Emerging links between FOXOs and diabetic complications

Parmar, Urvi M.; Jalgaonkar, Manjiri P.; Kansara, Aayush J.; Oza, Manisha J.

doi:10.1016/j.ejphar.2023.176089

Cited by 7 publications

(1 citation statement)

References 61 publications

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“…Foxo1 has been validated to be essential for sustaining the quiescence of endothelial cells, with involvement in metabolism regulation [34, 40]. Moreover, it also plays important roles in diabetic microvascular complications including DR[41, 42]. Here, by combining the single-cell transcriptomic sequencing data analysis and experimental validation, we identified the transcription factor Foxo1a, which was significantly down-regulated in the embryos treated with high glucose, responsible for the excessive angiogenesis.…”

Section: Discussionmentioning

confidence: 95%

Noncaloric monosaccharides induce excessive sprouting angiogenesis in zebrafish via foxo1a-marcksl1a signal

Wang,

Zhao,

et al. 2024

Preprint

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Artificially sweetened beverages containing noncaloric monosaccharides were suggested as healthier alternatives to sugar-sweetened beverages. Nevertheless, the potential detrimental effects of these noncaloric monosaccharides on blood vessel function remain inadequately understood. Presently, we have established a zebrafish model that exhibits significant excessive angiogenesis induced by high glucose, resembling the hyperangiogenic characteristics observed in proliferative diabetic retinopathy (PDR). Utilizing this model, we observed that glucose and noncaloric monosaccharides could induce excessive formation of blood vessels, especially intersegmental vessels (ISVs). The excessively branched vessels were observed to be formed by ectopic activation of quiescent endothelial cells (ECs) into tip cells. Single-cell transcriptomic sequencing analysis of the endothelial cells in the embryos exposed to high glucose revealed an augmented ratio of capillary ECs, proliferating ECs, and a series of upregulated proangiogenic genes. Further analysis and experiments validated that foxo1a mediated the excessive angiogenesis induced by monosaccharides by down-regulating the expression ofmarcksl1a. This study has provided new evidence showing the negative effects of noncaloric monosaccharides on the vascular system and the underlying mechanisms.

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Section: Discussionmentioning

confidence: 95%

Noncaloric monosaccharides induce excessive sprouting angiogenesis in zebrafish via foxo1a-marcksl1a signal

Wang,

Zhao,

et al. 2024

Preprint

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Network pharmacology, molecular docking and experimental validation to elucidate the anti-T2DM mechanism of Lanxangia tsaoko

Wang,

Li,

Chen

et al. 2024

Fitoterapia

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Cannabidiol and Beta-Caryophyllene Combination Attenuates Diabetic Neuropathy by Inhibiting NLRP3 Inflammasome/NFκB through the AMPK/sirT3/Nrf2 Axis

Khan,

Kaur,

Rishi

et al. 2024

Biomedicines

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Background: In this study, we investigated in detail the role of cannabidiol (CBD), beta-caryophyllene (BC), or their combinations in diabetic peripheral neuropathy (DN). The key factors that contribute to DN include mitochondrial dysfunction, inflammation, and oxidative stress. Methods: Briefly, streptozotocin (STZ) (55 mg/kg) was injected intraperitoneally to induce DN in Sprague–Dawley rats, and we performed procedures involving Randall Sellito calipers, a Von Frey aesthesiometer, a hot plate, and cold plate methods to determine mechanical and thermal hyperalgesia in vivo. The blood flow to the nerves was assessed using a laser Doppler device. Schwann cells were exposed to high glucose (HG) at a dose of 30 mM to induce hyperglycemia and DCFDA, and JC1 and Mitosox staining were performed to determine mitochondrial membrane potential, reactive oxygen species, and mitochondrial superoxides in vitro. The rats were administered BC (30 mg/kg), CBD (15 mg/kg), or combination via i.p. injections, while Schwann cells were treated with 3.65 µM CBD, 75 µM BC, or combination to assess their role in DN amelioration. Results: Our results revealed that exposure to BC and CBD diminished HG-induced hyperglycemia in Schwann cells, in part by reducing mitochondrial membrane potential, reactive oxygen species, and mitochondrial superoxides. Furthermore, the BC and CBD combination treatment in vivo could prevent the deterioration of the mitochondrial quality control system by promoting autophagy and mitochondrial biogenesis while improving blood flow. CBD and BC treatments also reduced pain hypersensitivity to hyperalgesia and allodynia, with increased antioxidant and anti-inflammatory action in diabetic rats. These in vivo effects were attributed to significant upregulation of AMPK, sirT3, Nrf2, PINK1, PARKIN, LC3B, Beclin1, and TFAM functions, while downregulation of NLRP3 inflammasome, NFκB, COX2, and p62 activity was noted using Western blotting. Conclusions: the present study demonstrated that STZ and HG-induced oxidative and nitrosative stress play a crucial role in the pathogenesis of diabetic neuropathy. We find, for the first time, that a CBD and BC combination ameliorates DN by modulating the mitochondrial quality control system.

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Emerging links between FOXOs and diabetic complications

Cited by 7 publications

References 61 publications

Noncaloric monosaccharides induce excessive sprouting angiogenesis in zebrafish via foxo1a-marcksl1a signal

Noncaloric monosaccharides induce excessive sprouting angiogenesis in zebrafish via foxo1a-marcksl1a signal

Network pharmacology, molecular docking and experimental validation to elucidate the anti-T2DM mechanism of Lanxangia tsaoko

Cannabidiol and Beta-Caryophyllene Combination Attenuates Diabetic Neuropathy by Inhibiting NLRP3 Inflammasome/NFκB through the AMPK/sirT3/Nrf2 Axis

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