Islet Transplantation Provides Superior Glycemic Control and Maintenance of Better Islet Architecture Compared to Early Insulin Treatment in 50% Pancreatectomized Mice

Abstract

Early insulin intervention is speculated to promote β-cell rest, potentially preserving and regenerating residual β-cells in β-cell-deficient environments, such as recent-onset type 1 diabetes. However, exogenous insulin supplementation is supposed not to be enough to fulfill these beneficial outcomes. To investigate this, we employed a 50% partial pancreatectomy (Px) in mice as a model for β-cell deficiency. Four experimental groups are included: 1. a sham group that underwent 50% Px (sham group), 2. control group that underwent 50% Px with saline injection for 7 days (Px group), 3. insulin group that administered insulin injection for 7 days post-Px (PX+INS group) and 4. islet transplantation group that islet transplantation after 50% Px. (PX+IT group). Intraperitoneal glucose tolerance tests (IPGTTs) were performed at 3- and 7-days postinsulin treatment or IT, and glycemic control was assessed by calculating the area under the curve (AUC) of blood glucose concentrations. Histomorphometric analysis was used to evaluate islet distribution, islet morphology and the composition of β- and α-cells. The results showed significantly improved glucose tolerance at 3- and 7- days in the islet-transplantation group compared to the insulin-treated group. Islet proportions in the pancreas were similar across groups; however, the insulin-treated group exhibited a significant increase in α-cell numbers, with their distribution extending both to the periphery and inner core of the islets. Our findings demonstrate that islet transplantation is superior to insulin treatment for glycemic control following 50% pancreatectomy in mice. Short-term insulin treatment was associated with α-cell expansion and worsened glycemic outcomes. These results suggest that islet transplantation is more effective in β-cell-deficient conditions, and caution is warranted when implementing early preventive insulin interventions.