Leucine-glycine and carnosine dipeptides prevent diabetes induced by multiple low-doses of streptozotocin in an experimental model of adult mice.

AIMS/

introductionPeptides are considered to be quasi-hormones and effective molecules for regulation of the cells function and prevention of metabolic disorders. Di- and tripeptides gastrointestinal absorption ability have been proposed to prevent diabetes progression. MATERIALS AND

methodsSmall peptides with different sequences of specific amino acids were synthesized based on a solid phase peptide synthesis protocol, and carnosine (A) and glutathione were examined for the prevention of diabetes induced by multiple low-doses of streptozotocin in mice.

resultsThe peptides A, Leu-Gly (D) and Pro-Pro showed preventive effects on blood glucose elevation and impairment of the signaling and performance of β-cells. The β-cell function assessed by immunofluorescence and blood glucose level in mice exposed to diabetes treated by the peptides A and D was similar to the normal mice. The peptide D prevented bodyweight loss caused by diabetes induction. The use of D and A peptides dramatically prevented the incidence of disruption in β-cells signaling by maintaining the natural balance of intracellular Akt-2 and cyclic adenosine monophosphate.

conclusionsThe results proved that peptide D (Leu-Gly), named Hannaneh, inhibits the bodyweight loss caused by diabetes induction. The Hannaneh and carnosine dipeptides, with preservation of normal β-cell signaling and anti dipeptidyl peptidase-4 activity, prevented blood glucose increases in mice at risk of diabetes. These dipeptides might be regarded as the pharmaceutical agents for the prevention of diabetes.