{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T20:24:39Z","timestamp":1772655879226,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T00:00:00Z","timestamp":1553558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) is associated with pancreatic \u03b2-cell dysfunction which can be induced by oxidative stress. Deuterohemin-\u03b2Ala-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.<\/jats:p>","DOI":"10.3390\/ijms20061517","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T05:03:12Z","timestamp":1553662992000},"page":"1517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2376-9854","authenticated-orcid":false,"given":"Kai","family":"Wang","sequence":"first","affiliation":[{"name":"School of life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Su","sequence":"additional","affiliation":[{"name":"School of life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Liang","sequence":"additional","affiliation":[{"name":"School of life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhui","family":"Song","sequence":"additional","affiliation":[{"name":"School of life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Wang","sequence":"additional","affiliation":[{"name":"School of life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/iub.1396","article-title":"Type-2 diabetes: Current understanding and future perspectives","volume":"67","author":"Pandey","year":"2015","journal-title":"IUBMB Life"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.biopha.2018.06.085","article-title":"Therapeutic effect of vitamin B3 on hyperglycemia, oxidative stress and DNA damage in alloxan induced diabetic rat model","volume":"105","author":"Abdullah","year":"2018","journal-title":"Biomed. 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