Development for Probiotics Based Insulin Delivery System

Area of Science:

• Biotechnology
• Endocrinology
• Microbiology

Background:

• Probiotics demonstrate therapeutic potential for diabetes mellitus (DM).
• Developing recombinant insulins with enhanced properties and oral delivery methods is crucial for DM management.
• Current insulin therapies face challenges including administration and potential side effects.

Purpose of the Study:

• To evaluate the impact of a flexible linker peptide on the characteristics of single-chain insulin (insulin-CBT1).
• To assess the biological anti-diabetic properties of insulin-CBT1 compared to commercial insulin.
• To develop and validate a novel oral delivery system for insulin-CBT1 using Pediococcus pentosaceus (PP).

Main Methods:

• Characterization of insulin-CBT1's physical and structural properties, focusing on the effect of a flexible linker peptide.
• In vitro assessment of insulin-CBT1's effects on MIN6 cell proliferation and 3T3-L1 cell differentiation and glucose uptake.
• Development of an oral delivery system by engineering Pediococcus pentosaceus (PP) to secrete insulin-CBT1.

Main Results:

• The flexible linker peptide significantly increased the alpha-helix content of insulin-CBT1 (19.3% to 25.6%).
• Insulin-CBT1 demonstrated superior MIN6 cell proliferation (1.75-fold increase) compared to commercial insulin, with lower 3T3-L1 differentiation and glucose uptake rates.
• The Pediococcus pentosaceus-based delivery system successfully secreted insulin-CBT1 into the culture medium.

Conclusions:

• The engineered insulin-CBT1 possesses favorable structural and biological properties for diabetes treatment.
• A novel probiotic-based oral delivery system for insulin-CBT1 was successfully developed, offering a potential alternative to traditional insulin administration.
• This research opens new therapeutic avenues for managing diabetes mellitus through advanced biotechnology and probiotics.