Maria B. Chernysheva

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.

Pancreatic regeneration is a complex process observed in both normal and pathological conditions. The aim of this review is to provide a comprehensive understanding of the emergence of a functionally active population of insulin-secreting β-cells in the adult pancreas. The renewal of β-cells is governed by a multifaceted interaction between cellular sources of genetic and epigenetic factors. Understanding the development and heterogeneity of β-cell populations is crucial for functional β-cell regeneration. The functional mass of pancreatic β-cells increases in situations such as pregnancy and obesity. However, the specific markers of mature β-cell populations and postnatal pancreatic progenitors capable of increasing self-reproduction in these conditions remain to be elucidated. The capacity to regenerate the β-cell population through various pathways, including the proliferation of pre-existing β-cells, β-cell neogenesis, differentiation of β-cells from a population of progenitor cells, and transdifferentiation of non-β-cells into β-cells, reveals crucial molecular mechanisms for identifying cellular sources and inducers of functional cell renewal. This provides an opportunity to identify specific cellular sources and mechanisms of regeneration, which could have clinical applications in treating various pathologies, including in vitro cell-based technologies, and deepen our understanding of regeneration in different physiological conditions.

This paper presents the results of a study of developmental dynamics of pathological changes in the liver tissue of different aged mice with induced fibrosis, and also shows the role of melatonin as hepatoprotector. It was demonstrated that the toxic damage causes more severe pathological changes in the structure of liver tissue of old animals than of younger ones. The use of melatonin demonstrates a tendency to reduce the degree of liver fibrotization in young animals with induced fibrosis.