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.