Oral Administration of Lactobacillus acidophilus Expressing GLP-1 Peptide Variants with N-Terminal Extensions in Mice with Streptozotocin-Induced Hyperglycemia
- 1Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia
Abstract
Engineered bacteria are being explored as oral delivery systems for therapeutic peptides. This study examined Lactobacillus acidophilus expressing two GLP-1 peptide variants with N-terminal extensions, M-GLP-1 and M-6HIS-GLP-1, in male C57BL/6J mice with moderate streptozotocin (STZ)-induced hyperglycemia. Both purified peptides increased insulin concentrations in MIN6 conditioned medium after 24 h, but neither significantly attenuated the STZ-associated reduction in metabolic activity. Cage-level analysis showed lower average post-treatment glucose concentrations in mice receiving L. acidophilus expressing M-GLP-1 (Lacto-M-GLP-1) or M-6HIS-GLP-1 (Lacto-M-6HIS-GLP-1) than in STZ controls, but neither group differed significantly from mice receiving empty-vector L. acidophilus. The intraperitoneal glucose tolerance test showed numerically lower late-phase glucose concentrations and incremental area under the curve in both groups than in controls. Mice receiving Lacto-M-6HIS-GLP-1 showed greater body-weight change than those receiving Lacto-M-GLP-1 or empty-vector L. acidophilus. Pancreatic histology showed a lower pancreatic glucagon-positive signal area and a higher insulin-to-glucagon signal-area ratio than in STZ controls and Lacto-M-GLP-1. The findings demonstrate cellular responses to purified GLP-1 variants and metabolic changes associated with administering L. acidophilus expressing the peptides.
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BibTeX
@article{lee2026oral,
title = {{Oral Administration of Lactobacillus acidophilus Expressing GLP-1 Peptide Variants with N-Terminal Extensions in Mice with Streptozotocin-Induced Hyperglycemia}},
author = {Arthur A. Lee and Maria B. Chernysheva and Dmitry A. Kashirskikh and Evgenii S. Ruchko and Olesya O. Klychkova and Victoria A. Khotina and Tatiana V. Noskova and Vagif A. Gasanov and Ekaterina A. Vorotelyak and Andrey V. Vasiliev},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms272110003},
url = {https://www.mdpi.com/1422-0067/27/21/10003},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Oral Administration of Lactobacillus acidophilus Expressing GLP-1 Peptide Variants with N-Terminal Extensions in Mice with Streptozotocin-Induced Hyperglycemia
AU - Arthur A. Lee
AU - Maria B. Chernysheva
AU - Dmitry A. Kashirskikh
AU - Evgenii S. Ruchko
AU - Olesya O. Klychkova
AU - Victoria A. Khotina
AU - Tatiana V. Noskova
AU - Vagif A. Gasanov
AU - Ekaterina A. Vorotelyak
AU - Andrey V. Vasiliev
PY - 2026
DA - 2026/11/08
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms272110003
UR - https://www.mdpi.com/1422-0067/27/21/10003
AB - Engineered bacteria are being explored as oral delivery systems for therapeutic peptides. This study examined Lactobacillus acidophilus expressing two GLP-1 peptide variants with N-terminal extensions, M-GLP-1 and M-6HIS-GLP-1, in male C57BL/6J mice with moderate streptozotocin (STZ)-induced hyperglycemia. Both purified peptides increased insulin concentrations in MIN6 conditioned medium after 24 h, but neither significantly attenuated the STZ-associated reduction in metabolic activity. Cage-level analysis showed lower average post-treatment glucose concentrations in mice receiving L. acidophilus expressing M-GLP-1 (Lacto-M-GLP-1) or M-6HIS-GLP-1 (Lacto-M-6HIS-GLP-1) than in STZ controls, but neither group differed significantly from mice receiving empty-vector L. acidophilus. The intraperitoneal glucose tolerance test showed numerically lower late-phase glucose concentrations and incremental area under the curve in both groups than in controls. Mice receiving Lacto-M-6HIS-GLP-1 showed greater body-weight change than those receiving Lacto-M-GLP-1 or empty-vector L. acidophilus. Pancreatic histology showed a lower pancreatic glucagon-positive signal area and a higher insulin-to-glucagon signal-area ratio than in STZ controls and Lacto-M-GLP-1. The findings demonstrate cellular responses to purified GLP-1 variants and metabolic changes associated with administering L. acidophilus expressing the peptides.
SN - 1422-0067
ER -