Small vesicles called exosomes have been found to regulate gene expression in tissues and play a role in the pathogenesis of many diseases. Therefore, this study aimed to determine the effects of exosomes on diabetes and related microRNA (miRNA) exchange. For this purpose, nicotinamide (120 mg/kg) was administered intraperitoneally (IP.), and Streptozotocin (50 mg/kg) ip was allocated 15 minutes later. Rats with 126 mg/dL and up glucose levels were accepted as Type 2 diabetes. At the end of 21 days, exosomes were obtained from the pancreas and brain tissues of rats (n:10) of diabetics and healthy groups. Then biochemical analyzes and oxidative stress parameters of both groups were examined. In addition, miRNA changes were discussed, and the results obtained were statistically evaluated. A significant increase was found in total oxidative status (TOS) and Lactate dehydrogenase (LDH) levels in both brain and pancreatic exosomes. It was observed that the total antioxidant level (TAC) decreased compared to the control group (P<0.05). As a result of the examination with Real-Time PCR, it was determined that the levels of miRNA -9 increased significantly in both brain tissue and pancreas tissue, and miR-146 gene levels were down-regulated considerably (P<0.05).
As a result, significant changes occurred in miRNA -9 and -146 levels in the brain and pancreatic tissue exosomes of diabetic rats. The results suggest that exosomes may have a role in miRNAs mediating neuroinflammation in the brain and pancreatic tissue.
Ashrafizadeh, M., Kumar, A.P., Aref, A.R., Zarrabi, A. &
Mostafavi, E. (2022). Exosomes as promising
nanostructures in diabetes mellitus: from insulin
sensitivity to ameliorating diabetic complications.
Int J Nanomedicine, 1229-1253.
Balasubramanyam, M., Aravind, S., Gokulakrishnan, K.,
Prabu, P., Sathishkumar, C., Ranjani, H. &
Mohan, V. (2011). Impaired miR-146a expression
links subclinical inflammation and insulin resistance
in Type 2 diabetes. Molecular and cellular
biochemistry, 351, 197-205.
Baldeón, R.L., Weigelt, K., De Wit, H., Ozcan, B., van
Oudenaren, A., Sempertegui, F., Sijbrands, E.,
Grosse, L., Freire, W. & Drexhage, H.A. (2014).
Decreased serum level of miR-146a as sign of
chronic inflammation in type 2 diabetic patients.
PLoS One, 9(12), e115209.
Bazzoni, F., Rossato, M., Fabbri, M., Gaudiosi, D., Mirolo,
M., Mori, L., Tamassia, N., Mantovani, A.,
Cassatella, M.A., & Locati, M. (2009). Induction
and regulatory function of miR-9 in human
monocytes and neutrophils exposed to
proinflammatory signals. Proceedings of the
National Academy of Sciences, 106(13), 5282-5287.
Biessels, G. J. & Reagan, L. P. (2015). Hippocampal insulin
resistance and cognitive dysfunction. Nature
Reviews Neuroscience, 16(11), 660-671.
Brownlee, M. (2005). The pathobiology of diabetic
complications: a unifying mechanism. Diabetes,
54(6), 1615-1625.
Butler, A.E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza,
R.A. & Butler, P.C. (2003). β-cell deficit and
increased β-cell apoptosis in humans with type 2
diabetes. Diabetes, 52(1), 102-110.
Chatterjee, S., Khunti, K. & Davies, M.J. (2017). Type 2
diabetes. The lancet, 389(10085), 2239-2251.
Chen, W., Lou, J., Evans, E.A. & Zhu, C. (2012). Observing
force-regulated conformational changes and ligand
dissociation from a single integrin on cells. Journal
of Cell Biology, 199(3), 497-512.
Collaboration, N.R.F. (2017). Trends in obesity and diabetes
across Africa from 1980 to 2014: an analysis of
pooled population-based studies. International
journal of epidemiology, 46(5), 1421-1432.
Finnegan, E. J. & Matzke, M. A. (2003). The small RNA
world. Journal of cell science, 116(23), 4689-4693.
Ganesh Yerra, V., Negi, G., Sharma, S. & Kumar, A.
(2013). Potential therapeutic effects of the
simultaneous targeting of the Nrf2 and NF-κB
pathways in diabetic neuropathy. Redox Biol 1: 394-
397. In.
Genc, S., Yagci, T., Vageli, D. P., Dundar, R., Doukas, P.
G., Doukas, S. G., Tolia, M., Chatzakis, N.,
Tsatsakis, A. & Taghizadehghalehjoughi, A.
(2023). Exosomal MicroRNA-223, MicroRNA-146,
and MicroRNA-21 Profiles and Biochemical
Changes in Laryngeal Cancer. ACS Pharmacology
& Translational Science, 6(5), 820-828.
Gilbert, R.E. & Cooper, M.E. (1999). The tubulointerstitium
in progressive diabetic kidney disease: more than an
aftermath of glomerular injury? Kidney
international, 56(5), 1627-1637.
Guo, H.-Y., Cheng, A.-C., Wang, M.-S., Yin, Z.-Q. & Jia,
R.-Y. (2020). Exosomes: potential therapies for
disease via regulating TLRs. Mediators of
Inflammation, 2020.
Haligur, M., Topsakal, S. & Ozmen, O. (2012). Early
degenerative effects of diabetes mellitus on
pancreas, liver, and kidney in rats: an
immunohistochemical study. Journal of diabetes
research, 2012.
Impey, S., McCorkle, S.R., Cha-Molstad, H., Dwyer, J.M.,
Yochum, G.S., Boss, J.M., McWeeney, S., Dunn,
J.J., Mandel, G. & Goodman, R.H. (2004).
Defining the CREB regulon: a genome-wide
analysis of transcription factor regulatory regions.
Cell, 119(7), 1041-1054.
Kaplan, A., Cetin, M., Orgul, D., Hacimufnewlu, A., &
Hekimoglu, S. (2019). Formulation and In Vitro
Evaluation of Topical Nanoemulsion based Gels
Containing Daidzein. Journal of Drug Delivery
Science and Technology, 19, 30263.
Kluiver, J., van den Berg, A., de Jong, D., Blokzijl, T.,
Harms, G., Bouwman, E., Jacobs, S., Poppema, S.
& Kroesen, B.-J. (2007). Regulation of primicroRNA BIC transcription and processing in
Burkitt lymphoma. Oncogene, 26(26), 3769-3776.
Kodl, C. T., & Seaquist, E. R. (2008). Cognitive dysfunction
and diabetes mellitus. Endocrine reviews, 29(4),
494-511.
Kong, L., Zhu, J., Han, W., Jiang, X., Xu, M., Zhao, Y.,
Dong, Q., Pang, Z., Guan, Q. & Gao, L. (2011).
Significance of serum microRNAs in pre-diabetes
and newly diagnosed type 2 diabetes: a clinical
study. Acta diabetologica, 48, 61-69.
L Isola, A. & Chen, S. (2017). Exosomes: the messengers of
health and disease. Current neuropharmacology,
15(1), 157-165.
Li, Q., Zemel, E., Miller, B. & Perlman, I. (2002). Early
retinal damage in experimental diabetes:
electroretinographical and morphological
observations. Experimental eye research, 74(5),
615-625.
Lopes, M.B., Freitas, R.C., Hirata, M.H., Hirata, R.D.,
Rezende, A.A., Silbiger, V.N., Bortolin, R.H. &
Luchessi, A.D. (2017). mRNA-miRNA integrative
analysis of diabetes-induced cardiomyopathy in rats.
Frontiers in Bioscience-Scholar, 9(2), 194-229.
Masiello, P., Broca, C., Gross, R., Roye, M., Manteghetti,
M., Hillaire-Buys, D., Novelli, M., & Ribes, G.
(1998). Experimental NIDDM: development of a
new model in adult rats administered streptozotocin
and nicotinamide. Diabetes, 47(2), 224-229.
Mijnhout, G., Scheltens, P., Diamant, M., Biessels, G.,
Wessels, A., Simsek, S., Snoek, F., & Heine, R.
(2006). Diabetic encephalopathy: a concept in need
of a definition. Diabetologia, 49, 1447-1448.
Muriach, M., Flores-Bellver, M., Romero, F.J. & Barcia,
J.M. (2014). Diabetes and the brain: oxidative stress,
inflammation, and autophagy. Oxidative medicine
and cellular longevity, 2014.
Patel, S. & Santani, D. (2009). Role of NF-κB in the
pathogenesis of diabetes and its associated
complications. Pharmacological Reports, 61(4),
595-603.
Reed, M., Meszaros, K., Entes, L., Claypool, M., Pinkett,
J., Gadbois, T. & Reaven, G. (2000). A new rat
model of type 2 diabetes: the fat-fed, streptozotocintreated rat. Metabolism-Clinical and Experimental,
49(11), 1390-1394.
Sakshi, S., Jayasuriya, R., Ganesan, K., Xu, B. &
Ramkumar, K. M. (2021). Role of circRNAmiRNA-mRNA interaction network in diabetes and
its associated complications. Molecular TherapyNucleic Acids, 26, 1291-1302.
Samanta, S., Rajasingh, S., Drosos, N., Zhou, Z., Dawn, B.
& Rajasingh, J. (2018). Exosomes: new molecular
targets of diseases. Acta Pharmacol Sin, 39(4), 501-
513.
Shawky, L.M., Morsi, A.A., El Bana, E. & Hanafy, S. M.
(2019). The biological impacts of sitagliptin on the
pancreas of a rat model of type 2 diabetes mellitus:
Drug interactions with metformin. Biology, 9(1), 6.
Sıdıka, G., Cakir, Z., Taghizadehghalehjoughi, A., Yeşim,
Y., Jalili, K. & HACIMÜFTÜOĞLU, A. (2021).
Investigation of the Exosome-Based Drug Delivery
System Potential in theTreatment of Glioblastoma in
vitro Experimental Models. International Journal of
Life Sciences and Biotechnology, 4(3), 451-467.
Szkudelski, T. (2012). Streptozotocin–nicotinamide-induced
diabetes in the rat. Characteristics of the
experimental model. Experimental biology and
medicine, 237(5), 481-490.
Taganov, K.D., Boldin, M.P., Chang, K.-J. & Baltimore,
D. (2006). NF-κB-dependent induction of
microRNA miR-146, an inhibitor targeted to
signaling proteins of innate immune responses.
Proceedings of the National Academy of Sciences,
103(33), 12481-12486.
Targher, G., & Byrne, C. D. (2017). Non-alcoholic fatty
liver disease: an emerging driving force in chronic
kidney disease. Nature Reviews Nephrology, 13(5),
297-310.
Wang-Fischer, Y., & Garyantes, T. (2018). Improving the
reliability and utility of streptozotocin-induced rat
diabetic model. Journal of diabetes research, 2018.
Westermark, P., Wernstedt, C., Wilander, E., Hayden, D.
W., O'Brien, T. D. & Johnson, K. H. (1987).
Amyloid fibrils in human insulinoma and islets of
Langerhans of the diabetic cat are derived from a
neuropeptide-like protein also present in normal islet
cells. Proceedings of the National Academy of
Sciences, 84(11), 3881-3885.
Wong, C.H., Wanrooy, B.J. & Bruce, D.G. (2018).
Neuroinflammation, type 2 diabetes, and dementia.
In Type 2 Diabetes and Dementia (pp. 195-209).
Elsevier.
Wu, K.K. & Huan, Y. (2008). Streptozotocin‐induced
diabetic models in mice and rats. Current protocols
in pharmacology, 40(1), 5.47. 41-45.47. 14.
Ye, J., Zhu, J., Chen, H., Qian, J., Zhang, L., Wan, Z.,
Chen, F., Sun, S., Li, W. & Luo, C. (2020). A novel
lncRNA‐LINC01116 regulates tumorigenesis of
glioma by targeting VEGFA. Int J Cancer, 146(1),
248-261.
Yeni, Y., Taghizadehghalehjoughi, A., Genc, S.,
Hacimuftuoglu, A., Yildirim, S. & Bolat, I. (2023).
Glioblastoma cell-derived exosomes induce cell
death and oxidative stress in primary cultures of
olfactory neurons. Role of redox stress. Mol Biol
Rep, 50(5), 3999-4009.
Yeni, Y., Taghizadehghalehjoughi, A., Genc, S.,
Hacimuftuoglu, A., Yildirim, S. & Bolat, I. (2023).
Glioblastoma cell-derived exosomes induce cell
death and oxidative stress in primary cultures of
olfactory neurons. Role of redox stress. Mol Biol
Rep, 50(5), 3999-4009.
Zhang, N., He, F., Li, T., Chen, J., Jiang, L., Ouyang, X.-
P. & Zuo, L. (2021). Role of exosomes in brain
diseases. Front Cell Neurosci, 15, 743353.
Zhao, Y., Krishnamurthy, B., UA Mollah, Z., WH Kay, T.,
& E Thomas, H. (2011). NF-κB in type 1 diabetes.
Inflammation & Allergy-Drug Targets (Formerly
Current Drug Targets-Inflammation &
Allergy)(Discontinued), 10(3), 208-217.
Sağlıklı ve Diyabetli Sıçanlarda Beyin ve Pankreas Dokusundan İzole Edilen Eksozom -miRNA -9 ve -146 Profillerinin Karşılaştırılması
Eksozom adı verilen küçük veziküllerin dokulardaki gen ekspresyonunu düzenlediği ve birçok hastalığın patogenezinde rol oynadığı bulunmuştur. Bu nedenle, bu çalışma ekzozomların diyabet ve buna bağlı mikroRNA (miRNA) değişimi üzerindeki etkilerini belirlemeyi amaçlamıştır. Bu amaçla intraperitoneal olarak nikotinamid (120 mg/kg) uygulandı (ip.) ve 15 dakika sonra Streptozotosin (50 mg / kg) ip uygulandı. Glikoz seviyesi 126 mg/dL ve üzeri olan sıçanlar Tip 2 diyabet olarak kabul edildi. 21 Günün sonunda şeker hastalarının ve sağlıklı grupların sıçanlarının (n:10) pankreas ve beyin dokularından eksozomlar elde edildi. Daha sonra her iki grubun biyokimyasal analizleri ve oksidatif stres parametreleri incelendi. Ayrıca miRNA değişiklikleri incelenmiş ve elde edilen sonuçlar istatistiksel olarak değerlendirilmiştir. Hem beyin hem de pankreas ekzozomlarında toplam oksidatif durum (TOS) ve Laktat dehidrojenaz (LDH) seviyelerinde anlamlı bir artış bulundu. Total antioksidan düzeyinin (TAC) kontrol grubuna göre azaldığı gözlendi (P<0.05). Gerçek Zamanlı PCR ile yapılan inceleme sonucunda hem beyin dokusunda hem de pankreas dokusunda miRNA -9 düzeylerinin önemli ölçüde arttığı ve miR-146 gen düzeylerinin önemli ölçüde aşağı regüle edildiği belirlendi (P<0.05).
Sonuç olarak, diyabetik sıçanların beyin ve pankreas dokusu eksozomlarında miRNA -9 ve -146 seviyelerinde önemli değişiklikler meydana geldi. Bu sonuçlar, diyabetik rat eksozomların miRNA düzeyinde değişikliğe neden olduğu ve bu değişikliğin nöroinflamasyonla ilişkili olabileceğini göstermektedir.
Ashrafizadeh, M., Kumar, A.P., Aref, A.R., Zarrabi, A. &
Mostafavi, E. (2022). Exosomes as promising
nanostructures in diabetes mellitus: from insulin
sensitivity to ameliorating diabetic complications.
Int J Nanomedicine, 1229-1253.
Balasubramanyam, M., Aravind, S., Gokulakrishnan, K.,
Prabu, P., Sathishkumar, C., Ranjani, H. &
Mohan, V. (2011). Impaired miR-146a expression
links subclinical inflammation and insulin resistance
in Type 2 diabetes. Molecular and cellular
biochemistry, 351, 197-205.
Baldeón, R.L., Weigelt, K., De Wit, H., Ozcan, B., van
Oudenaren, A., Sempertegui, F., Sijbrands, E.,
Grosse, L., Freire, W. & Drexhage, H.A. (2014).
Decreased serum level of miR-146a as sign of
chronic inflammation in type 2 diabetic patients.
PLoS One, 9(12), e115209.
Bazzoni, F., Rossato, M., Fabbri, M., Gaudiosi, D., Mirolo,
M., Mori, L., Tamassia, N., Mantovani, A.,
Cassatella, M.A., & Locati, M. (2009). Induction
and regulatory function of miR-9 in human
monocytes and neutrophils exposed to
proinflammatory signals. Proceedings of the
National Academy of Sciences, 106(13), 5282-5287.
Biessels, G. J. & Reagan, L. P. (2015). Hippocampal insulin
resistance and cognitive dysfunction. Nature
Reviews Neuroscience, 16(11), 660-671.
Brownlee, M. (2005). The pathobiology of diabetic
complications: a unifying mechanism. Diabetes,
54(6), 1615-1625.
Butler, A.E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza,
R.A. & Butler, P.C. (2003). β-cell deficit and
increased β-cell apoptosis in humans with type 2
diabetes. Diabetes, 52(1), 102-110.
Chatterjee, S., Khunti, K. & Davies, M.J. (2017). Type 2
diabetes. The lancet, 389(10085), 2239-2251.
Chen, W., Lou, J., Evans, E.A. & Zhu, C. (2012). Observing
force-regulated conformational changes and ligand
dissociation from a single integrin on cells. Journal
of Cell Biology, 199(3), 497-512.
Collaboration, N.R.F. (2017). Trends in obesity and diabetes
across Africa from 1980 to 2014: an analysis of
pooled population-based studies. International
journal of epidemiology, 46(5), 1421-1432.
Finnegan, E. J. & Matzke, M. A. (2003). The small RNA
world. Journal of cell science, 116(23), 4689-4693.
Ganesh Yerra, V., Negi, G., Sharma, S. & Kumar, A.
(2013). Potential therapeutic effects of the
simultaneous targeting of the Nrf2 and NF-κB
pathways in diabetic neuropathy. Redox Biol 1: 394-
397. In.
Genc, S., Yagci, T., Vageli, D. P., Dundar, R., Doukas, P.
G., Doukas, S. G., Tolia, M., Chatzakis, N.,
Tsatsakis, A. & Taghizadehghalehjoughi, A.
(2023). Exosomal MicroRNA-223, MicroRNA-146,
and MicroRNA-21 Profiles and Biochemical
Changes in Laryngeal Cancer. ACS Pharmacology
& Translational Science, 6(5), 820-828.
Gilbert, R.E. & Cooper, M.E. (1999). The tubulointerstitium
in progressive diabetic kidney disease: more than an
aftermath of glomerular injury? Kidney
international, 56(5), 1627-1637.
Guo, H.-Y., Cheng, A.-C., Wang, M.-S., Yin, Z.-Q. & Jia,
R.-Y. (2020). Exosomes: potential therapies for
disease via regulating TLRs. Mediators of
Inflammation, 2020.
Haligur, M., Topsakal, S. & Ozmen, O. (2012). Early
degenerative effects of diabetes mellitus on
pancreas, liver, and kidney in rats: an
immunohistochemical study. Journal of diabetes
research, 2012.
Impey, S., McCorkle, S.R., Cha-Molstad, H., Dwyer, J.M.,
Yochum, G.S., Boss, J.M., McWeeney, S., Dunn,
J.J., Mandel, G. & Goodman, R.H. (2004).
Defining the CREB regulon: a genome-wide
analysis of transcription factor regulatory regions.
Cell, 119(7), 1041-1054.
Kaplan, A., Cetin, M., Orgul, D., Hacimufnewlu, A., &
Hekimoglu, S. (2019). Formulation and In Vitro
Evaluation of Topical Nanoemulsion based Gels
Containing Daidzein. Journal of Drug Delivery
Science and Technology, 19, 30263.
Kluiver, J., van den Berg, A., de Jong, D., Blokzijl, T.,
Harms, G., Bouwman, E., Jacobs, S., Poppema, S.
& Kroesen, B.-J. (2007). Regulation of primicroRNA BIC transcription and processing in
Burkitt lymphoma. Oncogene, 26(26), 3769-3776.
Kodl, C. T., & Seaquist, E. R. (2008). Cognitive dysfunction
and diabetes mellitus. Endocrine reviews, 29(4),
494-511.
Kong, L., Zhu, J., Han, W., Jiang, X., Xu, M., Zhao, Y.,
Dong, Q., Pang, Z., Guan, Q. & Gao, L. (2011).
Significance of serum microRNAs in pre-diabetes
and newly diagnosed type 2 diabetes: a clinical
study. Acta diabetologica, 48, 61-69.
L Isola, A. & Chen, S. (2017). Exosomes: the messengers of
health and disease. Current neuropharmacology,
15(1), 157-165.
Li, Q., Zemel, E., Miller, B. & Perlman, I. (2002). Early
retinal damage in experimental diabetes:
electroretinographical and morphological
observations. Experimental eye research, 74(5),
615-625.
Lopes, M.B., Freitas, R.C., Hirata, M.H., Hirata, R.D.,
Rezende, A.A., Silbiger, V.N., Bortolin, R.H. &
Luchessi, A.D. (2017). mRNA-miRNA integrative
analysis of diabetes-induced cardiomyopathy in rats.
Frontiers in Bioscience-Scholar, 9(2), 194-229.
Masiello, P., Broca, C., Gross, R., Roye, M., Manteghetti,
M., Hillaire-Buys, D., Novelli, M., & Ribes, G.
(1998). Experimental NIDDM: development of a
new model in adult rats administered streptozotocin
and nicotinamide. Diabetes, 47(2), 224-229.
Mijnhout, G., Scheltens, P., Diamant, M., Biessels, G.,
Wessels, A., Simsek, S., Snoek, F., & Heine, R.
(2006). Diabetic encephalopathy: a concept in need
of a definition. Diabetologia, 49, 1447-1448.
Muriach, M., Flores-Bellver, M., Romero, F.J. & Barcia,
J.M. (2014). Diabetes and the brain: oxidative stress,
inflammation, and autophagy. Oxidative medicine
and cellular longevity, 2014.
Patel, S. & Santani, D. (2009). Role of NF-κB in the
pathogenesis of diabetes and its associated
complications. Pharmacological Reports, 61(4),
595-603.
Reed, M., Meszaros, K., Entes, L., Claypool, M., Pinkett,
J., Gadbois, T. & Reaven, G. (2000). A new rat
model of type 2 diabetes: the fat-fed, streptozotocintreated rat. Metabolism-Clinical and Experimental,
49(11), 1390-1394.
Sakshi, S., Jayasuriya, R., Ganesan, K., Xu, B. &
Ramkumar, K. M. (2021). Role of circRNAmiRNA-mRNA interaction network in diabetes and
its associated complications. Molecular TherapyNucleic Acids, 26, 1291-1302.
Samanta, S., Rajasingh, S., Drosos, N., Zhou, Z., Dawn, B.
& Rajasingh, J. (2018). Exosomes: new molecular
targets of diseases. Acta Pharmacol Sin, 39(4), 501-
513.
Shawky, L.M., Morsi, A.A., El Bana, E. & Hanafy, S. M.
(2019). The biological impacts of sitagliptin on the
pancreas of a rat model of type 2 diabetes mellitus:
Drug interactions with metformin. Biology, 9(1), 6.
Sıdıka, G., Cakir, Z., Taghizadehghalehjoughi, A., Yeşim,
Y., Jalili, K. & HACIMÜFTÜOĞLU, A. (2021).
Investigation of the Exosome-Based Drug Delivery
System Potential in theTreatment of Glioblastoma in
vitro Experimental Models. International Journal of
Life Sciences and Biotechnology, 4(3), 451-467.
Szkudelski, T. (2012). Streptozotocin–nicotinamide-induced
diabetes in the rat. Characteristics of the
experimental model. Experimental biology and
medicine, 237(5), 481-490.
Taganov, K.D., Boldin, M.P., Chang, K.-J. & Baltimore,
D. (2006). NF-κB-dependent induction of
microRNA miR-146, an inhibitor targeted to
signaling proteins of innate immune responses.
Proceedings of the National Academy of Sciences,
103(33), 12481-12486.
Targher, G., & Byrne, C. D. (2017). Non-alcoholic fatty
liver disease: an emerging driving force in chronic
kidney disease. Nature Reviews Nephrology, 13(5),
297-310.
Wang-Fischer, Y., & Garyantes, T. (2018). Improving the
reliability and utility of streptozotocin-induced rat
diabetic model. Journal of diabetes research, 2018.
Westermark, P., Wernstedt, C., Wilander, E., Hayden, D.
W., O'Brien, T. D. & Johnson, K. H. (1987).
Amyloid fibrils in human insulinoma and islets of
Langerhans of the diabetic cat are derived from a
neuropeptide-like protein also present in normal islet
cells. Proceedings of the National Academy of
Sciences, 84(11), 3881-3885.
Wong, C.H., Wanrooy, B.J. & Bruce, D.G. (2018).
Neuroinflammation, type 2 diabetes, and dementia.
In Type 2 Diabetes and Dementia (pp. 195-209).
Elsevier.
Wu, K.K. & Huan, Y. (2008). Streptozotocin‐induced
diabetic models in mice and rats. Current protocols
in pharmacology, 40(1), 5.47. 41-45.47. 14.
Ye, J., Zhu, J., Chen, H., Qian, J., Zhang, L., Wan, Z.,
Chen, F., Sun, S., Li, W. & Luo, C. (2020). A novel
lncRNA‐LINC01116 regulates tumorigenesis of
glioma by targeting VEGFA. Int J Cancer, 146(1),
248-261.
Yeni, Y., Taghizadehghalehjoughi, A., Genc, S.,
Hacimuftuoglu, A., Yildirim, S. & Bolat, I. (2023).
Glioblastoma cell-derived exosomes induce cell
death and oxidative stress in primary cultures of
olfactory neurons. Role of redox stress. Mol Biol
Rep, 50(5), 3999-4009.
Yeni, Y., Taghizadehghalehjoughi, A., Genc, S.,
Hacimuftuoglu, A., Yildirim, S. & Bolat, I. (2023).
Glioblastoma cell-derived exosomes induce cell
death and oxidative stress in primary cultures of
olfactory neurons. Role of redox stress. Mol Biol
Rep, 50(5), 3999-4009.
Zhang, N., He, F., Li, T., Chen, J., Jiang, L., Ouyang, X.-
P. & Zuo, L. (2021). Role of exosomes in brain
diseases. Front Cell Neurosci, 15, 743353.
Zhao, Y., Krishnamurthy, B., UA Mollah, Z., WH Kay, T.,
& E Thomas, H. (2011). NF-κB in type 1 diabetes.
Inflammation & Allergy-Drug Targets (Formerly
Current Drug Targets-Inflammation &
Allergy)(Discontinued), 10(3), 208-217.
Genç, S., & Taghizadehghalehjoughi, A. (2023). Comparison of Brain and Pancreas Tissues Exosome derived -miRNA -9 and -146 levels in Healthy and Diabetes Rats. Journal of Anatolian Environmental and Animal Sciences, 8(4), 671-678. https://doi.org/10.35229/jaes.1358883