Open Access<p>Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes Mellitus</p>
Author(s) -
W. Riski Widya Mulyani,
Made Indira Dianti Sanjiwani,
; Sandra,
I Putu Yuda Prabawa,
Anak Agung Wiradewi Lestari,
Desak Made Wihandani,
Ketut Suastika,
Made Ratna Saraswati,
Agha Bhargah,
Ida Bagus Putra Manuaba
Publication year - 2020
Publication title -
diabetes, metabolic syndrome and obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.853
H-Index - 43
ISSN - 1178-7007
DOI - 10.2147/dmso.s232133
Subject(s) - hsp70 , insulin resistance , mitophagy , type 2 diabetes mellitus , heat shock protein , chaperone (clinical) , type 2 diabetes , insulin , mitochondrial biogenesis , glycemic , inflammation , biology , endocrinology , mitochondrion , medicine , diabetes mellitus , microbiology and biotechnology , gene , biochemistry , autophagy , apoptosis , pathology
Type 2 diabetes mellitus (T2DM) is still a global health problem. Current T2DM treatments are limited to curing the symptoms and have not been able to restore insulin sensitivity in insulin-sensitive tissues that have become resistant. In the past decade, some studies have shown the significant role of a chaperone family, heat shock protein 70 (HSP70), in insulin resistance pathogenesis that leads to T2DM. HSP70 is a cytoprotective molecular chaperone that functions in protein folding and degradation. In general, studies have shown that decreased concentration of HSP70 is able to induce inflammation process through JNK activation, inhibit fatty acid oxidation by mitochondria through mitophagy decrease and mitochondrial biogenesis, as well as activate SREBP-1c, one of the lipogenic gene transcription factors in ER stress. The overall molecular pathways are potentially leading to insulin resistance and T2DM. Increased expression of HSP70 in brain tissues is able to improve insulin sensitivity and glycemic control specifically. HSP70 modulation-targeting strategies (including long-term physical exercise, hot tub therapy (HTT), and administration of alfalfa-derived HSP70 (aHSP70)) in subjects with insulin resistance are proven to have therapeutic and preventive potency that are promising in T2DM management.