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Neuronal Dysfunctio...
Neuronal Dysfunction Is Linked to the Famine-Associated Risk of Proliferative Retinopathy in Patients With Type 2 Diabetes
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- Fedotkina, Olena (författare)
- University of Bergen
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- Jain, Ruchi (författare)
- Lund University,Lunds universitet,Öcellsfysiologi,Forskargrupper vid Lunds universitet,Islet cell physiology,Lund University Research Groups,Skåne University Hospital,Skåne University Hospital: Memory Clinic (MemoryHealth)
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- Prasad, Rashmi B (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Luk, Andrea (författare)
- Chinese University of Hong Kong
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- García-Ramírez, Marta (författare)
- CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
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- Özgümüs, Türküler (författare)
- University of Bergen
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- Cherviakova, Liubov (författare)
- Chernigov Chernihiv Regional Oncology Hospital
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- Khalimon, Nadiya (författare)
- City Hospital, Chernihiv
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- Svietleisha, Tetiana (författare)
- City Hospital, Chernihiv
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- Buldenko, Tetiana (författare)
- Chernihiv Regional State Administration
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- Kravchenko, Victor (författare)
- V. P. Komisarenko Institute of Endocrinology and Metabolism of the Ukraine Academy of Medical Sciences
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- Jain, Deepak (författare)
- Lund University,Lunds universitet,Skåne University Hospital
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- Vaag, Allan (författare)
- Steno Diabetes Center Copenhagen
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- Chan, Juliana (författare)
- Chinese University of Hong Kong
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- Khalangot, Mykola D (författare)
- V. P. Komisarenko Institute of Endocrinology and Metabolism of the Ukraine Academy of Medical Sciences,Shupyk National Healthcare University of Ukraine
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- Hernández, Cristina (författare)
- CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
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- Nilsson, Peter M (författare)
- Lund University,Lunds universitet,Enheten för medicinens historia,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,History of Medicine,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Internal Medicine - Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Simo, Rafael (författare)
- CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
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- Artner, Isabella (författare)
- Lund University,Lunds universitet,Endokrin Celldifferentiering,Forskargrupper vid Lunds universitet,Endocrine Cell Differentiation and Function,Lund University Research Groups,Skåne University Hospital
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- Lyssenko, Valeriya (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital,University of Bergen
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(creator_code:org_t)
- 2022-05-05
- 2022
- Engelska.
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 16, s. 858049-858049
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Persons with type 2 diabetes born in the regions of famine exposures have disproportionally elevated risk of vision-threatening proliferative diabetic retinopathy (PDR) in adulthood. However, the underlying mechanisms are not known. In the present study, we aimed to investigate the plausible molecular factors underlying progression to PDR. To study the association of genetic variants with PDR under the intrauterine famine exposure, we analyzed single nucleotide polymorphisms (SNPs) that were previously reported to be associated with type 2 diabetes, glucose, and pharmacogenetics. Analyses were performed in the population from northern Ukraine with a history of exposure to the Great Ukrainian Holodomor famine [the Diagnostic Optimization and Treatment of Diabetes and its Complications in the Chernihiv Region (DOLCE study), n = 3,583]. A validation of the top genetic findings was performed in the Hong Kong diabetes registry (HKDR, n = 730) with a history of famine as a consequence of the Japanese invasion during WWII. In DOLCE, the genetic risk for PDR was elevated for the variants in ADRA2A, PCSK9, and CYP2C19*2 loci, but reduced at PROX1 locus. The association of ADRA2A loci with the risk of advanced diabetic retinopathy in famine-exposed group was further replicated in HKDR. The exposure of embryonic retinal cells to starvation for glucose, mimicking the perinatal exposure to famine, resulted in sustained increased expression of Adra2a and Pcsk9, but decreased Prox1. The exposure to starvation exhibited a lasting inhibitory effects on neurite outgrowth, as determined by neurite length. In conclusion, a consistent genetic findings on the famine-linked risk of ADRA2A with PDR indicate that the nerves may likely to be responsible for communicating the effects of perinatal exposure to famine on the elevated risk of advanced stages of diabetic retinopathy in adults. These results suggest the possibility of utilizing neuroprotective drugs for the prevention and treatment of PDR.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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Fedotkina, Olena
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Jain, Ruchi
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Prasad, Rashmi B
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Luk, Andrea
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García-Ramírez, ...
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Özgümüs, Türküle ...
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visa fler...
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Cherviakova, Liu ...
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Khalimon, Nadiya
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Svietleisha, Tet ...
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Buldenko, Tetian ...
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Kravchenko, Vict ...
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Jain, Deepak
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Vaag, Allan
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Chan, Juliana
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Khalangot, Mykol ...
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Hernández, Crist ...
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Nilsson, Peter M
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Simo, Rafael
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Artner, Isabella
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Lyssenko, Valeri ...
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