Hypoglycemic activity and acute toxicity of human insulin-tat mixture

• Main Authors: Aranya Manosroi, Chanutchamon Sutthiwanjampa, Worapaka Manosroi, Rolf G. Werner, Friedrich Göz, Theeraphong Tangjai, Worapong Kitdamrongtham, Jiradej Manosroi
• Format: Journal
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology; Chemistry; Materials Science; Mathematics; Physics and Astronomy
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85040939589&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/58344
• Institution: Chiang Mai University

© 2018, Chiang Mai University. All rights reserved. When orally administered in fasted alloxan-induced diabetic mice, human insulin mixed with the cell penetrating peptides, the trans-activator of transcription (Tat) gave the hypoglycemic activity, while mixed with the VP1-BC loop polioviral capsid (VP) showed no hypoglycemic activity. The insulin-Tat mixture (1:3 molar ratio) at the insulin dose of 200 IU/kg body weight showed significant different (p<0.01) in comparing to the control group with the highest percentage reduction of blood glucose level of 77.29±3.77% or 1.53 folds more than the subcutaneously injected insulin in the fasted diabetic mice after 10 hours of administration. Molecular interaction between insulin and Tat was investigated by the reflectometric interference spectroscopy (RIfS). RIfS of insulin-coated transducer chip exhibited the signal of binding or molecular interaction only with Tat, but no signal of binding with BSA and peptide7 (GAVGAVG) which were used as the controls. Acute toxicity studies revealed that insulin-Tat mixture (1:3 molar ratio) gave no toxicity and safe in mice with the LD50value of more than 2,000 mg/kg body weight. The results from this study can be used for the further development of insulin-Tat as an effective oral insulin delivery.