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Human GLP‐1α and GIPα: novel, long‐acting nanomedicines for type II diabetes mellitus
Author(s) -
Rubinstein Israel,
Lim Sok Bee,
Jeon Eunjung,
Önyüksel Hayat
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a434-c
Subject(s) - incretin , glucagon like peptide 1 , in vivo , chemistry , circular dichroism , type 2 diabetes mellitus , saline , ethylene glycol , gastric inhibitory polypeptide , exenatide , medicine , endocrinology , diabetes mellitus , biochemistry , type 2 diabetes , hormone , glucagon , biology , organic chemistry , microbiology and biotechnology
Objectives: Glucagon‐like peptide‐1 (GLP‐1) and gastric inhibitory peptide (GIP), two incretin hormones, are developed to treat type II diabetes mellitus (DM). However, their clinical application is hampered by a short half‐life in vivo. Accordingly, we developed novel, long‐acting nanoformulations of both peptides consisting of self‐associated GLP‐1 and GIP with biocompatible and biodegradable sterically stabilized phospholipid nanomicelles (SSM). Methods: SSM composed of poly(ethylene glycol‐2000)‐grafted distearoylphosphatidylethanolamine (size, 15 nm) were prepared as previously described in our laboratory 1 . Human GLP‐1 or GIP was added to nanomicelles dispersed in saline, incubated for 2 h at room temperature and analyzed by circular dichroism and fluorescence spectroscopy. Results and discussion: α‐Helicity of GLP‐1 and GIP increased significantly in the presence of SSM (33±7%&29±3% respectively; n=3; mean±SD) compared to that in saline (11±1%&12±2% respectively; n=3; p<0.05). This conformation protects the peptides from hydrolysis and inactivation and is optimal for ligand‐receptor interactions. Self‐association of GLP‐1 and GIP with SSM was confirmed by a significant increase in fluorescence intensity compared to that of the peptides in saline (n=3; p<0.05). Conclusions: Human GLP‐1 and GIP interact avidly with SSM leading to increased α‐helicity of the peptides. We propose that human GLP‐1α and GIPα should be tested as novel, long‐acting nanomedicines for type II DM. Acknowledgements: Supported, in part, by NIH grants R01 AG024026 and R01 HL72323 and VA merit Review