TW68, Cryptochromes stabilizer, regulates fasting blood glucose level inob/oband fat-induced diabetic mice Article Swipe
Saliha Sürme
,
Cagla Ergun Ayva
,
Şeref Gül
,
Yasemin Kübra Akyel
,
Zeynep Melis Gül
,
Onur Özcan
,
Özgecan Şavluğ İpek
,
Busra A. Akarlar
,
Nurhan Özlü
,
Ali Cihan Taşkın
,
Metin Türkay
,
Ahmet C. Gören
,
İbrahim Barış
,
Nuri Öztürk
,
Mustafa Güzel
,
Cihan Aydın
,
Alper Okyar
,
İbrahim Halil Kavaklı
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.07.13.548861
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.07.13.548861
Cryptochromes (CRYs), transcriptional repressors of the circadian clock in mammals, inhibit cAMP production when glucagon activates G-protein coupled receptors. Therefore, molecules that modulate CRYs have the potential to regulate gluconeogenesis. In this study, we discovered a new molecule called TW68 that interacts with the primary pockets of mammalian CRY1/2, leading to reduced ubiquitination levels and increased stability. In cell-based circadian rhythm assays using U2OS: Bmal1 -d Luc cells, TW68 extended the period length of the circadian rhythm. Additionally, TW68 decreased the transcriptional levels of two genes, Phosphoenolpyruvate carboxykinase 1 ( PCK1 ) and Glucose-6-phosphatase ( G6PC ), which play crucial roles in glucose biosynthesis during glucagon-induced gluconeogenesis in HepG2 cells. Oral administration of TW68 in mice showed good tolerance, a good pharmacokinetic profile, and remarkable bioavailability. Finally, when administered to fasting ob/ob and fat-induced diabetic animals, TW68 reduced blood glucose levels by enhancing CRY stabilization and subsequently decreasing the transcriptional levels of Pck1 and G6pc . These findings collectively demonstrate the antidiabetic efficacy of TW68 in vivo , suggesting its therapeutic potential for controlling fasting glucose levels in the treatment of type 2 diabetes mellitus .
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.07.13.548861
- https://www.biorxiv.org/content/biorxiv/early/2023/07/13/2023.07.13.548861.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 60
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4384341314
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4384341314Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2023.07.13.548861Digital Object Identifier
- Title
-
TW68, Cryptochromes stabilizer, regulates fasting blood glucose level inob/oband fat-induced diabetic miceWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-07-13Full publication date if available
- Authors
-
Saliha Sürme, Cagla Ergun Ayva, Şeref Gül, Yasemin Kübra Akyel, Zeynep Melis Gül, Onur Özcan, Özgecan Şavluğ İpek, Busra A. Akarlar, Nurhan Özlü, Ali Cihan Taşkın, Metin Türkay, Ahmet C. Gören, İbrahim Barış, Nuri Öztürk, Mustafa Güzel, Cihan Aydın, Alper Okyar, İbrahim Halil KavaklıList of authors in order
- Landing page
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https://doi.org/10.1101/2023.07.13.548861Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2023/07/13/2023.07.13.548861.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2023/07/13/2023.07.13.548861.full.pdfDirect OA link when available
- Concepts
-
Endocrinology, Internal medicine, Gluconeogenesis, Phosphoenolpyruvate carboxykinase, Circadian rhythm, Circadian clock, Cryptochrome, Hypoglycemia, Glucagon, Downregulation and upregulation, Biology, Receptor, Diabetes mellitus, Chemistry, Insulin, Medicine, Metabolism, Gene, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
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2023: 1Per-year citation counts (last 5 years)
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60Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.rhythm. | 77 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.Finally, | 127 |
| abstract_inverted_index.animals, | 136 |
| abstract_inverted_index.diabetes | 184 |
| abstract_inverted_index.diabetic | 135 |
| abstract_inverted_index.efficacy | 163 |
| abstract_inverted_index.extended | 70 |
| abstract_inverted_index.findings | 158 |
| abstract_inverted_index.glucagon | 15 |
| abstract_inverted_index.mammals, | 10 |
| abstract_inverted_index.mellitus | 185 |
| abstract_inverted_index.modulate | 23 |
| abstract_inverted_index.molecule | 38 |
| abstract_inverted_index.profile, | 123 |
| abstract_inverted_index.regulate | 29 |
| abstract_inverted_index.G-protein | 17 |
| abstract_inverted_index.activates | 16 |
| abstract_inverted_index.circadian | 7, 60, 76 |
| abstract_inverted_index.decreased | 80 |
| abstract_inverted_index.enhancing | 143 |
| abstract_inverted_index.increased | 56 |
| abstract_inverted_index.interacts | 42 |
| abstract_inverted_index.mammalian | 48 |
| abstract_inverted_index.molecules | 21 |
| abstract_inverted_index.potential | 27, 172 |
| abstract_inverted_index.treatment | 180 |
| abstract_inverted_index.Therefore, | 20 |
| abstract_inverted_index.cell-based | 59 |
| abstract_inverted_index.decreasing | 148 |
| abstract_inverted_index.discovered | 35 |
| abstract_inverted_index.production | 13 |
| abstract_inverted_index.receptors. | 19 |
| abstract_inverted_index.remarkable | 125 |
| abstract_inverted_index.repressors | 4 |
| abstract_inverted_index.stability. | 57 |
| abstract_inverted_index.suggesting | 169 |
| abstract_inverted_index.tolerance, | 119 |
| abstract_inverted_index.controlling | 174 |
| abstract_inverted_index.demonstrate | 160 |
| abstract_inverted_index.fat-induced | 134 |
| abstract_inverted_index.therapeutic | 171 |
| abstract_inverted_index.administered | 129 |
| abstract_inverted_index.antidiabetic | 162 |
| abstract_inverted_index.biosynthesis | 104 |
| abstract_inverted_index.collectively | 159 |
| abstract_inverted_index.subsequently | 147 |
| abstract_inverted_index.Additionally, | 78 |
| abstract_inverted_index.Cryptochromes | 1 |
| abstract_inverted_index.carboxykinase | 88 |
| abstract_inverted_index.stabilization | 145 |
| abstract_inverted_index.administration | 112 |
| abstract_inverted_index.ubiquitination | 53 |
| abstract_inverted_index.gluconeogenesis | 107 |
| abstract_inverted_index.pharmacokinetic | 122 |
| abstract_inverted_index.transcriptional | 3, 82, 150 |
| abstract_inverted_index.bioavailability. | 126 |
| abstract_inverted_index.glucagon-induced | 106 |
| abstract_inverted_index.gluconeogenesis. | 30 |
| abstract_inverted_index.Phosphoenolpyruvate | 87 |
| abstract_inverted_index.Glucose-6-phosphatase | 94 |
| cited_by_percentile_year.max | 94 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5063155558 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 18 |
| corresponding_institution_ids | https://openalex.org/I1351752 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7400000095367432 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.47953114 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |