Inhibition of RIPK1 kinase does not affect diabetes development: β-Cells survive RIPK1 activation

Takiishi, Tatiana; Xiao, Peng; Franchimont, Marie; Gilglioni, Eduardo Hideo; Arroba, Erick N.; Gurzov, Esteban Nicolas; Bertrand, Mathieu; Cardozo, Alessandra K

doi:10.1016/j.molmet.2023.101681

Cited by 4 publications

(6 citation statements)

References 39 publications

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“…Our study is in line with the latter and with Takiishi et al. who showed that RIPK1-mediated cell death does not play a role in type 1 diabetes by using Ripk1 S25D mice under the same type 1 diabetes challenge [ 18 ]. In addition, Karunakaran et al.…”

Section: Discussionsupporting

confidence: 92%

“…Pancreatic islets were separated using density gradient (Histopaque-1077; Sigma Aldrich), followed by handpicking under microscope. Islets were cultured as described in [ 18 ]. The concentration of cytokines in the cocktail was used as follows: mTNF, 1000 U/mL (410-MT-025, R&D Systems), mIFN-γ, 1000 U/mL (315-05-100ug, Peprotech) and hIL-1β, 50 U/mL (201-LB-005, R&D Systems).…”

Section: Methodsmentioning

confidence: 99%

“…Cell death levels in islets were assessed by two independent researchers and one of the researchers was not aware of the treatment conditions as performed in Takiishi et al. [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…In particular, the respective contribution of death receptor-induced apoptosis and necroptosis as well as the implication of RIPK1 function in type 1 diabetes are unclear. Gene variants of RIPK1 are associated with metabolic syndrome in humans, and RIPK1 depletion, but not the inhibition of its kinase activity, was shown to protect from metabolic syndrome in mice [ 17 , 18 ]. On the contrary, Necrostatin-1s, a RIPK1 kinase inhibitor, was shown to protect from metabolic syndrome [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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RIPK1 is dispensable for cell death regulation in β-cells during hyperglycemia

Veli,

Kaya,

Varanda

et al. 2024

Molecular Metabolism

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

“…Cell death levels in islets were assessed by two independent researchers and one of the researchers was not aware of the treatment conditions as performed in Takiishi et al. [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

RIPK1 is dispensable for cell death regulation in β-cells during hyperglycemia

Veli,

Kaya,

Varanda

et al. 2024

Molecular Metabolism

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“…Another recent study demonstrated that genetic inhibition of RIP1 kinase activity ( Rip1 K45D/K45D ) reduced hepatic cell death and inflammation, alleviating hepatic steatosis, liver damage, and fibrosis in both methionine-choline deficient (MCD) and HFD dietary models (Tao et al, 2021 ). Surprisingly, both kinase-dead Rip1 K45D/K45D and Rip1 S25D/S25D had minimal effect on glucose metabolism and β-cell function in immune-mediated diabetes and diet-induced obesity (DIO) (Takiishi et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Mediators of necroptosis: from cell death to metabolic regulation

Wu,

Nagy,

Gautheron

2024

EMBO Mol Med

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Necroptosis, a programmed cell death mechanism distinct from apoptosis, has garnered attention for its role in various pathological conditions. While initially recognized for its involvement in cell death, recent research has revealed that key necroptotic mediators, including receptor-interacting protein kinases (RIPKs) and mixed lineage kinase domain-like protein (MLKL), possess additional functions that go beyond inducing cell demise. These functions encompass influencing critical aspects of metabolic regulation, such as energy metabolism, glucose homeostasis, and lipid metabolism. Dysregulated necroptosis has been implicated in metabolic diseases, including obesity, diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD), contributing to chronic inflammation and tissue damage. This review provides insight into the multifaceted role of necroptosis, encompassing both cell death and these extra-necroptotic functions, in the context of metabolic diseases. Understanding this intricate interplay is crucial for developing targeted therapeutic strategies in diseases that currently lack effective treatments.

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