Table 5.
Representative antidiabetic peptides (ADPs) isolated from various species of amphibians.
| Peptides | Species (Common Name) |
Assay(s) | Amino Acid Sequence | Reference |
|---|---|---|---|---|
| Alyteserin-2a |
Alytes obstetricans (Midwife toad) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (TC: 30 nM, Basal release of insulin at 3 μM: 296 ± 26%). In vivo studies: ns. | ILGKLLSTAAGLLSNL | [100] |
| Amolopin |
Amolops loloensis (Loloku sucker frog) |
Insulin release (in vitro): INS-1 (significantly increased insulin release from 40 to 50 mLU/L at 12.5–50 μg/mL). | FLPIVGKSLSGLSGKL | [98] |
| Bombesin (protein fractions) |
Bombina variegate (Yellow-bellied toad) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (insulin secretion: 1.5–3.5 ng/106 cells/20 min). | EQRLGHQWAVGHLM | [98] |
| Bombesin-related peptide |
Bombina variegate (Yellow-bellied toad) |
– | EDSFGNQWARGHFM | [98] |
| Brevinin-1CBb |
Lithobates septentrionalis (Mink frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (1.0–3.0 ng/106 cells/20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (101.5–144.3% of control). | FLPFIARLAAKVFPSIICSVTKKC | [98,101] |
| Brevinin-1Pa |
Rana pipiens (Northern leopard frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells. | FLPIIAGVAAKVFPKIFCAISKKC | [98] |
| Brevinin-1E |
Rana esculenta (Green frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells. | FLPAIFRMAAKVVPTIICSITKKC | [98] |
| Brevinin-2GUb |
Hylarana guentheri (Günther’s frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (0.7–1.8 ng/106 cells/20 min). | GVIIDTLKGAAKTVAAELLRKAHCKLTNSC | [98,102] |
| Brevinin-2EC |
Pelophylax esculentus (European black-spotted frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells. | GILLDKLKNFAKTAGKGVLQSLLNTASCKLSGQC | [98] |
| Brevinin-2-related peptide (B2RP) |
Lithobates septentrionalis (Mink frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells. | GIWDTIKSMGKVFAGKILQNL | [98] |
|
Lithobates septentrionalis (Mink frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells. | GMASKAGSVLGKVAKVALKAAL | ||
| Caerulein-B1 |
Xenopus borealis (Marsabit clawed frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (1.4 ± 0.1 ng/106 cells/20 min, stimulated rate 1.8 ± 0.0 ng/106 cells/20 min). | EQDY(SO3)GTGWMDF | [98,103] |
| CPF-AM1 |
Xenopus amieti (Volcano clawed frog) |
GLP-1-releasing activity by GLUTag cells (in vitro): 3.2-fold greater than basal rate at 3 μM concentration). | GLGSVL GKALKIGANLL-NH2 | [14] |
| Dermaseptin B4 |
Phyllomedusa trinitatis (Trinidadian monkey frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells. | ALWKDILKNVGKAAGKAVLNTVTDMVNQ | [98] |
| Dermaseptin-LI1 |
Agalychnis litodryas (Red-eyed treefrog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells. | AVWKDFLKNIGKAAGKAVLNSVTDMVNE | [98] |
| Esculentin-1 |
Rana esculenta (Green frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (3.0 ± 0.3 ng/106 cells/20 min). | GIFSKLGRKKIKNLLISGLKNVGKEVGMDVVRTGIDIAGCKIKGEC | [98,104] |
| Esculentin-1b |
Rana esculenta (Green frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (2.9 ± 0.2 ng/106 cells/20 min). | GIFSKLAGKKLKNLLISGLKNVGKEVGMDVVRTGIDIAGCKIKGEC | [98,104] |
| Esculentin-2Cha |
Lithobates chiricahuensis (Chiricahua leopard frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (TC: 0.3 nM). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (102.7 ± 1.1% of control). Insulin-releasing activity in high fat fed mice (in vivo): Plasma insulin (AUC: 165.0 ± 16. 9 ng/mL/min). |
GFSSIFRGVAKFASKGLGKDLAKLGVDLVACKISKQC | [105] |
| GM-14 |
Bombina variegate (Yellow-bellied toad) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells. | GKPFYPPPIYPEDM | [98] |
| GPPGPA |
Andrias davidianus (Chinese giant salamander) |
α-glucosidase inhibitory activity (in vitro): IC50 (0.3 ± 0.1 mg/mL). | Unknown. | [99] |
| Hymenochirin-1B |
Hymenochirus boettgeri (Zaire dwarf clawed frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (TC: 1.0 nM, Insulin release at 1 μM: 13.4 ± 0.1% of total insulin content, Basal release of insulin at 1 nM: 304.4 ± 19.4%). | IKLSPETKDNLKKVLKGAIKGAIAVAKMV | [98,106] |
| IN-21 |
Bombina variegate (Yellow-bellied toad) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells. | IYNAICPCKHCNKCKPGLLAN | [98] |
| Magainin-AM1 |
Xenopus amieti (Volcano clawed frog) |
GLP-1-releasing activity (in vitro): GLUTag cells (1.1–2.0 pg/106 cells/h). | GIKEFAHSLGKFG KAFVGGILNQ | [14] |
| Magainin-AM2 |
Xenopus amieti (Volcano clawed frog) |
GLP-1-releasing activity (in vitro): GLUTag cells (1.1–2.7 pg/106 cells/h). | GVSKILHSAGKFGKAFLGEIMKS | [14] |
| Ocellatin-L2 |
Leptodactylus laticeps (Santa Fe white-lipped frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (181% of basal rate at 3 μM). | GVVDILKGAAKDLAGHLATKVMDKL | [98,107] |
| Palustrin-1c |
Lithobates palustris (Pickerel frog) |
– | ALSILRGLEKLAKMGIALTNCKATKKC | [98] |
| Palustrin-2CBa |
Rana catesbeiana (American bullfrog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (1.1–2.4 ng/106 cells/20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (100.3–104.4% of control). | GFLDIIKDTGKEFAVKILNNLKCKLAGGCPP | [98,101] |
| PGLa-AM1 |
Xenopus amieti (Volcano clawed frog) |
GLP-1-releasing activity (in vitro): GLUTag cells (1.1–2.6 pg/106 cells/h). | GMASKAGSVLGKVAKVALKAAL-NH2 | [14] |
| Phylloseptin-L2 |
Hylomantis lemur (Lemur tree frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (2.2 ± 0.2 ng/106 cells/20 min). Insulin-releasing activity in mice (in vivo): Plasma insulin (AUC: 59 ng/mL/min). |
FLSLIPHVISALSSL | [98,108] |
| Plasticin-L1 |
Leptodactylus laticeps (Santa Fe white-lipped frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (1.0–1.7 ng/106 cells/20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (101.1–113.7% of basal release). | GLVNGLLSSVLGGGQGGGGLLGGIL | [98,107] |
| Pseudhymenochirin-1Pb |
Pseudhymenochirus merlini (Merlin’s dwarf gray frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (1.0–5.0 ng/106 cells/20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (460% of control at 3 μM). | GIFPIFAKLLGKVIKVASSLISKGRTE | [98,109] |
| Pseudhymenochirin-2Pa |
Pseudhymenochirus merlini (Merlin’s dwarf gray frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (1.0–7.0 ng/106 cells/20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (<1500% of control at 3 μM). | IKIPSFFRNILKKVGKEAVSLIAGALKQS | [98,109] |
| Pseudin-2 |
Pseudis paradoxa (Shrinking frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (1.0–2.0 ng/106 cells/20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (100–150% of control). | GLNALKKVFQGIHEAIKLINNHVQ | [98,110] |
| Ranatuerin-1CBa |
Rana catesbeiana (American bullfrog) |
– | SMLSVLKNLGKVGLGFVACKVNKQC | [98] |
| Ranatuerin-2CBc |
Rana catesbeiana (American bullfrog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (1.0–2.8 ng/106 cells × 20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (98.8–103.7% of control). | GFLDIIKNLGKTFAGHMLDKIKCTIGTCPPSP | [98,101] |
| Ranatuerin-2CBd |
Rana catesbeiana (American bullfrog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (1.2–2.5 ng/106 cells × 20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (99.2–103.8% of control). | GFLDIIKNLGKTFAGHMLDKIRCTIGTCPPSP | [98,101] |
| RK-13 |
Agalychnis calcarifer (Costa Rican flying tree frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (0.8–1.5 ng/106 cells × 20 min). | RRKPLFPLIPRPK | [98,111] |
| Temporin-CBa |
Rana catesbeiana (American bullfrog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (0.9–2.1 ng/106 cells × 20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (101.2–104.8 % of control). | FLPIASLLGKYL | [98,101] |
| Temporin-CBf |
Rana catesbeiana (American bullfrog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (1.0–2.4 ng/106 cells × 20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (101.2–103.9% of control). | FLPIASMLGKYL | [98,101] |
| Temporin-DRa |
Rana draytonii (California red-legged frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (0.6–0.9 ng/106 cells × 20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (3.5–6.4% of total cell content). | HFLGTLVNLAKKIL | [98,112] |
| Temporin-DRb |
Rana draytonii (California red-legged frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (0.6–1.5 ng/106 cells × 20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (3.7–5.7% of total cell content). | NFLGTLVNLAKKIL | [98,112] |
| Temporin-Oe |
Rana ornativentris (Montane brown frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (0.7–2.3 ng/106 cells × 20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (6.2–9.2% of total cell content). | ILPLLGNLLNGLL | [98,112] |
| Temporin-TGb |
Rana tagoi (Tago’s brown frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (0.6–1.8 ng/106 cells × 20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (4.0–5.6% of total cell content). | AVDLAKIANKVLSSLF | [98,112] |
| Temporin-Va |
Lithobates virgatipes (Carpenter frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (0.8–1.5 ng/(106 cells × 20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (7.4–13.6% of total cell content). | FLSSIGKLIGNLL | [98,112] |
| Temporin-Vb |
Lithobates virgatipes (Carpenter frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (0.8–1.7 ng/106 cells × 20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (7.4–9.8% of total cell content). | FLSIIAKVLGSLF | [98,112] |
| Temporin-Vc |
Lithobates virgatipes (Carpenter frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (0.8–2.6 ng/106 cells × 20 min). LDH-releasing activity (in vitro): BRIN-BD11 clonal β-cells (7.4–10.9% of total cell content). | FLPLVTMLLGKLF | [98,112] |
| Tigerinin-1R |
Rana tigerina (Asian bullfrog) |
GLUTag cell culture (in vitro), glucose homeostasis and beta cell function in mice with diet-induced obesity-diabetes (in vivo). | RVCSAIPLPICH | [14,24] |
| Xenopsin |
Xenopus amieti (Volcano clawed frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (1.5–2.1 ng/106 cells/20 min). | EGKRPWIL | [98,103] |
| Xenopsin-AM2 |
Xenopus amieti (Volcano clawed frog) |
Insulin-releasing activity (in vitro): BRIN-BD11 clonal β-cells (1.0–2.0 ng/106 cells/20 min). | EGRRPWIL | [98,103] |
AUC: area under curve; TC: threshold concentration (minimum concentration of peptide producing a significant (p < 0.05) increase in the rate of insulin release); Basal release: the rate of insulin release in the absence of peptide and is set at 100%; IC50: half maximal inhibitory concentration; GLP-1: glucagon-like peptide-1; ns.: not significant; –: not specified.