Garlic Extract Promotes Pancreatic Islet Neogenesis Through α‐to‐β‐Cell Transdifferentiation and Normalizes Glucose Homeostasis in Diabetic Rats

Scope Garlic extract (GE) has been shown to ameliorate hyperglycemia in diabetic rats (DRs) by increasing insulin production. However, the mechanism through which it exerts its effects remains unclear. Here, it investigates the molecular process and the origin of regenerating β‐cell in rats with streptozotocin (STZ)‐induced diabetes in response to GE. Methods and results In this study, quantitative RT‐PCR (qRT‐PCR), western blotting, and immunohistochemical analysis are carried out after pancreas isolation. These findings show that 1 week of GE treatment increases the expression of the endocrine progenitor cell markers Neurogenin3 (Neurog3), pancreatic and duodenal homeobox 1 (Pdx1), neurogenic differentiation factor 1 (Neurod1), paired box proteins (Pax)4, V‐maf musculoaponeurotic fibrosarcoma oncogene homolog B (Mafb), and NK homeobox factors (Nkx)6‐1 in STZ‐induced DRs. Continuation with GE treatment for 8 weeks causes the expression of the mature β‐cell markers insulin(Ins)2, urocortin3 (Ucn3), and glucose transporter 2 (Glut2) to peak. Comprehensive examination of the islet through immunohistochemical analysis reveals the presence of a heterogeneous cell population including INS+/GLUT2− and INS+/GLUT2+ β‐cell subpopulations with few bihormonal INS+/GCG+ cells after 4 weeks. By week 8, islet architecture is reestablished, and glucose‐stimulated insulin secretion was restored through the upregulation of Ucn3. Conclusion GE induces β‐cell neogenesis in DRs and restores islet architecture. The newly formed mature β‐like cells could have originated through the differentiation of endocrine progenitor cells as well as α‐ to β‐cell transdifferentiation. Garlic induces β‐cell neogenesis in STZ‐induced diabetic rats but their origin remains unclear. We identified two main sources of newly formed β‐cells through; 1) the differentiation of juvenile immature β‐cells laking GLUT2 and 2) the transdifferentiation of α‐ to β‐cells.