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  1. Article ; Online: Diabetic kidney disease: Its current trends and future therapeutic perspectives.

    Koya, Daisuke

    Journal of diabetes investigation

    2019  Volume 10, Issue 5, Page(s) 1174–1176

    MeSH term(s) Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Glucose ; Humans ; Renal Insufficiency, Chronic ; Sodium
    Chemical Substances Sodium (9NEZ333N27) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2019-08-22
    Publishing country Japan
    Document type Journal Article ; Comment
    ZDB-ID 2625840-7
    ISSN 2040-1124 ; 2040-1116
    ISSN (online) 2040-1124
    ISSN 2040-1116
    DOI 10.1111/jdi.13121
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    Zs.A 6920: Show issues Location:
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  2. Article ; Online: The Role of CD38 in the Pathogenesis of Cardiorenal Metabolic Disease and Aging, an Approach from Basic Research.

    Kitada, Munehiro / Araki, Shin-Ichi / Koya, Daisuke

    Cells

    2023  Volume 12, Issue 4

    Abstract: Aging is a major risk factor for the leading causes of mortality, and the incidence of age-related diseases including cardiovascular disease, kidney disease and metabolic disease increases with age. ... ...

    Abstract Aging is a major risk factor for the leading causes of mortality, and the incidence of age-related diseases including cardiovascular disease, kidney disease and metabolic disease increases with age. NAD
    MeSH term(s) Humans ; ADP-ribosyl Cyclase 1/metabolism ; Inflammation ; Metabolic Diseases/metabolism ; Metabolic Diseases/pathology ; NAD/metabolism ; Aging/metabolism ; Aging/pathology
    Chemical Substances ADP-ribosyl Cyclase 1 (EC 3.2.2.6) ; NAD (0U46U6E8UK) ; CD38 protein, human (EC 3.2.2.5)
    Language English
    Publishing date 2023-02-12
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12040595
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  3. Article ; Online: Impact of empagliflozin on diabetic kidney disease.

    Koya, Daisuke

    Journal of diabetes investigation

    2017  Volume 8, Issue 5, Page(s) 658–660

    Abstract: Empaglifolzin reduces metabolic derangements such as BP (blood pressure), hyperglycemia, body weight, uric acid, increases Ht (hamtaocrit), keton bodies, and restores altered tubule-glomerular feedback, thereby protect against diabetes-induced caidio- ... ...

    Abstract Empaglifolzin reduces metabolic derangements such as BP (blood pressure), hyperglycemia, body weight, uric acid, increases Ht (hamtaocrit), keton bodies, and restores altered tubule-glomerular feedback, thereby protect against diabetes-induced caidio-renal injuries.
    Language English
    Publishing date 2017-09
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2625840-7
    ISSN 2040-1124 ; 2040-1116
    ISSN (online) 2040-1124
    ISSN 2040-1116
    DOI 10.1111/jdi.12615
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  4. Article ; Online: Autophagy in metabolic disease and ageing.

    Kitada, Munehiro / Koya, Daisuke

    Nature reviews. Endocrinology

    2021  Volume 17, Issue 11, Page(s) 647–661

    Abstract: Autophagy is an evolutionarily conserved, lysosome-dependent catabolic process whereby cytoplasmic components, including damaged organelles, protein aggregates and lipid droplets, are degraded and their components recycled. Autophagy has an essential ... ...

    Abstract Autophagy is an evolutionarily conserved, lysosome-dependent catabolic process whereby cytoplasmic components, including damaged organelles, protein aggregates and lipid droplets, are degraded and their components recycled. Autophagy has an essential role in maintaining cellular homeostasis in response to intracellular stress; however, the efficiency of autophagy declines with age and overnutrition can interfere with the autophagic process. Therefore, conditions such as sarcopenic obesity, insulin resistance and type 2 diabetes mellitus (T2DM) that are characterized by metabolic derangement and intracellular stresses (including oxidative stress, inflammation and endoplasmic reticulum stress) also involve the accumulation of damaged cellular components. These conditions are prevalent in ageing populations. For example, sarcopenia is an age-related loss of skeletal muscle mass and strength that is involved in the pathogenesis of both insulin resistance and T2DM, particularly in elderly people. Impairment of autophagy results in further aggravation of diabetes-related metabolic derangements in insulin target tissues, including the liver, skeletal muscle and adipose tissue, as well as in pancreatic β-cells. This Review summarizes the role of autophagy in the pathogenesis of metabolic diseases associated with or occurring in the context of ageing, including insulin resistance, T2DM and sarcopenic obesity, and describes its potential as a therapeutic target.
    MeSH term(s) Aged ; Aging/pathology ; Autophagy ; Diabetes Mellitus, Type 2/pathology ; Humans ; Insulin Resistance ; Metabolic Diseases/pathology ; Obesity/pathology ; Sarcopenia/pathology
    Language English
    Publishing date 2021-09-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2489381-X
    ISSN 1759-5037 ; 1759-5029
    ISSN (online) 1759-5037
    ISSN 1759-5029
    DOI 10.1038/s41574-021-00551-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Epidermal growth factor receptor signaling and the progression of diabetic nephropathy.

    Koya, Daisuke

    Journal of diabetes investigation

    2015  Volume 6, Issue 5, Page(s) 519–521

    Language English
    Publishing date 2015-09
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2625840-7
    ISSN 2040-1124 ; 2040-1116
    ISSN (online) 2040-1124
    ISSN 2040-1116
    DOI 10.1111/jdi.12317
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  6. Article: Proposal of classification of "chronic kidney disease (CKD) with diabetes" in clinical setting.

    Kitada, Munehiro / Koya, Daisuke

    Diabetology international

    2019  Volume 10, Issue 3, Page(s) 180–182

    Abstract: The natural history of typical and classical "diabetic nephropathy" has been described as high levels of albuminuria and subsequent renal function decline. However, recent decades, the cases, who show the reduced glomerular filtration rate (GFR) without ... ...

    Abstract The natural history of typical and classical "diabetic nephropathy" has been described as high levels of albuminuria and subsequent renal function decline. However, recent decades, the cases, who show the reduced glomerular filtration rate (GFR) without the progression of albuminuria, has been increased. "Diabetic kidney disease (DKD)" is a concept that widely recognizes the pathophysiological change induced by diabetes as the onset and progressive factor of renal injury and renal function decline, regardless of the level of albuminuria. However, we may confuse that "chronic kidney disease (CKD) with diabetes" is "DKD". Therefore, to choose the appropriate treatment that should be prioritized in the clinical setting, we propose that "CKD with diabetes" is classified as "DKD", "non-DKD (NDKD) with diabetes" or "combined disease of DKD and NDKD".
    Language English
    Publishing date 2019-04-29
    Publishing country Japan
    Document type Editorial
    ZDB-ID 2574501-3
    ISSN 2190-1686 ; 2190-1678
    ISSN (online) 2190-1686
    ISSN 2190-1678
    DOI 10.1007/s13340-019-00396-8
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  7. Article: Inhibition of Dipeptidyl Peptidase-4 Activates Autophagy to Promote Survival of Breast Cancer Cells via the mTOR/HIF-1α Pathway.

    Kawakita, Emi / Yang, Fan / Shi, Sen / Takagaki, Yuta / Koya, Daisuke / Kanasaki, Keizo

    Cancers

    2023  Volume 15, Issue 18

    Abstract: Autophagy plays a complex role in breast cancer cell survival, metastasis, and chemotherapeutic resistance. Dipeptidyl peptidase (DPP)-4, a therapeutic target for type 2 diabetes mellitus, is also involved in autophagic flux. The potential influence of ... ...

    Abstract Autophagy plays a complex role in breast cancer cell survival, metastasis, and chemotherapeutic resistance. Dipeptidyl peptidase (DPP)-4, a therapeutic target for type 2 diabetes mellitus, is also involved in autophagic flux. The potential influence of DPP-4 suppression on cancer biology remains unknown. Here, we report that DPP-4 deficiency promotes breast cancer cell survival via the induction of autophagy by the C-X-C motif chemokine 12 (CXCL12)/C-X-C receptor 4 (CXCR4)/mammalian target of rapamycin (mTOR)/hypoxia inducible factor (HIF)-1α axis. DPP-4 knockdown and DPP-4 inhibitor KR62436 (KR) treatment both increased the levels of LC3II and HIF-1α in cultured human breast and mouse mammary cancer cells. The KR-induced autophagic phenotype in cancer cells was inhibited by treatment with the CXCR4 inhibitor AMD3100 and rapamycin. HIF-1α knockdown also suppressed breast cancer autophagy induced by KR. The autophagy inhibitor 3-methyladenine significantly blocked the KR-mediated suppression of cleaved caspase-3 levels and apoptosis in breast cancer cell lines. Finally, we found that the metformin-induced apoptosis of DPP-4-deficient 4T1 mammary cancer cells was associated with the suppression of autophagy. Our findings identify a novel role for DPP-4 inhibition in the promotion of breast cancer survival by inducing CXCL12/CXCR4/mTOR/HIF-1α axis-dependent autophagy. Metformin is a potential drug that counteracts the breast cancer cell survival system.
    Language English
    Publishing date 2023-09-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15184529
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  8. Article: Diabetic nephropathy: advances in treatment.

    Kitada, Munehiro / Koya, Daisuke

    Nihon Jinzo Gakkai shi

    2019  Volume 59, Issue 2, Page(s) 74–78

    MeSH term(s) Diabetic Nephropathies/therapy ; Humans
    Language Japanese
    Publishing date 2019-01-02
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1195538-7
    ISSN 0385-2385
    ISSN 0385-2385
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    Zs.A 1383: Show issues Location:
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  9. Article: Diabetic nephropathy

    Kitada, Munehiro / Koya, Daisuke

    Nihon Jinzo Gakkai shi

    2019  Volume 59, Issue 2, Page(s) 38–42

    MeSH term(s) Diabetic Nephropathies ; Humans
    Language Japanese
    Publishing date 2019-01-02
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1195538-7
    ISSN 0385-2385
    ISSN 0385-2385
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  10. Article ; Online: Linagliptin ameliorated cardiac fibrosis and restored cardiomyocyte structure in diabetic mice associated with the suppression of necroptosis.

    Adhikari, Juthi / Hirai, Taro / Kawakita, Emi / Iwai, Kunimitsu / Koya, Daisuke / Kanasaki, Keizo

    Journal of diabetes investigation

    2023  Volume 14, Issue 7, Page(s) 844–855

    Abstract: Aims/introduction: Linagliptin is a selective dipeptidyl peptidase (DPP)-4 inhibitor capable of successfully regulating blood glucose levels. The cardiovascular protective effects of several DPP-4 inhibitors have been shown in preclinical studies; ... ...

    Abstract Aims/introduction: Linagliptin is a selective dipeptidyl peptidase (DPP)-4 inhibitor capable of successfully regulating blood glucose levels. The cardiovascular protective effects of several DPP-4 inhibitors have been shown in preclinical studies; however, the detailed influence of DPP-4 inhibitors on diabetic pathological alterations in cardiac tissue has not yet been elucidated.
    Materials and methods: We combined laboratory-based experiments and bioinformatics techniques to identify suitable candidate targets with significant biological pathways. Mice with streptozotocin-induced insulin deficiency diabetic model were utilized for in vivo experiments. Mice were euthanized at 24 weeks after the induction of diabetes; linagliptin intervention was carried out for 4 weeks before euthanasia. Microarray analysis of heart samples was carried out.
    Results: Mice with streptozotocin-induced diabetes, but not control mice, showed cardiac fibrosis with an endothelial-mesenchymal transition program, and myocardial fiber and sarcomere disruption; linagliptin alleviated these diabetes-associated pathological alterations without altering blood glucose levels. Bioinformatics analysis utilizing a microarray dataset identified 10 hub genes that were confirmed to have human disease relevance by Gene Expression Omnibus analysis. Among these hub genes, we focused on the Sox9-necroptosis axis as a therapeutic target in diabetic hearts. Indeed, diabetic mice showed the induction of necroptosis-associated genes and the phosphorylation of RIP3 and mixed lineage kinase domain-like protein.
    Conclusions: Linagliptin showed excellent heart protection in mice with streptozotocin-induced diabetes associated with alterations in human disease-relevant hub genes. Further investigation is required to determine why DPP-4 inhibitors do not show similar superior organ-protective effects in the clinical setting.
    MeSH term(s) Humans ; Mice ; Animals ; Linagliptin/pharmacology ; Linagliptin/therapeutic use ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/drug therapy ; Diabetes Mellitus, Experimental/pathology ; Myocytes, Cardiac/metabolism ; Blood Glucose ; Streptozocin ; Necroptosis ; Hypoglycemic Agents/therapeutic use ; Fibrosis ; Dipeptidyl Peptidase 4
    Chemical Substances Linagliptin (3X29ZEJ4R2) ; Dipeptidyl-Peptidase IV Inhibitors ; Blood Glucose ; Streptozocin (5W494URQ81) ; Hypoglycemic Agents ; Dipeptidyl Peptidase 4 (EC 3.4.14.5)
    Language English
    Publishing date 2023-04-24
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2625840-7
    ISSN 2040-1124 ; 2040-1116
    ISSN (online) 2040-1124
    ISSN 2040-1116
    DOI 10.1111/jdi.14017
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