EDUCATION AND TRAINING

Ph.D. (Biochemistry), University of Nottingham, Nottingham, U.K.

Fellowship, University of Washington, Division of Metabolism, Endocrinology and Nutrition

OFFICE ADDRESS

Seattle VA Puget Sound Health Care System (151)
1660 South Columbian Way
UW Mailbox 358280
Seattle, WA 98108


CURRENT RESEARCH INTERESTS
Investigations of mechanisms underlying the formation of islet amyloid from islet amyloid polypeptide (IAPP) in type 2 diabetes.  Development of in vitro models to study the role islet amyloid plays in the pathogenesis of type 2 diabetes.  The nature of heparan sulfate proteoglycans synthesized by the islet ß-cell and their role in amyloid formation.  Study of pharmacologic approaches designed to inhibit islet amyloid formation and its deleterious effect on the islet ß-cell.


REPRESENTATIVE PUBLICATIONS

Higham CE, Hull RL, Lawrie L, Shennan KIJ, Morris JF, Birch NP, Docherty K, Clark A:  Processing of synthetic pro-islet amyloid polypeptide (proIAPP) 'amylin' by recombinant prohormone convertase enzymes, PC2 and PC3, in vitro. Eur J Biochem 267:4998-5004, 2000.

Kahn SE, Andrikopoulos S, Verchere CB, Wang F, Hull RL, Vidal J:  Oophorectomy promotes islet amyloid formation in a transgenic mouse model of type 2 diabetes. Diabetologia 43:1309-1312, 2000.

Wang F, Hull RL, Vidal J, Cnop M, Kahn SE:  Islet amyloid develops diffusely throughout the pancreas before becoming severe and replacing endocrine cells. Diabetes 50:2514-3630, 2001.

Hull RL, Andrikopoulos S, Verchere CB, Vidal J, Wang F, Cnop M, Prigeon RL, Kahn SE:  Increased dietary fat promotes islet amyloid formation and ß-cell secretory dysfunction in a transgenic mouse model of islet amyloid. Diabetes 52:372-9, 2003.

Vidal J, Verchere CB, Andrikopoulos S, Wang F, Hull RL, Cnop M, Olin KL, LeBoeuf RC, O’Brien KD, Chait A, Kahn SE:  The effect of apolipoprotein E deficiency on islet amyloid deposition in human islet amyloid polypeptide transgenic mice. Diabetologia 46:71-79, 2003.

Potter-Perigo S, Hull RL, Tsoi C, Braun KR, Andrikopoulos S, Teague J, Verchere CB, Kahn SE, Wight TN:  Proteoglycans synthesized and secreted by pancreatic islet ß-cells bind amylin. Arch Biochem Biophys 413:182-190, 2003.

Andrikopoulos S, Hull RL, Verchere CB, Wang F, Wilbur SM, Marzban L, Wight TN, Kahn SE:  Extended life span is associated with insulin resistance in a transgenic mouse model of insulinoma secreting human islet amyloid polypeptide. Am J Physiol 286:E418-E424, 2004.

Hull RL, Westermark GT, Westermark P, Kahn SE:  Islet amyloid: a critical entity in the pathogenesis of type 2 diabetes. J Clin Endocrinol Metab 89:3629-3643, 2004.

Hull RL, Kodama K, Utzschneider KM, Carr DB, Prigeon RL, Kahn SE:  Dietary-fat-induced obesity in mice results in beta cell hyperplasia but not increased insulin release:  Evidence for specificity of impaired beta cell adaptation.  Diabetologia 48:1350-1358, 2005.

Hull RL, Shen ZP, Watts MR, Kodama K, Carr DB, Utzschneider KM, Zraika S, Wang F, Kahn SE:  Long-term treatment with rosiglitazone and metformin reduces the extent of, but does not prevent, islet amyloid deposition in mice expressing the gene for human islet amyloid polypeptide.  Diabetes 54:2235-2244, 2005.

Hull RL, Watts MR, Kodama K, Shen Z, Utzschneider KM, Carr DB, Vidal  J, Kahn SE:  Genetic background determines the extent of islet amyloid formation in human islet amyloid polypeptide transgenic  mice.  Am J Physiol Endocrinol Metab 289: E703-E709, 2005.

Kahn SE, Hull RL, Utzschneider KM:  Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840-846, 2006.

Zraika S, Hull RL, Udayasankar J, Utzschneider KM, Tong J, Gerchman F, Kahn SE:  Glucose- and time-dependence of islet amyloid formation in vitro. Biochem Biophys Res Commun 354:234-239, 2007.

Zraika S, Hull RL, Udayasankar J, Clark A, Utzschneider KM, Tong J, Gerchman F, Kahn SE:  Identification of the amyloid-degrading enzyme, neprilysin, in mouse islets and potential role in islet amyloidogenesis. Diabetes 56:304-310, 2007.