Spotlight on the Human Brain: Central Actions of SGLT2 Inhibitors?

Hummel, Julia Richter; Kullmann, Stephanie; Heni, Martin

doi:10.1210/clinem/dgac179

Cited by 4 publications

(1 citation statement)

References 8 publications

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“…In line with these findings, brain effects have been reported for dapagliflozin, another SGLT2 inhibitor [ 97 ]. While this study was focused on food-cue reactivity and did not test brain insulin responsiveness, it appears likely that empagliflozin and dapagliflozin have comparable effects [ 98 ]. While SGLT2 is expressed in the brain [ 99 ], it is unclear whether these pharmacological inhibitors act there directly or indirectly via peripheral action with subsequent projections towards the brain [ 98 , 99 ].…”

Section: Treatment Of Brain Insulin Resistancementioning

confidence: 99%

The insulin resistant brain: impact on whole-body metabolism and body fat distribution

Heni

2024

Diabetologia

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Insulin exerts its actions not only on peripheral organs but is also transported into the brain where it performs distinct functions in various brain regions. This review highlights recent advancements in our understanding of insulin’s actions within the brain, with a specific emphasis on investigations in humans. It summarises current knowledge on the transport of insulin into the brain. Subsequently, it showcases robust evidence demonstrating the existence and physiological consequences of brain insulin action, while also introducing the presence of brain insulin resistance in humans. This pathophysiological condition goes along with an impaired acute modulation of peripheral metabolism in response to brain insulin action, particularly in the postprandial state. Furthermore, brain insulin resistance has been associated with long-term adiposity and an unfavourable adipose tissue distribution, thus implicating it in the pathogenesis of subgroups of obesity and (pre)diabetes that are characterised by distinct patterns of body fat distribution. Encouragingly, emerging evidence suggests that brain insulin resistance could represent a treatable entity, thereby opening up novel therapeutic avenues to improve systemic metabolism and enhance brain functions, including cognition. The review closes with an outlook towards prospective research directions aimed at further elucidating the clinical implications of brain insulin resistance. It emphasises the critical need to establish feasible diagnostic measures and effective therapeutic interventions. Graphical Abstract

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Section: Treatment Of Brain Insulin Resistancementioning

confidence: 99%

The insulin resistant brain: impact on whole-body metabolism and body fat distribution

Heni

2024

Diabetologia

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Molecular and neural roles of sodium-glucose cotransporter 2 inhibitors in alleviating neurocognitive impairment in diabetic mice

et al. 2023

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Diabetes causes a variety of molecular changes in the brain, making it a real risk factor for the development of cognitive dysfunction. Complex pathogenesis and clinical heterogeneity of cognitive impairment makes the efficacy of current drugs limited. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) gained our attention as drugs with potential beneficial effects on the CNS. In the present study, these drugs ameliorated the cognitive impairment associated with diabetes. Moreover, we verified whether SGLT2i can mediate the degradation of amyloid precursor protein (APP) and modulation of gene expression (Bdnf, Snca, App) involved in the control of neuronal proliferation and memory. The results of our research proved the participation of SGLT2i in the multifactorial process of neuroprotection. SGLT2i attenuate the neurocognitive impairment through the restoration of neurotrophin levels, modulation of neuroinflammatory signaling, and gene expression of Snca, Bdnf, and App in the brain of diabetic mice. The targeting of the above-mentioned genes is currently seen as one of the most promising and developed therapeutic strategies for diseases associated with cognitive dysfunction. The results of this work could form the basis of a future administration of SGLT2i in diabetics with neurocognitive impairment.

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The brain as a central regulator of metabolism

Hummel,

Heni

2024

Diabetologie

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Spotlight on the Human Brain: Central Actions of SGLT2 Inhibitors?

Cited by 4 publications

References 8 publications

The insulin resistant brain: impact on whole-body metabolism and body fat distribution

The insulin resistant brain: impact on whole-body metabolism and body fat distribution

Molecular and neural roles of sodium-glucose cotransporter 2 inhibitors in alleviating neurocognitive impairment in diabetic mice

The brain as a central regulator of metabolism

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