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

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.

Deteriorating insulin resistance due to WL15 peptide from cysteine and glycine‐rich protein 2 in high glucose‐induced rat skeletal muscle L6 cells

“…This peptide was able to reduce intracellular oxidative stress and upregulated the expression of antioxidant enzyme genes in zebrafish larvae models (Guru et al, 2021). WL15 peptide has leucine and glycine in its peptide sequence, and these amino acids have been reported to prevent the progression of diabetes (Vahdatpour et al, 2019), so it has been hypothesized that WL15 peptide could also have antidiabetic properties.…”

“…This peptide was able to reduce intracellular oxidative stress and upregulated the expression of antioxidant enzyme genes in zebrafish larvae models (Guru et al, 2021). WL15 peptide has leucine and glycine in its peptide sequence, and these amino acids have been reported to prevent the progression of diabetes (Vahdatpour et al, 2019), so it has been hypothesized that WL15 peptide could also have antidiabetic properties. The objective of this study was to investigate the antioxidant potential of WL15 peptide in insulin resistance mediated oxidative damage in L6 cells induced by 25 mM glucose and to determine the ability of WL15 peptide to augment glucose uptake and enhance glucose utilization by increasing the expression of GLUT4 in L6 cells.…”

Metabolomic shifts associated with heat stress in coral holobionts

“…However, an accumulation of proteogenic dipeptides during a time course stress experiment is linked to autophagy in Arabidopsis thaliana (26). Dipeptides also serve a diversity of other functions such as small-molecule regulators [e.g., H + buffers (27), antioxidants (28), and glucose regulators (29)]. RQ has been shown to ameliorate the impacts of oxygen imbalance in retinopathy of prematurity in murine models (30) and may have beneficial effects on the reversal of oxygen-induced lung damage (31).…”

Purification and characterization of hypoglycemic peptides from traditional Chinese soy-fermented douchi

“…The presence of Leu (L), Val (V), and Pro (P) is important since they contribute to the observed effects; for example, Leu was considered a key contributor to the inhibition effect against α-glucosidase, 37 and Leu and Pro had positive effects on blood glucose regulation and the signaling and performance of β-cells. 38 Further identification of new bioactive peptides within food proteins will help us understand the structure-function relationship.…”