Abstract
AIMS/INTRODUCTION: Moderate elevation of glucose level has been shown to effectively promote β-cell replication in various models in vitro and in normal rodents. Here, we aimed to test the effect of moderately elevated glucose on β-cell mass expansion and islet function recovery in diabetic animal models. MATERIALS AND METHODS: A single high dose of streptozotocin was given to induce insulin-deficient diabetes in adult male Sprague-Dawley rats. Then, 48 h after streptozotocin injection, newly diabetic rats were randomly divided into three groups: (i) no treatment to maintain hyperglycemia; (ii) daily exogenous long-acting human insulin analog injection that maintained mild hyperglycemia (15 mmol/L < blood glucose < 18 mmol/L); (iii) daily exogenous long-acting human insulin analog injection to restore normoglycemia (blood glucose <8 mmol/L) as a control. Islet function, β-cell regeneration and β-cell replication were monitored during the entire analysis period. RESULTS: A single high dose of streptozotocin induced massive loss of β-cells, resulting in irreversible hyperglycemia. Mild hyperglycemia markedly promoted β-cell proliferation, leading to robust β-cell regeneration. Importantly, rats that maintained mild hyperglycemia showed nearly normal glucose-stimulated insulin secretion, glucose disposal and random blood glucose levels, suggesting almost full restoration of the islet function. Normalization of blood glucose levels profoundly blunted β-cell replication, regeneration and islet function recovery observed in mild hyperglycemia. CONCLUSIONS: Our research provides a feasible approach to stimulate in situ β-cell regeneration in diabetic rats, offering new perspectives for diabetes therapy.