Alterations in Pancreatic Protein Expression in STZ-Induced Diabetic Rats and Genetically Diabetic Mice in Response to Treatment with Hypoglycemic Dipeptide Cyclo (His-Pro)

Abstract

To provide insights into the molecular mechanisms underlying diabetes mellitus, we performed a proteomic study on two diabetic animal models, streptozotocin (STZ)-induced diabetic rats (T1DM) and genetically diabetic (C57BL/6J ob/ob) mice (T2DM). To better understand the recovery process of those diabetic rodents, we examined the effect of hypoglycemic dipeptide Cyclo (His-Pro) (CHP) treatment on the differential expression of pancreatic proteins in both animal models. Oral administration of CHP had an excellent hypoglycemic effect in both animal models, lowering the average plasma glucose level by over 50%. Pancreatic proteins were separated by two-dimensional gel electrophoresis (2-DE) and identified by MALDI-TOF mass spectrometry. This study allowed, for the first time, the identification of 34 proteins that are related to diabetes and potential targets of CHP, a potent anti-diabetic agent for both T1DM and T2DM. The alterations in the expression of these proteins could indicate a tendency for diabetic animals to overcome their diabetic state. These proteins are involved in cellular functions such as metabolism, cellular structure, oxidative stress, as well as signal and energy transduction. Some have already been linked to diabetes, suggesting that the newly identified proteins might also be significant in the etiology of this pathology and should be further investigated. Furthermore, CHP has emerged as a potent tool for both the treatment and study of the molecular mechanisms underlying diabetes. Thus, the findings presented here provide new insights into the study and potential treatment of this pathology.

Modulation of Oxidative Stress and Apoptosis by Alteration of Bioactive Lipids in The Pancreas, and Effect of Zinc Chelation in a Rat Model of Alzheimer's Disease

“…However, no difference was found in the AIPP and caspase-3 levels of the SHC group compared to the SH group. The CHP therapeutic agent has also been shown to reduce oxidative stress in the pancreas in an STZ-induced rat model [55]. In our study, pancreatic TOS levels of the ADC group decreased signi cantly compared to the AD group, and 4HNE levels tended to decrease.…”

Anti-Diabetic Effects of the Ethyl-Acetate Fraction of Trichilia catigua in Streptozo-tocin-Induced Type 1 Diabetic Rats

“…Type 1 DM is characterized by pancreatic β-cell apoptosis and massive reduction in the number and area of the pancreatic islets [1][2][3]. In 2015 alone, this pathology affected 415 million people worldwide, caused 5.0 million deaths and cost 673 billion dollars from public coffers worldwide [4].…”

Cyclic Peptides in Neurological Disorders: The Case of Cyclo(His-Pro)

“…CDPs released by the coldwater marine sponge Geodia barretti synergistically exert chemical defense (Sj€ ogren et al, 2011). Moreover, CHP, a catabolic product of TRH (thyrotropin releasing hormone), can control blood glucose levels Jung et al, 2011Jung et al, , 2016Koo et al, 2011;Lee et al, , 2013Park et al, 2012) and, associated to zinc, has already been patented in the United States as an antidiabetic drug with no side effects in humans (Uyemura et al, 2010).…”