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García-Arias, Mario R.; Gonzaga-López, Teresa Ivonne; González-Fernández, Nadia del Carmen; Guzmán-Ramírez, Perla Marlene; Ángeles-Acuña, Abish; Enríquez-Peregrino, Kevin Giuseppe; León, Juan Carlos Hintze-de; Marín-Reyes, Aldo Hernán; Cedillo-Rivera, Eliu Alejandro

doi:10.24245/mim.v34i6.2140

Cited by 1 publication

(3 citation statements)

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“…Reabsorbed glucose is then released into the circulatory system through facilitated diffusion thanks to glucose transporters type 1 and 2 (specifically GLUT1 and GLUT2, respectively), as illustrated in Figure 1 , which are located in the epithelial cells, but in the direction of the basolateral membrane [ 5 ]. When the amount of serum glucose exceeds 180–200 mg/dL (11.11 mmol/L)—thus surpassing the reabsorption capacity of the kidney—glycosuria occurs as a result, which is also an occurrence that is observed in patients with uncontrolled T2DM [ 3 , 4 , 7 ].…”

Section: Function Of Glucose Transporters and Sodium–glucose Cotransp...mentioning

confidence: 99%

“…Considering the fact that—in HF—there is an increased circulating volume load, with inadequate arterial perfusion due to impaired cardiac function, interstitial volume reduction may be more favorable for HF patients. For that reason, it is likely that natriuresis and a reduced volume load will explain, in part, the protective effects of SGLT2i in HF [ 5 ].…”

Section: Hemodynamic Mechanisms Of Sglt2 Inhibitorsmentioning

confidence: 99%

“…It is also believed that the ketogenic properties of SGLT2i could explain their antihypertensive effects, independent of renal function. Therefore, it is likely that natriuresis and the reduced volume load explain, in part, the protective effects of SGLT2i with respect to heart failure (HF) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Renal and Cardiovascular Metabolic Impact Caused by Ketogenesis of the SGLT2 Inhibitors

Vargas-Delgado

Herrera

Mite

et al. 2023

IJMS

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Sodium–glucose cotransporter type 2 inhibitors (SGLT2i) are glycosuric drugs that were originally developed for the treatment of type 2 diabetes mellitus (T2DM). There is a hypothesis that SGLT2i are drugs that are capable of increasing ketone bodies and free fatty acids. The idea is that they could serve as the necessary fuel, instead of glucose, for the purposes of cardiac muscle requirements and could explain antihypertensive effects, which are independent of renal function. The adult heart, under normal conditions, consumes around 60% to 90% of the cardiac energy that is derived from the oxidation of free fatty acids. In addition, a small proportion also comes from other available substrates. In order to meet energy demands with respect to achieving adequate cardiac function, the heart is known to possess metabolic flexibility. This allows it to switch between different available substrates in order to obtain the energy molecule adenosine triphosphate (ATP), thereby rendering it highly adaptive. It must be noted that oxidative phosphorylation in aerobic organisms is the main source of ATP, which is a result of reduced cofactors. These cofactors include nicotine adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2), which are the result of electron transfer and are used as the enzymatic cofactors that are involved in the respiratory chain. When there is an excessive increase in energy nutrients—such as glucose and fatty acids—which occur in the absence of a parallel increase in demand, a state of nutrient surplus (which is better known as an excess in supply) is created. The use of SGLT2i at the renal level has also been shown to generate beneficial metabolic alterations, which are obtained by reducing the glucotoxicity that is induced by glycosuria. Together with the reduction in perivisceral fat in various organs, such alterations also lead to the use of free fatty acids in the initial stages of the affected heart. Subsequently, this results in an increase in production with respect to ketoacids, which are a more available energy fuel at the cellular level. In addition, even though their mechanism is not fully understood, their vast benefits render them of incredible importance for the purposes of further research.

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Section: Function Of Glucose Transporters and Sodium–glucose Cotransp...mentioning

confidence: 99%

Section: Hemodynamic Mechanisms Of Sglt2 Inhibitorsmentioning

confidence: 99%