A New Protocol of Type 2 Diabetes Induction and Hydrocortisone Effects on Beta-Cells Signaling in Mice

Background: There are complex methods to induce type 2 diabetes as multiple low-doses streptozotocin with high fat diet administration and other combined methods which induce modest DNA damage, leading to the incomplete destruction of β cells for insulin-resistant diabetes in mice. Objective: An innovative and simple protocol was investigated to induce type 2 diabetes by only Incremental Multiple Low-Doses Streptozotocin (IMLDS) in mice. The effects of hydrocortisone injection on diabetes induction and pancreatic β-cells signaling were also surveyed. Methods: IMLDS designed protocol was conducted in 4 consecutive days by streptozotocin injections of 20, 40, 80 and 160 mg/kg BW/day and stress induced by hydrocortisone injections of 5, 10 and 20 mg/kg BW/day in mice, respectively. The glucose, insulin, glucagon-like peptide 1, RAC-beta serine/ threonine-protein kinase and dipeptidyl peptidase IV of blood were assessed by ELISA. Results: The glucose, glucagon-like peptide 1, RAC-beta serine/threonine-protein kinase levels, and food and water intake increased (p<0.01) while serum dipeptidyl peptidase IV activity decreased (p<0.01) after the administration of novel protocol. Daily injections of hydrocortisone raised blood glucose, glucagon-like peptide 1 and RAC-beta serine/threonine-protein kinase and reduced serum insulin and dipeptidyl peptidase IV activity (p<0.05). By executing this protocol, the serum insulin increased, whereas hydrocortisone injection caused reduction in the insulin (p<0.05). The hydrocortisone administration reduced glucagon-like peptide 1 in the non-induction of IMLDS conditions, but hydrocortisone enhanced glucagon-like peptide 1 after IMLDS (p<0.05). Conclusion: This new protocol may provide a practical and unique alternative chemical protocol for the induction of insulin resistance diabetes (type 2 diabetes) in mice. Stress induced by hydrocortisone also intensifies type 2 diabetes in this animal model.