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  1. Article ; Online: Ketone bodies: back to a place in the sun.

    Kume, Shinji

    Kidney international

    2021  Volume 100, Issue 5, Page(s) 976–978

    Abstract: Ketone bodies have a strong negative image in medicine because of ketoacidosis, a life-threatening complication in diabetes. However, Fang et al. report that ketone bodies exert antisenescent effects in podocytes under diabetic conditions, via activation ...

    Abstract Ketone bodies have a strong negative image in medicine because of ketoacidosis, a life-threatening complication in diabetes. However, Fang et al. report that ketone bodies exert antisenescent effects in podocytes under diabetic conditions, via activation of the nuclear factor E2-related factor 2-related antioxidative stress pathway. With recent progression of research on longevity, the beneficial effects of ketone bodies are being clarified, and a positive image of ketone bodies is gradually beginning to develop in many research fields including nephrology.
    MeSH term(s) Diabetic Ketoacidosis ; Humans ; Ketone Bodies ; Longevity ; Oxidative Stress
    Chemical Substances Ketone Bodies
    Language English
    Publishing date 2021-10-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2021.07.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 797: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: A novel therapeutic target for kidney diseases: Lessons learned from starvation response.

    Yamahara, Kosuke / Yasuda-Yamahara, Mako / Kume, Shinji

    Pharmacology & therapeutics

    2024  Volume 254, Page(s) 108590

    Abstract: The prevalence of chronic kidney disease (CKD) is increasing worldwide, making the disease an urgent clinical challenge. Caloric restriction has various anti-aging and organ-protective effects, and unraveling its molecular mechanisms may provide insight ... ...

    Abstract The prevalence of chronic kidney disease (CKD) is increasing worldwide, making the disease an urgent clinical challenge. Caloric restriction has various anti-aging and organ-protective effects, and unraveling its molecular mechanisms may provide insight into the pathophysiology of CKD. In response to changes in nutritional status, intracellular nutrient signaling pathways show adaptive changes. When nutrients are abundant, signals such as mechanistic target of rapamycin complex 1 (mTORC1) are activated, driving cell proliferation and other processes. Conversely, others, such as sirtuins and AMP-activated protein kinase, are activated during energy scarcity, in an attempt to compensate. Autophagy, a cellular self-maintenance mechanism that is regulated by such signals, has also been reported to contribute to the progression of various kidney diseases. Furthermore, in recent years, ketone bodies, which have long been considered to be detrimental, have been reported to play a role as starvation signals, and thereby to have renoprotective effects, via the inhibition of mTORC1. Therefore, in this review, we discuss the role of mTORC1, which is one of the most extensively studied nutrient-related signals associated with kidney diseases, autophagy, and ketone body metabolism; and kidney energy metabolism as a novel therapeutic target for CKD.
    MeSH term(s) Humans ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mechanistic Target of Rapamycin Complex 1/pharmacology ; Signal Transduction/physiology ; AMP-Activated Protein Kinases/metabolism ; Kidney/metabolism ; Autophagy ; Renal Insufficiency, Chronic/drug therapy
    Chemical Substances Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; AMP-Activated Protein Kinases (EC 2.7.11.31)
    Language English
    Publishing date 2024-01-28
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 194735-7
    ISSN 1879-016X ; 0163-7258
    ISSN (online) 1879-016X
    ISSN 0163-7258
    DOI 10.1016/j.pharmthera.2024.108590
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1183: Show issues Location:
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  3. Article: Pathophysiological roles of nutrient-sensing mechanisms in diabetes and its complications.

    Kume, Shinji

    Diabetology international

    2019  Volume 10, Issue 4, Page(s) 245–249

    Abstract: Diabetic nephropathy, which is characterized by increased albuminuria, has been the most common cause of end-stage kidney disease for many years in Japan and many other countries. Although the renal prognosis of the disease has been improving in recent ... ...

    Abstract Diabetic nephropathy, which is characterized by increased albuminuria, has been the most common cause of end-stage kidney disease for many years in Japan and many other countries. Although the renal prognosis of the disease has been improving in recent years because of the clinical implementation of strict glucose, blood pressure, and lipid controls, some diabetes patients continue to exhibit treatment-resistant macroalbuminuria leading to end-stage kidney disease. Furthermore, renal function decline without macroalbuminuria in diabetes is an emerging issue in Japan, which might be partly due to aging. Thus, a novel therapeutic strategy is needed to further improve renal outcome in diabetes patients. We have recently reported the involvement of dysregulation of intracellular nutrient-sensing signals and the related cellular process, autophagy, in the pathogenesis of diabetic nephropathy and abnormal insulin secretion pattern in type 2 diabetes. This review discusses potential roles of intracellular nutrient-sensing signals and autophagy as novel therapeutic targets for type 2 diabetes and diabetic nephropathy.
    Language English
    Publishing date 2019-08-13
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2574501-3
    ISSN 2190-1686 ; 2190-1678
    ISSN (online) 2190-1686
    ISSN 2190-1678
    DOI 10.1007/s13340-019-00406-9
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  4. Article ; Online: Nutrient quality in dietary therapy for diabetes and diabetic kidney disease.

    Tsuruta, Hiroaki / Sugahara, Sho / Kume, Shinji

    Journal of diabetes investigation

    2024  

    Abstract: Dietary therapy is crucial for diabetes care with the aim of preventing the onset and progression of diabetes and its complications. The traditional approach to dietary therapy for diabetes has primarily focused on restricting the intake of the three ... ...

    Abstract Dietary therapy is crucial for diabetes care with the aim of preventing the onset and progression of diabetes and its complications. The traditional approach to dietary therapy for diabetes has primarily focused on restricting the intake of the three major nutrients and rigorously controlling blood glucose levels. However, advancements in nutritional science have shown that within the three major nutrients - carbohydrates, proteins and lipids - there exist multiple types, each with distinct impacts on type 2 diabetes and its complications, sometimes even showing conflicting effects. In light of this, the present review shifts its focus from the quantity to the quality of the three major nutrients. It aims to provide an overview of how the differences in nutrient quality can influence onset and progression of type 2 diabetes and diabetic kidney disease, highlighting the diverse effects and, at times, contradictory impacts associated with each nutrient type.
    Language English
    Publishing date 2024-04-09
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 2625840-7
    ISSN 2040-1124 ; 2040-1116
    ISSN (online) 2040-1124
    ISSN 2040-1116
    DOI 10.1111/jdi.14208
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    Zs.A 6920: Show issues Location:
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  5. Article ; Online: A new era of diabetic kidney disease treatment with sodium-glucose cotransporter-2 inhibitors.

    Kume, Shinji / Maegawa, Hiroshi

    Journal of diabetes investigation

    2022  Volume 13, Issue 5, Page(s) 765–767

    Abstract: SGLT2 inhibitors may have a potential to stop the decline of renal function independent of the stage of albuminuria in diabetic kidney disease, and can be a new light in the post-RAS inhibitor era. ...

    Abstract SGLT2 inhibitors may have a potential to stop the decline of renal function independent of the stage of albuminuria in diabetic kidney disease, and can be a new light in the post-RAS inhibitor era.
    MeSH term(s) Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetic Nephropathies/drug therapy ; Female ; Glucose ; Humans ; Kidney ; Male ; Sodium ; Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
    Chemical Substances Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors ; Sodium (9NEZ333N27) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2022-02-03
    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.13747
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    Zs.A 6920: Show issues Location:
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  6. Article ; Online: Emerging Pathophysiological Roles of Ketone Bodies.

    Tsuruta, Hiroaki / Yamahara, Kosuke / Yasuda-Yamahara, Mako / Kume, Shinji

    Physiology (Bethesda, Md.)

    2024  Volume 39, Issue 3

    Abstract: The discovery of insulin approximately a century ago greatly improved the management of diabetes, including many of its life-threatening acute complications like ketoacidosis. This breakthrough saved many lives and extended the healthy lifespan of many ... ...

    Abstract The discovery of insulin approximately a century ago greatly improved the management of diabetes, including many of its life-threatening acute complications like ketoacidosis. This breakthrough saved many lives and extended the healthy lifespan of many patients with diabetes. However, there is still a negative perception of ketone bodies stemming from ketoacidosis. Originally, ketone bodies were thought of as a vital source of energy during fasting and exercise. Furthermore, in recent years, research on calorie restriction and its potential impact on extending healthy lifespans, as well as studies on ketone bodies, have gradually led to a reevaluation of the significance of ketone bodies in promoting longevity. Thus, in this review, we discuss the emerging and hidden roles of ketone bodies in various organs, including the heart, kidneys, skeletal muscles, and brain, as well as their potential impact on malignancies and lifespan.
    MeSH term(s) Humans ; Ketone Bodies ; Ketosis ; Diabetes Mellitus ; Longevity ; Heart
    Chemical Substances Ketone Bodies
    Language English
    Publishing date 2024-01-23
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2158667-6
    ISSN 1548-9221 ; 1548-9213
    ISSN (online) 1548-9221
    ISSN 1548-9213
    DOI 10.1152/physiol.00031.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2164: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Ketone Body Metabolism in Diabetic Kidney Disease.

    Yamahara, Kosuke / Yasuda-Yamahara, Mako / Kuwagata, Shogo / Chin-Kanasaki, Masami / Kume, Shinji

    Kidney360

    2024  Volume 5, Issue 2, Page(s) 320–326

    Abstract: Ketone bodies have a negative image because of ketoacidosis, one of the acute and serious complications in diabetes. The negative image persists despite the fact that ketone bodies are physiologically produced in the liver and serve as an indispensable ... ...

    Abstract Ketone bodies have a negative image because of ketoacidosis, one of the acute and serious complications in diabetes. The negative image persists despite the fact that ketone bodies are physiologically produced in the liver and serve as an indispensable energy source in extrahepatic organs, particularly during long-term fasting. However, accumulating experimental evidence suggests that ketone bodies exert various health benefits. Particularly in the field of aging research, there is growing interest in the potential organoprotective effects of ketone bodies. In addition, ketone bodies have a potential role in preventing kidney diseases, including diabetic kidney disease (DKD), a diabetic complication caused by prolonged hyperglycemia that leads to a decline in kidney function. Ketone bodies may help alleviate the renal burden from hyperglycemia by being used as an alternative energy source in patients with diabetes. Furthermore, ketone body production may reduce inflammation and delay the progression of several kidney diseases in addition to DKD. Although there is still insufficient research on the use of ketone bodies as a treatment and their effects, their renoprotective effects are being gradually proven. This review outlines the ketone body-mediated renoprotective effects in DKD and other kidney diseases.
    MeSH term(s) Humans ; Diabetic Nephropathies ; Ketone Bodies/metabolism ; Ketosis/metabolism ; Diabetes Complications ; Hyperglycemia ; Diabetes Mellitus
    Chemical Substances Ketone Bodies
    Language English
    Publishing date 2024-01-16
    Publishing country United States
    Document type Review ; Journal Article
    ISSN 2641-7650
    ISSN (online) 2641-7650
    DOI 10.34067/KID.0000000000000359
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Lipotoxicity, Nutrient-Sensing Signals, and Autophagy in Diabetic Nephropathy.

    Kume, Shinji / Maegawa, Hiroshi

    JMA journal

    2020  Volume 3, Issue 2, Page(s) 87–94

    Abstract: Diabetic nephropathy is a leading cause of proteinuria, kidney fibrosis, and subsequent end-stage renal disease. The renal prognosis of diabetic patients with refractory proteinuria is extremely poor. Therefore, identification of novel therapeutic ... ...

    Abstract Diabetic nephropathy is a leading cause of proteinuria, kidney fibrosis, and subsequent end-stage renal disease. The renal prognosis of diabetic patients with refractory proteinuria is extremely poor. Therefore, identification of novel therapeutic targets to combat this serious condition and improve renal prognosis is urgently necessary. In diabetic patients, in addition to blood glucose levels, serum levels of free fatty acids (FFAs) are chronically elevated, even during postprandial periods. Of the various types of FFAs, saturated FFAs are highly cytotoxic and their levels are elevated in the serum of patients with diabetes. Thus, an increase in saturated FFAs is currently thought to contribute to proximal tubular cell damage and podocyte injury in diabetic nephropathy. Therefore, protecting both types of kidney cells from saturated FFA-related lipotoxicity may become a novel therapeutic approach for diabetic patients with refractory proteinuria. Interestingly, accumulating evidence suggests that controlling intracellular nutrient signals and autophagy can ameliorate the FFA-related kidney damage. Here, we review the evidence indicating possible mechanisms underlying cell injury caused by saturated FFAs and cell protective roles of intracellular nutrient signals and autophagy in diabetic nephropathy.
    Language English
    Publishing date 2020-04-07
    Publishing country Japan
    Document type Journal Article ; Review
    ISSN 2433-3298
    ISSN (online) 2433-3298
    DOI 10.31662/jmaj.2020-0005
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  9. Article: Roles of mTOR in Diabetic Kidney Disease.

    Yasuda-Yamahara, Mako / Kume, Shinji / Maegawa, Hiroshi

    Antioxidants (Basel, Switzerland)

    2021  Volume 10, Issue 2

    Abstract: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and the number of patients affected is increasing worldwide. Thus, there is a need to establish a new treatment for DKD to improve the renal prognosis of diabetic patients. ... ...

    Abstract Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and the number of patients affected is increasing worldwide. Thus, there is a need to establish a new treatment for DKD to improve the renal prognosis of diabetic patients. Recently, it has shown that intracellular metabolic abnormalities are involved in the pathogenesis of DKD. In particular, the activity of mechanistic target of rapamycin complex 1 (mTORC1), a nutrient-sensing signaling molecule, is hyperactivated in various organs of diabetic patients, which suggests the involvement of excessive mTORC1 activation in the pathogenesis of diabetes. In DKD, hyperactivated mTORC1 may be involved in the pathogenesis of podocyte damage, which causes proteinuria, and tubular cell injury that decreases renal function. Therefore, elucidating the role of mTORC1 in DKD and developing new therapeutic agents that suppress mTORC1 hyperactivity may shed new light on DKD treatments in the future.
    Language English
    Publishing date 2021-02-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10020321
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Roles of mTOR in Diabetic Kidney Disease

    Yasuda-Yamahara, Mako / Kume, Shinji / Maegawa, Hiroshi

    Antioxidants. 2021 Feb. 22, v. 10, no. 2

    2021  

    Abstract: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and the number of patients affected is increasing worldwide. Thus, there is a need to establish a new treatment for DKD to improve the renal prognosis of diabetic patients. ... ...

    Abstract Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and the number of patients affected is increasing worldwide. Thus, there is a need to establish a new treatment for DKD to improve the renal prognosis of diabetic patients. Recently, it has shown that intracellular metabolic abnormalities are involved in the pathogenesis of DKD. In particular, the activity of mechanistic target of rapamycin complex 1 (mTORC1), a nutrient-sensing signaling molecule, is hyperactivated in various organs of diabetic patients, which suggests the involvement of excessive mTORC1 activation in the pathogenesis of diabetes. In DKD, hyperactivated mTORC1 may be involved in the pathogenesis of podocyte damage, which causes proteinuria, and tubular cell injury that decreases renal function. Therefore, elucidating the role of mTORC1 in DKD and developing new therapeutic agents that suppress mTORC1 hyperactivity may shed new light on DKD treatments in the future.
    Keywords diabetes ; kidney diseases ; pathogenesis ; prognosis ; proteinuria ; rapamycin ; renal function ; therapeutics
    Language English
    Dates of publication 2021-0222
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10020321
    Database NAL-Catalogue (AGRICOLA)

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