Mild hyperglycemia triggered islet function recovery in streptozotocin‐induced insulin‐deficient diabetic rats

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.