Glucose transporters in cardiovascular system in health and disease

Bertrand, Luc; Auquier, Julien; Renguet, Edith; Angé, Marine; Cumps, Julien; Horman, Sandrine; Beauloye, Christophe

doi:10.1007/s00424-020-02444-8

Cited by 46 publications

(34 citation statements)

References 170 publications

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“…A recent study showed that the dual SGLT1/2 inhibitors may protect patients with diabetes from MI and stroke better, while the beneficial effects in patients without diabetes require more evaluation (Pitt and Bhatt, 2021). SGLT2 is the main cotransporter in humans that helps reabsorbing 80-90% of the glucose filtered by the glomerulus (Bonora et al, 2020), and SGLT1 helps reabsorbing additional renal glucose that evades SGLT2 (Bertrand et al, 2020). However, since the SGLT2i are available as therapeutic agents, most of the current clinical results reviewed are from SGLT2i.…”

Section: Sglt2 Inhibitors Can Increase the Production Of β-Ohbmentioning

confidence: 99%

Beta-Hydroxybutyrate, Friend or Foe for Stressed Hearts

2021

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One of the characteristics of the failing human heart is a significant alteration in its energy metabolism. Recently, a ketone body, β-hydroxybutyrate (β-OHB) has been implicated in the failing heart’s energy metabolism as an alternative “fuel source.” Utilization of β-OHB in the failing heart increases, and this serves as a “fuel switch” that has been demonstrated to become an adaptive response to stress during the heart failure progression in both diabetic and non-diabetic patients. In addition to serving as an alternative “fuel,” β-OHB represents a signaling molecule that acts as an endogenous histone deacetylase (HDAC) inhibitor. It can increase histone acetylation or lysine acetylation of other signaling molecules. β-OHB has been shown to decrease the production of reactive oxygen species and activate autophagy. Moreover, β-OHB works as an NLR family pyrin domain-containing protein 3 (Nlrp3) inflammasome inhibitor and reduces Nlrp3-mediated inflammatory responses. It has also been reported that β-OHB plays a role in transcriptional or post-translational regulations of various genes’ expression. Increasing β-OHB levels prior to ischemia/reperfusion injury results in a reduced infarct size in rodents, likely due to the signaling function of β-OHB in addition to its role in providing energy. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been shown to exert strong beneficial effects on the cardiovascular system. They are also capable of increasing the production of β-OHB, which may partially explain their clinical efficacy. Despite all of the beneficial effects of β-OHB, some studies have shown detrimental effects of long-term exposure to β-OHB. Furthermore, not all means of increasing β-OHB levels in the heart are equally effective in treating heart failure. The best timing and therapeutic strategies for the delivery of β-OHB to treat heart disease are unknown and yet to be determined. In this review, we focus on the crucial role of ketone bodies, particularly β-OHB, as both an energy source and a signaling molecule in the stressed heart and the overall therapeutic potential of this compound for cardiovascular diseases.

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Section: Sglt2 Inhibitors Can Increase the Production Of β-Ohbmentioning

confidence: 99%

Beta-Hydroxybutyrate, Friend or Foe for Stressed Hearts

2021

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“…While GLUT1 is regarded as the basal glucose transporter, GLUT4 is responsible for the increase in glucose uptake upon stimulation. Under basal conditions, GLUT4 is stored in transport vesicles and is actively transferred to membrane in response to insulin or increased workload [ 40 ]. Although GLUT1 is considered to be constitutively located at the plasma membrane, the presence of a cytoplasmic pool of GLUT1 has also been reported in cardiomyocytes [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…These cells have the ability to differentiate toward a cardiac phenotype and show energy metabolism patterns similar to primary cardiomyocyte [ 55 , 56 ]. However, a clear disadvantage of H9C2 cardiomyoblasts is that they are characterized by high GLUT1 expression and poor insulin responsiveness, rendering them more comparable to embryonic or neonatal cardiomyocytes than to adult cardiomyocytes [ 40 ]. Therefore, future experiments need to find better strategies to genetically manipulate the receptors.…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of CTRP-Mediated Effects on Cardiomyocyte Glucose Metabolism: Cross Talk between AMPK and Akt Signaling Pathway

Aslam

Siegler

et al. 2021

Cells

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C1q /tumor necrosis factor -alpha-related proteins (CTRPs) have been shown to mediate protective cardiovascular effects, but no data exists on their effects on glucose and fatty acid (FA) metabolism in cardiomyocytes. In the present study, adult rat cardiomyocytes and H9C2 cardiomyoblasts were stimulated with various recombinant CTRPs. Glucose or FA uptake, expression of genes involved in glucose or FA metabolism and the role of the AMP-activated protein kinase (AMPK) and Akt were investigated. Although most CTRPs induced an increase in phosphorylation of AMPK and Akt in cardiomyocytes, mainly CTRP2, 7, 9 and 13 induced GLUT1 and GLUT4 translocation and glucose uptake in cardiomyocytes, despite high structural similarities among CTRPs. AMPK inhibition reduced the CTRPs-mediated activation of Akt, while Akt inhibition did not impair AMPK activation. In addition, CTRP2, 7, 9 and 13 mediated strong effects on the expression of enzymes involved in glucose or FA metabolism. Loss of adiponectin receptor 1, which has been suggested to be involved in CTRP-induced signal transduction, abolished the effects of some but not all CTRPs on glucose metabolism. Targeting the AMPK signaling pathway via CTRPs may offer a therapeutic principle to restore glucose homeostasis by acting on glucose uptake independent of the Akt pathway.

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“…SGLTs are a family of glucose transporters encoded by SLC5 . To date, seven SGLTs have been identified [ 25 , 26 ], among which SGLT1 and SGLT2 are the major isoforms investigated. SGLT1 is abundant in the small intestine and expressed in the kidney, whereas SGLT2 is exclusively expressed in the kidneys [ 25 ].…”

Section: Mechanisms Underlying the Renoprotective Effect Of Sglt2 Inhibitorsmentioning

confidence: 99%

Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors: Renoprotective Mechanisms beyond Glycemic Control

Takata

Isomoto

2021

IJMS

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Diabetes mellitus is a major cause of chronic kidney disease and end-stage renal disease. However, the management of chronic kidney disease, particularly diabetes, requires vast improvements. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for the treatment of diabetes, have been shown to protect against kidney injury via glycemic control, as well as various other mechanisms, including blood pressure and hemodynamic regulation, protection from lipotoxicity, and uric acid control. As such, regulation of these mechanisms is recommended as an effective multidisciplinary approach for the treatment of diabetic patients with kidney disease. Thus, SGLT2 inhibitors are expected to become key drugs for treating diabetic kidney disease. This review summarizes the recent clinical evidence pertaining to SGLT2 inhibitors as well as the mechanisms underlying their renoprotective effects. Hence, the information contained herein will advance the current understanding regarding the pleiotropic effects of SGLT2 inhibitors, while promoting future research in the field.

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Glucose transporters in cardiovascular system in health and disease

Cited by 46 publications

References 170 publications

Beta-Hydroxybutyrate, Friend or Foe for Stressed Hearts

Beta-Hydroxybutyrate, Friend or Foe for Stressed Hearts

Comparative Analysis of CTRP-Mediated Effects on Cardiomyocyte Glucose Metabolism: Cross Talk between AMPK and Akt Signaling Pathway

Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors: Renoprotective Mechanisms beyond Glycemic Control

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