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

亮氨酸-甘氨酸和肌肽二肽可预防成年小鼠实验模型中多次低剂量链脲佐菌素诱发的糖尿病

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作者:Tohid Vahdatpour, Ali Nokhodchi, Parvin Zakeri-Milani, Mehran Mesgari-Abbasi, Naser Ahmadi-Asl, Hadi Valizadeh

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.

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.

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