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ARTICLE | Distillery Therapeutics

Microbial DPP-4 inhibitor for Type II diabetes

August 29, 2023 9:01 PM UTC

A daurisoline-based inhibitor of microbial DPP-4 could treat Type II diabetes by decreasing microbial DPP-4-induced degradation of host GLP-1 in the intestinal lumen, which increases active host GLP-1 plasma levels and improves glucose homeostasis.

In human stool-derived bacterial cultures, an activity screen for enzymes produced by intestinal bacteria that possess functions similar to disease-associated human proteins identified 71 microbial-host isozymes, among which statistical analyses identified microbial DPP-4 for its potential to regulate host pathophysiology. In the same cultures, DPP-4 degraded human GLP-1 peptide mimics, with five Bacteroides isolates showing the highest DPP-4 activity. ...

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