Abstract
This commentary discusses our recent findings that, contrary to the β-cell rest hypothesis, early short-term insulin administration in a mouse model of marginal β-cell deficiency paradoxically worsened glycemic control and induced adverse α-cell-mediated islet remodeling. Early insulin intervention is hypothesized to preserve β-cell function; however, its utility in marginal β-cell deficiency is not well-established. Our recent study investigated the effects of early insulin administration versus syngeneic islet transplantation in a 50% pancreatectomy mouse model, which mimics a state of marginal β-cell deficiency while maintaining normoglycemia. Contrary to our expectation, short-term exogenous insulin treatment resulted in a paradoxical worsening of glycemic control and induced adverse islet remodeling. Histological analyses revealed this was driven by a significant expansion of α-cells, attributable to both increased proliferation and neogenesis. In contrast, syngeneic islet transplantation achieved superior glycemic control and preserved near-normal islet architecture. These findings suggest that prophylactic insulin use in early dysglycemia may not confer a protective effect and could inadvertently accelerate islet dysfunction. Rather, islet transplantation remains a more effective strategy for maintaining metabolic stability and islet structure in insulin-deficient states. This work calls for caution in the early initiation of insulin treatment in diabetic patients and highlights the need for further investigation into the effects of exogenous insulin on α-cell biology.
Keywords
50% Pancreatectomy, Islet transplantation, Early insulin treatment, Islet morphology