Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes Mellitus

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; 2Departm...

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Main Authors: Mulyani WRW, Sanjiwani MID, Sandra, Prabawa IPY, Lestari AAW, Wihandani DM, Suastika K, Saraswati MR, Bhargah A, Manuaba IBAP
Format: Article
Language:English
Published: Dove Medical Press 2020-02-01
Series:Diabetes, Metabolic Syndrome and Obesity
Subjects:
Online Access:https://www.dovepress.com/chaperone-based-therapeutic-target-innovation-heat-shock-protein-70-hs-peer-reviewed-article-DMSO
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author Mulyani WRW
Sanjiwani MID
Sandra
Prabawa IPY
Lestari AAW
Wihandani DM
Suastika K
Saraswati MR
Bhargah A
Manuaba IBAP
author_facet Mulyani WRW
Sanjiwani MID
Sandra
Prabawa IPY
Lestari AAW
Wihandani DM
Suastika K
Saraswati MR
Bhargah A
Manuaba IBAP
author_sort Mulyani WRW
collection DOAJ
description 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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spelling doaj.art-8ce3edd7ec944ce28679c9254fdc6a7a2023-02-02T09:57:49ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072020-02-01Volume 1355956852124Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes MellitusMulyani WRWSanjiwani MIDSandraPrabawa IPYLestari AAWWihandani DMSuastika KSaraswati MRBhargah AManuaba IBAPW. 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 resistancehttps://www.dovepress.com/chaperone-based-therapeutic-target-innovation-heat-shock-protein-70-hs-peer-reviewed-article-DMSOtype 2 diabetes mellitushsp70insulin resistance.
spellingShingle Mulyani WRW
Sanjiwani MID
Sandra
Prabawa IPY
Lestari AAW
Wihandani DM
Suastika K
Saraswati MR
Bhargah A
Manuaba IBAP
Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes Mellitus
Diabetes, Metabolic Syndrome and Obesity
type 2 diabetes mellitus
hsp70
insulin resistance.
title Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes Mellitus
title_full Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes Mellitus
title_fullStr Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes Mellitus
title_full_unstemmed Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes Mellitus
title_short Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes Mellitus
title_sort chaperone based therapeutic target innovation heat shock protein 70 hsp70 for type 2 diabetes mellitus
topic type 2 diabetes mellitus
hsp70
insulin resistance.
url https://www.dovepress.com/chaperone-based-therapeutic-target-innovation-heat-shock-protein-70-hs-peer-reviewed-article-DMSO
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