John C. Hutton Professor Pediatrics / Cell and Developmental Biology Research Director: Barbara Davis Center for Childhood Diabetes Ph.D., New South Wales, 1972 Barbara Davis Center Room 4102 1775 N. Ursula Street P.O. Box 6515, Mail Stop B140 Aurora, CO 80045 Phone: 303-724-6837 Fax: 303-724-6839 Email: John.Hutton@ucdenver.edu

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Departmental Affiliations Department of Pediatrics Cell and Developmental Biology Trainees: Roslyn Bauer

Other Graduate Program Affiliations Biomedical Sciences Program (BSP) Medical Scientist Training Program (MSTP) Web site: Barbara Davis Center for Childhood Diabetes

Secretory granule biogenesis and exocytosis in the endocrine pancreas: role in human diabetes

My laboratory has a long-standing interest in the molecular cell biology of insulin secretion and the biochemical composition and the process of formation of the insulin storage granule of the pancreatic islet. Many insulin granule proteins are autoantigens in type 1 diabetes (insulin, IA2, phogrin, CPH) and we have focused on the molecular targets of T-cell clones isolated from a new-onset type 1 humans and the NOD mouse experimental model. The granule proteins phogrin and IA2 have been extensively studied in this context and their peptide epitopes are presently being evaluated with regard to intramolecular and intermolecular epitope spreading in the disease and as novel therapeutic agents to abrogate diabetic autoimmunity.

A mouse pancreatic islet expressing a phogrin-GFP transgene (green) within insulin (red) but not glucagon (blue) or acinar (unstained ) cells.		The C. elegans phogrin orthologue IDA-1 is expressed in a subset of worm neurones of neuroendocrine nature

Selected Publications

Achenbach P, Kelemen K, Wegmann DR, Hutton JC. Spontaneous Peripheral T-cell Responses to the IA-2beta (Phogrin) Autoantigen in Young Nonobese Diabetic Mice. J Autoimmun. 2002 Nov;19(3):111-6.

Martin CC, Oeser JK, Svitek CA, Hunter SI, Hutton JC, O'Brien RM. Identification and characterization of a human cDNA and gene encoding a ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein. J Mol Endocrinol. 2002 Oct;29(2):205-22.

Wasmeier C, Bright NA, Hutton JC. The lumenal domain of the integral membrane protein phogrin mediates targeting to secretory granules. Traffic. 2002 Sep;3(9):654-65.

Kelemen K, Wegmann DR, Hutton JC. T-cell epitope analysis on the autoantigen phogrin (IA-2beta) in the nonobese diabetic mouse. Diabetes. 2001 Aug;50(8):1729-34.

Wasmeier C, Hutton JC. Secretagogue-dependent phosphorylation of the insulin granule membrane protein phogrin is mediated by cAMP-dependent protein kinase. J Biol Chem. 2001 Aug 24;276(34):31919-28.

Latest Publications in PubMed