A potent, non-toxic insulin-releasing peptide isolated from an extract of the skin of the Asian frog, Hylarana guntheri (Anura:Ranidae).
Peptides in extract of the skin of the Asian frog Hylarana guntheri Boulenger,1882 were purified by reversed-phase HPLC and individual components analysed for their ability to release insulin from the rat BRIN-BD11 clonal beta cell line. The most potent peptide identified in the extract belonged to the brevinin-2 family (brevinin-2GUb; GVIIDTLKGAAKTVAAELLRKAHCKLTNSC). Other peptides with weaker insulin-releasing activity belonged to the brevinin-1 (2 peptides), brevinin-2 (2 peptides) and temporin (3 peptides) families. Only the brevinin-1 peptides showed cytolytic activity against the BRIN-BD11 cells, as demonstrated by an increased rate of release of the cytosolic enzyme, lactate dehydrogenase. A synthetic replicate of brevinin-2GUb produced a significant stimulation of insulin release (139% of basal rate; P<0.05) at a concentration of 100 nM with a maximum response of 373% of basal rate at a concentration of 3 microM) by a mechanism that did not involve mobilization of intracellular calcium. Brevinin-2GUb also inhibited the growth of microorganisms (MIC against Escherichia coli=32 microM, Staphylococcus aureus=64 microM, and Candida albicans=64 microM) but had only weak hemolytic activity against human erythrocytes (LC(50)=700 microM). Administration of brevinin-2GUb (75 nmol/kg body weight) into mice significantly (P<0.05) improved glucose tolerance following a intraperitoneal injection of glucose, thereby demonstrating that the peptide shows potential for development into a therapeutically valuable agent for the treatment of Type 2 diabetes.
Conlon
J Michael
JM
Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, 17666 Al-Ain, United Arab Emirates. jmc2016@qatar-med.cornell.edu.
Power
Gavin J
GJ
Abdel-Wahab
Yasser H A
YH
Flatt
Peter R
PR
Jiansheng
Hu
H
Coquet
Laurent
L
Leprince
Jérôme
J
Jouenne
Thierry
T
Vaudry
Hubert
H
D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011898:Ranidae / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012867:Skin / Q000737:chemistry
D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; D001786:Blood Glucose; D007328:Insulin