TFP5, a Peptide Derived from Cdk5 Activator p35, Protects Pancreatic β Cells from Glucose Toxicity

• Published in: Bulletin of experimental biology and medicine 2023-11, Vol.176 (1), p.19-25
• Main Authors: Liu, S.-Y., Cao, S.-L., Luo, H.-Y., Bao, L., E, J., Li, B., Lan, X.-M., Zhang, G.-Q., Bao, X., Zheng, Y.-L.
• Format: Article
• Language: English
• Subjects: Amino acids; Apoptosis; Beta cells; Biomedical and Life Sciences; Biomedicine; C-Terminus; Cell Biology; Cyclin-dependent kinase 5; Cyclin-dependent kinases; Diabetes; Diabetes mellitus (non-insulin dependent); Hyperactivity; Inflammation; Insulin secretion; Internal Medicine; Kinases; Laboratory Medicine; N-Terminus; p35 Protein; Pancreas; Pathology; Peptides; Tat protein; Toxicity; Transforming growth factor-b1
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-023-05959-z

We studied the effect of TFP5 on MIN6 cells (cultured mouse islet β cells) treated with different concentrations of glucose (5 or 25 mM). The results were verified in C57BL/6J mice (control; n =12) and db/db mice with type 2 diabetes mellitus ( n =12). To synthesize TFP5, peptide p5 (a derivative of p35 protein, activator of cyclin-dependent kinase 5, Cdk5) was conjugated with a FITC tag at the N-terminus and an 11-amino acid TAT protein transduction domain at the C-terminus. TFP5 was employed to inhibit Cdk5 activity and then to evaluate its efficiency in treating experimental type 2 diabetes mellitus. TFP5 effectively inhibited the pathological hyperactivity of Cdk5, enhanced insulin secretion, and protected pancreatic β cells from apoptosis in vitr o and in vivo . In addition, TFP5 inhibited inflammation in pancreatic islets by reducing the expression of inflammatory cytokines TGF-β1, TNFα, and IL-1β. These novel data indicates that TFP5 is a promising candidate for treatment of type 2 diabetes mellitus.