Induction of insulin receptor substrate-2 expression by Fc fusion to exendin-4 overexpressed in E. coli: a potential long-acting glucagon-like peptide-1 mimetic.
Exendin-4 (Ex-4), a peptide secreted from the salivary glands of the Gila monster lizard, can increase pancreatic beta-cell growth and insulin secretion by activating glucagon-like peptide-1 receptor. In this study, we expressed a fusion protein consisting of exendin-4 and the human immunoglobulin heavy chain (Ex-4/IgG-Fc) in E. coli and explored its potential therapeutic use for the treatment of insulin-resistant type 2 diabetes. Here, we show that the Ex-4/IgG-Fc fusion protein induces expression of insulin receptor substrate-2 in rat insulinoma INS-1 cells. Our findings therefore suggest that Ex-4/IgG-Fc overexpressed in E. coli could be used as a potential, long-acting glucagon-like peptide-1 mimetic.
Kim
Jae-Woo
JW
Department of Molecular Biology, Daegu University, Gyeongsan 712-714, Korea.
Kim
Kyutae
K
Ahn
Youjin
Y
Jeong
Heejeong
H
Jeong
Hyeongyong
H
Ryu
Seunghyup
S
Lee
Seungyeon
S
Lee
ChangWoo
C
Chung
Hye-Shin
HS
Jang
Sei-Heon
SH
D000818:Animals; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004926:Escherichia coli / Q000378:metabolism; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology*; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D007333:Insulin Resistance; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014688:Venoms / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D007143:Immunoglobulin Heavy Chains; D055504:Insulin Receptor Substrate Proteins; D010455:Peptides; D018027:Receptors, Glucagon; D011993:Recombinant Fusion Proteins; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide