Progressive islet remodeling during the prediabetic stage in female SDT rats

Prediabetes represents a critical stage in the progression to type 2 diabetes, during which early alterations in pancreatic islet structure and function occur. We investigated temporal histopathological changes associated with islet remodeling in female Spontaneously Diabetic Torii (SDT) rats, a non-obese type 2 diabetes model. Focusing on structural alterations, fibrosis, altered endocrine cell organization, and pancreatic stellate cell activation. Female SDT and Sprague-Dawley (SD) rats were examined between 8 and 40 weeks of age. Blood glucose and plasma insulin levels were measured cross-sectionally in separate groups of animals from 8 to 40 weeks, and oral glucose tolerance tests (OGTTs) were performed between 16 and 24 weeks of age. Pancreatic tissues were evaluated by histopathology, immunohistochemistry, and morphometric analyses. SDT rats exhibited progressive glucose intolerance accompanied by elevated plasma insulin levels during the prediabetic stage, suggesting altered glucose homeostasis. These abnormalities were accompanied by structural alterations of islets, including architectural disruption, enlargement, and intra-islet fibrosis beginning at 18-24 weeks. Representative immunostaining suggested altered organization of insulin- and glucagon-positive endocrine cells within remodeled islets. α-SMA- and desmin-positive stromal cells were observed within fibrotic regions of SDT islets. These findings demonstrate progressive islet remodeling during the prediabetic stage in female SDT rats, characterized by structural disruption, fibrosis, and the presence of α-SMA- and desmin-positive stromal cells within fibrotic islets. These alterations may contribute to early endocrine dysfunction by disrupting the islet microenvironment and cell-cell interactions.