Background Heart failure is responsible for approximately 65% of deaths in patients with type 2 diabetes mellitus. However, existing therapeutics for type 2 diabetes mellitus have limited success on the prevention of diabetic cardiomyopathy. The aim of this study was to determine whether moderate elevation in D-β-hydroxybutyrate improves cardiac function in animals with type 2 diabetes mellitus. Methods and Results Type 2 diabetic (db/db) and their corresponding wild-type mice were fed a control diet or a diet where carbohydrates were equicalorically replaced by D-β-hydroxybutyrate-(R)-1,3 butanediol monoester (ketone ester [KE]). After 4 weeks, echocardiography demonstrated that a KE diet improved systolic and diastolic function in db/db mice. A KE diet increased expression of mitochondrial succinyl-CoA:3-oxoacid-CoA transferase and restored decreased expression of mitochondrial β-hydroxybutyrate dehydrogenase, key enzymes in cardiac ketone metabolism. A KE diet significantly enhanced both basal and ADP-mediated oxygen consumption in cardiac mitochondria from both wild-type and db/db animals; however, it did not result in the increased mitochondrial respiratory control ratio. Additionally, db/db mice on a KE diet had increased resistance to oxidative and redox stress, with evidence of restoration of decreased expression of thioredoxin and glutathione peroxidase 4 and less permeability transition pore activity in mitochondria. Mitochondrial biogenesis, quality control, and elimination of dysfunctional mitochondria via mitophagy were significantly increased in cardiomyocytes from db/db mice on a KE diet. The increase in mitophagy was correlated with restoration of mitofusin 2 expression, which contributed to improved coupling between cytosolic E3 ubiquitin ligase translocation into mitochondria and microtubule-associated protein 1 light chain 3-mediated autophagosome formation. Conclusions Moderate elevation in circulating D-β-hydroxybutyrate levels via KE supplementation enhances mitochondrial biogenesis, quality control, and oxygen consumption and increases resistance to oxidative/redox stress and mPTP opening, thus resulting in improvement of cardiac function in animals with type 2 diabetes mellitus.
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http://dx.doi.org/10.1161/JAHA.120.020729 | DOI Listing |
Diabetes
January 2025
Department of Big Data in Health Science, Zhejiang University School of Public Health and Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Clonal haematopoiesis of indeterminate potential (CHIP) is associated with macrovascular diseases, including coronary artery disease and stroke. However, the effects of CHIP on microvascular complication have not been evaluated in individuals with type 2 diabetes (T2D). This study included 20,712 T2D participants without prevalent diabetic microvascular complication (DMCs) and hematologic malignancy at baseline.
View Article and Find Full Text PDFJ Mater Chem B
January 2025
Key Laboratory of Marine Drugs, Ministry of Education; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Amyloidosis of the human islet amyloid polypeptide (hIAPP) is closely related to the pathogenesis of type 2 diabetes (T2D) and serves as both a diagnostic hallmark and a key therapeutic target for T2D. In this study, we discovered that oritavancin (Ori), a glycopeptide antibiotic primarily prescribed for Gram-positive bacterial infections, can dose-dependently inhibit recombinant hIAPP (rhIAPP) amyloid formation. Ori specifically inhibited rhIAPP amyloid formation at the initial nucleation stage but didn't affect mature rhIAPP fibrils.
View Article and Find Full Text PDFLangenbecks Arch Surg
January 2025
Department of Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Hospital, Leipzig, Germany.
Purpose: Obesity and type 2 diabetes (T2DM) are major risk factors for hepatic steatosis. Diet or bariatric surgery can reduce liver volume, fat content, and inflammation. However, little is known about their effects on liver function, as evaluated here using the LiMAx test.
View Article and Find Full Text PDFJ Racial Ethn Health Disparities
January 2025
Jefferson Collaborative for Health Equity, Jefferson Health, Philadelphia, PA, USA.
Background: Lack of access to reliable transportation is a barrier to utilizing healthcare and other resources related to type 2 diabetes mellitus (T2DM). Little research has evaluated race/ethnicity-based differences in access to reliable transportation among persons with T2DM.
Purpose: To examine whether access to reliable transportation for persons with T2DM differed by race/ethnicity.
Acta Diabetol
January 2025
Section for Clinical Oral Microbiology, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Nørre Allé 20, 2200, Copenhagen, Denmark.
Background: Evidence suggests a bidirectional relationship between oral health status and type 2 diabetes (T2D) in adults. Studies on associations between childhood oral health and T2D in adulthood are lacking.
Methods: This is a nationwide Danish registry-based cohort study of individuals born between 1963 and 1972, having at least one registration in the National Child Odontology Registry between 1972 and 1987 (n = 627,758).
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