Next Article in Journal
X-linked Retinitis Pigmentosa in Japan: Clinical and Genetic Findings in Male Patients and Female Carriers
Next Article in Special Issue
Identification of a Novel Oligosaccharide in Maple Syrup as a Potential Alternative Saccharide for Diabetes Mellitus Patients
Previous Article in Journal
Computational Study for the Unbinding Routes of β-N-Acetyl-d-Hexosaminidase Inhibitor: Insight from Steered Molecular Dynamics Simulations
Open AccessArticle

Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

1
School of life Sciences, Jilin University, Changchun 130012, China
2
Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, Jilin University, Changchun 130012, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(6), 1517; https://doi.org/10.3390/ijms20061517
Received: 24 February 2019 / Revised: 15 March 2019 / Accepted: 22 March 2019 / Published: 26 March 2019
(This article belongs to the Special Issue Nutrition and Diabetes)
Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction which can be induced by oxidative stress. Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy. View Full-Text
Keywords: type 2 diabetes mellitus; Deuterohemin-βAla-His-Thr-Val-Glu-Lys; high stability; anti-diabetic drug type 2 diabetes mellitus; Deuterohemin-βAla-His-Thr-Val-Glu-Lys; high stability; anti-diabetic drug
Show Figures

Figure 1

MDPI and ACS Style

Wang, K.; Su, Y.; Liang, Y.; Song, Y.; Wang, L. Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus. Int. J. Mol. Sci. 2019, 20, 1517.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop