Protective effects of di- and tri-peptides containing proline, glycine, and leucine on liver enzymology and histopathology of diabetic mice.

CONTEXT: Small peptides as multifunctional biomolecules can prevent the metabolic disorders such as diabetes. OBJECTIVE: The purpose of this study was to investigate the effects of small peptides on the enzymes and histopathology of the liver in mice exposed to diabetes. METHODS: Di- and tri-peptides containing proline, glycine, and leucine were produced by solid phase peptide synthesis (SPPS) protocol. The effects of produced peptides as well as carnosine (Ala-His) and glutathione (Glu-Cys-Gly) were evaluated on hepatic enzymes activity by enzymatic method and histopathology of liver using hematoxylin and eosin and TUNEL staining to assess histologic changes and apoptosis in diabetes induced by multiple low doses of streptozotocin (MLDS). RESULTS: The Ala-His, Leu-Gly and Pro-Gly-Pro peptides had the higher protective effects against the effects of diabetes on the enzymes and histologic changes of liver in mice. CONCLUSION: These peptides can be raised as considerable pharmaceutical preventive agent against diabetes development.

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

AIMS/INTRODUCTION: Peptides 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 METHODS: Small 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. RESULTS: The peptides A, Leu-Gly (D) and Pro-Pro showed preventive effects on blood glucose elevation and impairment of the signaling and performance of ß-cells. The ß-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 ß-cells signaling by maintaining the natural balance of intracellular Akt-2 and cyclic adenosine monophosphate. CONCLUSIONS: The 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 ß-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.