| Summary: | W. Riski Widya Mulyani,1 Made Indira Dianti Sanjiwani,1 Sandra,1 I Putu Yuda Prabawa,2 Anak Agung Wiradewi Lestari,2 Desak Made Wihandani,3 Ketut Suastika,4 Made Ratna Saraswati,4 Agha Bhargah,1,5 Ida Bagus Amertha Putra Manuaba6,7 1Faculty of Medicine, Universitas Udayana, Bali, Indonesia; 2Department of Clinical Pathology, Faculty of Medicine, Universitas Udayana, Sanglah General Hospital, Bali, Indonesia; 3Department of Biochemistry, Faculty of Medicine, Universitas Udayana, Bali, Indonesia; 4Department of Internal Medicine, Faculty of Medicine, Universitas Udayana, Sanglah General Hospital, Bali, Indonesia; 5Cardiology Department, Faculty of Medicine, Universitas Udayana-Sanglah General Hospital, Bali, Indonesia; 6International Ph.D Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 7Medical and Health Education Unit, Faculty of Medicine, Universitas Udayana, Bali, IndonesiaCorrespondence: Anak Agung Wiradewi LestariDepartment of Clinical Pathology, Faculty of Medicine, Universitas Udayana, Sanglah General Hospital, Bali, IndonesiaEmail wiradewilestari@gmail.comAbstract: 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.Keywords: type 2 diabetes mellitus, HSP70, insulin resistance
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