and click on video.)
TPN is a vital feeding technique for individuals who are unable to tolerate oral nutrition due to intestinal failure or catabolic illness. Short bowel syndrome often requires permanent TPN due to inadequate intestinal adaptation. The mechanisms underlying intestinal adaptation are poorly understood. Using a rat model for human short bowel syndrome, we have shown that coinfusion of IGF-I with TPN solution stimulates structural and functional adaptation of the residual jejunum and permits transition to enteral feeding, see Figure 1. This suggests that IGF-I or other intestinotrophic agents may improve intestinal function in humans with TPN-dependent short bowel syndrome. Current experiments are investigating the neuroendocrine pathways that mediate intestinal adaptation to resection and the intestinotrophic effects of IGF-I and GLP-2.
GLP-2 is a potent intestinal growth factor whose synthesis is nutrient dependent. It is a product of the proglucagon gene synthesized in the enteroendocrine L-cells of the distal intestine, see Figure 2. GLP-2 receptors (GLP-2R) have been localized to the brain and gastrointestinal tract with a greater concentration of GLP-2R in the proximal compared to the distal bowel.
Research Publications, Nutritional Management of PKU with GMP
Click here, to see the Research Publications, Nutritional Management of PKU with GMP.
Murali, SG, Brinkman, AS, Solverson, P, Pun,W, Pinter, JE and Ney, DM. Exogenous GLP-2 and IGF-I induce a differential intestinal response in IGF binding protein-3 and -5 double knockout mice. Am. J. Physiol. (Gastrointest Liver Physiol) 302:G794-G804, 2012.
Solverson, PM, Murali, SG, Brinkman, AS, Nelson, DW, Clayton, MK, Yen, E and Ney, DM. Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria. Am. J. Physiol. (Endoc & Metab) 302:E885-E895, 2012.
van Calcar, SC and Ney, DM. Food products made with glycomacropeptide, a low- phenylalanine whey protein, provide a new alternative to amino acid-based medical foods for nutrition management of phenylketonuria. J. Acad. Nutr. Diet. 112:1201-1210, 2012.
Brinkman, AS, Murali, SG, Hitt, S, Solverson, PM, Holst, JJ and Ney, DM. Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure. Am. J. Physiol. (Gastrointest Liver Physiol) 303:G610-G622, 2012.
Solverson, P, Murali, SG, Litscher, SJ, Blank, RD and Ney, DM. Low bone strength is a manifestation of phenylketonuria and is attenuated by a glycomacropeptide diet. PLoS ONE 7(9): e45165, 2012. doi:10.1371/journal.pone.0045165
MacLeod, EL, Clayton, MK, van Calcar, SC and Ney, D.M. Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketornuria. Mol. Genet. Metab. 100:303-308, 2010.
Koopman, MC, Chen, X, Holst, JJ, and Ney, DM. Sustained glucago-like peptide-2 infusion is required for intestinal adapation and cessation reverses increased cellularity in rats with intestinal failure. Am. J. Physiol (Gastrointest Liver Physiol) 299: G1222-G1230, 2010.
Ney, D.M., Gleason, S.T., van Calcar, S.C., MacLeod, E.L., Nelson, K.L., Etzel, M.R., Rice, G.M. and Wolff, J.A. Nutritional management of PKU with glycomarcopeptide from cheese whey. J. Inherit. Metab. Dis. 32:32-39, 2009.
van Calcar, S.C., MacLeod, E.L., Gleason. S.T., Etzel, M.R., Clayton, M.K., Wolff, J.A. and Ney, D.M. Improved nutritional management of phenylketornuria by using using a diest containing glycomarcopeptide compared with amino acids. Am J Clin Nutri 89:1068-1077, 2009.
Liu, X., Murali, S.G., Holst, J.J. and Ney, D.M. Whey protein potentiates the intestinotrophic action of glucago-like peptide-2 in parenterally-def rats. Am. J. Physiol. (Regul Integr Comp Physiol)_ 297:R1554-R1562, 2009.
Ney, D.M., Hull, A.K., van Calcar, S.C., Liu, X. and Etzel, M.R. Dietary glycomacropeptide supports growth and reduces the concentrations of phenylalanine in plasma and brain in a murine model of phenylketonuria. J. Nutr. 138:R316-R322, 2008.
Koopmann, M.C., Nelson, D.W., Murali, S.G., Liu, X., Brownfield, M.S., Holst, J.J. and Ney, D.M. Exogenous glucagon-like peptide-2 (GLP-2) augments GLP-2 receptor mRNA and maintains proglucagon mRNA levels in resected rats. J. Parenter. Enteral Nutr. 32:R254-R265, 2008.
Nelson, D.W., Sharp, J.W., Brownfield, M.S., Raybould, H.E. and Ney, D.M. Localization and activation of glucagon-like peptide-2 receptors on vagal afferents in the rat. Endocrinology 148:R1954-R1962, 2007.