Hypoglycemic dipeptide cyclo (His-Pro) significantly altered plasma proteome in streptozocin-induced diabetic rats and genetically-diabetic (ob/ob) mice

Abstract

The proteins in plasma perform many important functions in the body, and the protein profiles of the plasma vary under different physiological and pathological conditions. In an attempt to identify novel marker proteins for diabetes prognosis, we examined the effect of hypoglycemic dipeptide cyclo (His-Pro) (CHP) on the differential regulation of plasma proteins in streptozocin-induced diabetic rats and genetically-diabetic (ob/ob) mice. The orally-administrated CHP produced an excellent hypoglycemic effect in both animal models, lowering the average plasma glucose level by over 50 %. In the 2-DE analysis of the plasma, a total of 23 spots among 500 visualized spots were found to be differentially regulated, and they were identified by MALDI/TOF mass spectrometry. These proteins include the down-regulation of Apo E and the up-regulation of FGA, Apo A-I, Apo A-IV, and A1M in STZ-induced diabetic rats. Moreover, CHP significantly reduced the plasma protein levels of FGB, FGC, F12, C1QTNF5, and SPA3K, as well as increased the abundance of A1M, A2M, Apo E, and TTR in genetically-diabetic mice. In conclusion, alteration in the regulation of these proteins indicates that this treatment may be successful in overcoming the diabetic state. The present proteomic data can serve as the basis for the development of specific evidence-based interventions allowing for the prevention and treatment of diabetes.

In silicoanalysis ofTTRgene (coding and non-coding regions, and interactive network) and its implications in transthyretin-related amyloidosis

“…This may have a relevant impact in disease presentation: alteration of AbPP activity may modulate the amyloidogenic process caused by TTR mutations. As for APOA1, the TTR-FGA interaction seems to be due by dietary alterations: animal experiments with MALDI/TOF mass spectrometry indicated that diabetic rats showed altered proteomic profile, in which FGA and TTR are also included [53]. Our bioinformatic analysis and the data available in literature suggest that these proteins may be involved in the pathogenesis of TTR-related amyloidosis, along with the pathways indicated.…”

Mediation analysis of chronic kidney disease risk factors using kidney biomarkers in women living with HIV

“…A more recent study of HIV-1 proviral gene expression in murine podocytes confirmed mechanisms of glomerulopathy and further showed that concurrent HIV and diabetes were associated with increased acetylation which enhanced expression of senescence and inflammatory markers [39]. A proteomics study also showed elevated plasma levels of a1m in genetically-diabetic mice compared to control mice, and an increasing number of studies have demonstrated the role of proximal tubule injury in both murine and human diabetic renal cells [40,41].…”

Prevention and Treatment of Obesity and Diabetes and their Related Complications

“…In general its side effects are irritation of stomach other than megadose of more than 1 g of zinc element which could induce serious pathological condition and fatal if taken more than 10 g at a time. CHP side effects are not well established without any report of side effects but some studies of anti-toxicity of CHP have been published [100,117,118]. The long term side effect in humans will be established in our long term clinical trial and in the toxicological studies in dogs with high dose of Cyclo-Z for one year.…”

“…Cyclo-Z enhances IDE synthesis and stimulates insulin degradation ( Figure 13). In addition, CHP enhances gene expression of factors that ameliorate diabetes and antagonizes factors that induce diabetes [100]. Although CHP or zinc alone is somewhat effective in the control of blood glucose metabolism, Cyclo-Z may be the most effective agent in ameliorating insulin resistance in diabetes and obesity since it stimulates IDE synthesis and enhances beneficial gene expression for diabetes improvement.…”