A new orally available glucagon-like peptide-1 receptor agonist, biotinylated exendin-4, displays improved hypoglycemic effects in db/db mice

Journal of Controlled Release

Volumn 133, Issue 3, 2009, Pages 172-177

  Jin, Cheng Hao ^a,c   Chae, Su Young ^a,c   Son, Sohee ^a,c   Kim, Tae Hyung ^a,c   Um, Key An ^a,c   Youn, Yu Seok ^b,c   Lee, Seulki ^b,c   Lee, Kang Choon ^a,c  

^a Sungkyunkwan University   (South Korea)

^b Pusan National University   (South Korea)

^c Korea Institute of Science and Technology   (South Korea)

Author keywords

Absorption; Biotinylation; Exendin 4; Oral hypoglycemic efficacy; Stability; Type 2 diabetes

Indexed keywords

ABSORPTION; AMINES; BINDING ENERGY; COENZYMES; DRUG PRODUCTS; SUGAR (SUCROSE);

BIOTINYLATION; EXENDIN-4; ORAL HYPOGLYCEMIC EFFICACY; STABILITY; TYPE 2 DIABETES;

INDUSTRIAL LABORATORIES;

ANTIDIABETIC AGENT; EXENDIN 4; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCOSE; INSULIN; LYSINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOTINYLATION; C57BL MOUSE; CELL ISOLATION; CONTROLLED STUDY; DRUG ABSORPTION; DRUG ACTIVITY; DRUG EFFECT; DRUG RECEPTOR BINDING; DRUG STABILITY; ENZYME STABILITY; GLUCOSE BLOOD LEVEL; IN VITRO STUDY; INSULIN RELEASE; INSULINOMA; INTESTINE ABSORPTION; MALE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; RAT; RECEPTOR AFFINITY; SPRAGUE DAWLEY RAT; THERAPY EFFECT; TREATMENT OUTCOME; TREATMENT RESPONSE;

ADMINISTRATION, ORAL; ANIMALS; AREA UNDER CURVE; BIOTIN; BIOTINYLATION; BLOOD GLUCOSE; BODY FLUIDS; DRUG CARRIERS; GLUCAGON-LIKE PEPTIDE 1; GLUCOSE; GLUCOSE TOLERANCE TEST; HYPOGLYCEMIC AGENTS; INSULIN; ISLETS OF LANGERHANS; MALE; MICE; MICE, INBRED C57BL; MICE, MUTANT STRAINS; MICE, OBESE; PEPTIDES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, GLUCAGON; RECEPTORS, LEPTIN; SUCCINIMIDES; TRYPSIN; VENOMS;

EID: 58549086777     PISSN: 01683659     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jconrel.2008.09.091     Document Type: Article

References (24)

1. Eng J., Kleinman W.A., Singh L., Singh G., and Raufman J.P. Isolation and characterization of exendin-4, an exendin-3 analogue from Heloderma suspectum venom. J. Biol. Chem. 267 (1992) 7402-7405
2. Gallwitz B. New therapeutic strategies for the treatment of type 2 diabetes mellitus based on incretins. Rev. Diabet. Stud. 2 (2005) 61-69
3. Todd J.F., and Bloom S.R. Incretins and other peptides in the treatment of diabetes. Diabet. Med. 24 (2007) 223-232
4. Drucker D.J., and Nauck M.A. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368 (2006) 1696-1705
5. Parkes D.G., Pittner R., Jodka C., Smith P., and Young A. Insulinotropic actions of exendin-4 and glucagon-like peptide-1 in vivo and in vitro. Metabolism 50 (2001) 583-589
6. Young A.A., Gedulin B.R., Bhavsar S., Bodkin N., Jodka C., Hansen B., and Denaro M. Glucose-lowering and insulin-sensitizing actions of exendin-4: studies in obese diabetic (ob/ob, db/db) mice, diabetic fatty Zucker rats, and diabetic rhesus monkeys (Macaca mulatta). Diabetes 48 (1999) 1026-1034
7. Egan J.M., Clocquet A.R., and Elahi D. The insulinotropic effect of acute exendin-4 administered to humans: comparison of nondiabetic state to type 2 diabetes. J. Clin. Endocrinol. Metab. 87 (2002) 1282-1290
8. Kolterman O.G., Buse B., Fineman M.S., Gaines E., Heintz S., Bicsak T.A., Taylor K., Kim D., Aispoma M., Wang Y., and Baron A.D. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J. Clin. Endocrinol. Metab. 88 (2003) 3082-3089
9. Nielsen L.L., Young A.A., and Parkes D.G. Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Regul. Pept. 117 (2004) 77-88
10. Szayna M., Doyle M.E., Betkey J.A., Holloway H.W., Spencer R.G., Greig N.H., and Egan J.M. Exendin-4 decelerates food intake, weight gain, and fat deposition in Zucker rats. Endocrinology 141 (2000) 1936-1941
11. Mansoor S., Youn Y.S., and Lee K.C. Oral delivery of mono-PEGylated sCT (Lys18) in rats: regional difference in stability and hypocalcemic effect. Pharm. Dev. Technol. 10 (2005) 389-396
12. Youn Y.S., Chae S.Y., Lee S., Kwon M.J., Shin H.J., and Lee K.C. Improved peroral delivery of glucagon-like peptide-1 by site-specific biotin modification: design, preparation, and biological evaluation. Eur. J. Pharm. Biopharm. 68 (2008) 667-675
13. Chae S.Y., Jin C.H., Shin H.J., Youn Y.S., Lee S., and Lee K.C. Preparation, characterization, and application of biotinylated and biotin-PEGylated glucagon-like peptide-1 analogues for enhanced oral delivery. Bioconjug. Chem. 19 (2008) 334-341
14. Balamurugan K., Ortiz A., and Said H.M. Biotin uptake by human intestinal and liver epithelial cells: role of the SMVT system. Am. J. Physiol., Gastrointest. Liver Physiol. 285 (2003) G73-77
15. Ramanathan S., Pooyan S., Stein S., Prasad P.D., Wang J., Leibowitz M.J., Ganapathy V., and Sinko P.J. Targeting the sodium-dependent multivitamin transporter (SMVT) for improving the oral absorption properties of a retro-inverso Tat nonapeptide. Pharm. Res. 18 (2001) 950-956
16. Lee S.H., Lee S., Youn Y.S., Na D.H., Chae S.Y., Byun Y., and Lee K.C. Synthesis, characterization, and pharmacokinetic studies of PEGylated glucagon-like peptide-1. Bioconjug. Chem. 16 (2005) 377-382
17. Youn Y.S., Chae S.Y., Lee S., Jeon J.E., Shin H.G., and Lee K.C. Evaluation of therapeutic potentials of site-specific PEGylated glucagon-like peptide-1 isomers as a type 2 anti-diabetic treatment: insulinotropic activity, glucose-stabilizing capability, and proteolytic stability. Biochem. Pharmacol. 73 (2007) 84-93
18. Hargrove D.M., Kendall E.S., Reynolds J.M., Lwin A.N., Herich J.P., Smith P.A., Gedulin B.R., Flanagan S.D., Jodka C.M., Hoyt J.A., McCowen K.M., Parkes D.G., and Anderson C.M. Biological activity of AC3174, a peptide analog of exendin-4. Regul. Pept. 141 (2007) 113-119
19. Lee S., Youn Y.S., Lee S.H., Byun Y., and Lee K.C. PEGylated glucagon-like peptide-1 displays preserved effects on insulin release in isolated pancreatic islets and improved biological activity in db/db mice. Diabetologia 49 (2006) 1608-1611
20. Hamman J.H., Enslin G.M., and Kotze A.F. Oral delivery of peptide drugs: barriers and developments. BioDrugs 19 (2005) 165-177
21. Fix J.A. Oral controlled release technology for peptides: status and future prospects. Pharm. Res. 13 (1996) 1760-1764
22. Muranishi S. Delivery system design for improvement of intestinal absorption of peptide drugs. Yakugaku Zasshi 117 (1997) 394-414
23. Mahato R.I., Narang A.S., Thoma L., and Miller D.D. Emerging trends in oral delivery of peptide and protein drugs. Crit. Rev. Ther. Drug Carrier Syst. 20 (2003) 153-214
24. Bernkop-Schnürch A. The use of inhibitory agents to overcome the enzymatic barrier to perorally administered therapeutic peptides and proteins. J. Control. Release 52 (1998) 1-16