Peptide-mediated targeting of the islets of Langerhans.
Strategies for restoring beta-cell function in diabetic patients would be greatly aided by the ability to target genes, proteins, or small molecules specifically to these cells. Furthermore, the ability to direct imaging agents specifically to beta-cells would facilitate diagnosis and monitoring of disease progression. To isolate ligands that can home to beta-cells in vivo, we have panned a random phage-displayed 20-mer peptide library on freshly isolated rat islets. We have isolated two 20-mer peptides that bind to islets ex vivo. One of these peptides preferentially homes to the islets of Langerhans in a normal rat with clear differentiation between the endocrine and exocrine cells of the pancreas. Furthermore, this peptide does not target beta-cells in a type 2 diabetes animal model, suggesting that the peptide can discriminate between glucose-stimulated insulin secretion-functional and -dysfunctional beta-cells.
Samli
Kausar N
KN
Center for Biomedical Inventions, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9185, USA.
McGuire
Michael J
MJ
Newgard
Christopher B
CB
Johnston
Stephen Albert
SA
Brown
Kathlynn C
KC
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D007340:Insulinoma; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms; D019151:Peptide Library; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019151:Peptide Library; D010455:Peptides