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

J Diabetes Investig. 2019 Sep;10(5):1177-1188. doi: 10.1111/jdi.13018. Epub 2019 Mar 12.

Abstract

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 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.

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 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.

Keywords: Glucose; Peptide; β-Cell.

MeSH terms

  • Animals
  • Carnosine / pharmacology*
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Dipeptides / pharmacology*
  • Disease Models, Animal*
  • Male
  • Mice
  • Mice, Inbred BALB C

Substances

  • Dipeptides
  • Carnosine
  • glycylleucine