title: Mild hyperglycemia triggered islet function recovery in streptozotocin-induced insulin-deficient diabetic rats.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.|Department of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Endocrinology, Chinese PLA 309 Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.affiliation: Chinese PLA General Hospital, Beijing, China.
authors.forename: Weizheng
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Hao
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.|Department of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Zongyan
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Department of Molecular Biology, Institute of Basic Medicine, School of Life Science, Chinese PLA General Hospital, Beijing, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D050416:Glucagon-Secreting Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin
keywords: Islet function recovery; Mild hyperglycemia; β-Cell proliferation