PMID- 29197589 OWN - NLM STAT- MEDLINE DCOM- 20171226 LR - 20191210 IS - 1879-0038 (Electronic) IS - 0378-1119 (Linking) VI - 642 DP - 2018 Feb 5 TI - SIRT6 expression and oxidative DNA damage in individuals with prediabetes and type 2 diabetes mellitus. PG - 542-548 LID - S0378-1119(17)31036-3 [pii] LID - 10.1016/j.gene.2017.11.071 [doi] AB - Sirtuins (SIRTs) is a family of NAD(+) dependent histone deacetylases. SIRT6 takes play in glucose homeostasis, genomic stability and DNA repair. Although increased oxidative DNA damage and decreased DNA repair activity were determined in diabetes mellitus, the possible relation between level of oxidative DNA damage and SIRT6 expression has not been investigated so far. We determined SIRT6 expression and urinary 8-hydroxy deoxyguanosine (8-OHdG) levels, marker of oxidative DNA damage, in cases with prediabetes (PreDM) and type 2 diabetes mellitus (T2DM). SIRT6 gene expression was determined in peripheral blood leukocytes of 70 patients with type 2 diabetes, 50 cases in prediabetic stage and 40 healthy subjects. SIRT6 mRNA levels were determined by quantitive real time- polymerase chain reaction. SIRT6 protein was detected by immunocytochemical staining. Urinary 8-hydroxy deoxyguanosine (8-OHdG) levels were measured by ELISA. There was no significant difference between groups for SIRT6 mRNA level. SIRT6 immunopositivity in T2DM group was lower when compared to those in preDM group (P<0.05). SIRT6 positive cell number in T2DM and preDM groups were lower in comparison to control group (P<0.01 for both), however, when study groups were subdivided into two groups according to their age, the difference between preDM and control groups disappeared in both mid-aged and old-aged groups. The urinary 8-OHdG level was found to be higher in the T2DM group in comparison to preDM group (P<0.05). When age is taken into consideration, urinary 8-OHdG level in the T2DM group was found to be higher than those in both preDM and control groups in the old-aged cases but no significant difference was determined between groups in the mid-aged cases. There was no relation between SIRT6 expression and urinary 8-OHDG excretion. It was concluded that SIRT6 may take play in development of T2DM but this effect seems to be independent from repair of oxidative DNA damage. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Caliskan, Z AU - Caliskan Z AD - Department of Medical Biochemistry, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey; Department of Medical Biochemistry, Istanbul Yeni Yuzyil University Medical Faculty, Istanbul, Turkey. FAU - Mutlu, T AU - Mutlu T AD - Department of Medical Biology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey. FAU - Guven, M AU - Guven M AD - Department of Medical Biology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey. FAU - Tuncdemir, M AU - Tuncdemir M AD - Department of Medical Biology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey. FAU - Niyazioglu, M AU - Niyazioglu M AD - Department of Internal Medicine, Istanbul Education and Research Hospital, Istanbul, Turkey. FAU - Hacioglu, Y AU - Hacioglu Y AD - Department of Internal Medicine, Istanbul Education and Research Hospital, Istanbul, Turkey. FAU - Dincer, Y AU - Dincer Y AD - Department of Medical Biochemistry, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey. Electronic address: yldz.dincer@gmail.com. LA - eng PT - Journal Article DEP - 20171129 PL - Netherlands TA - Gene JT - Gene JID - 7706761 RN - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine) RN - EC 3.5.1.- (SIRT6 protein, human) RN - EC 3.5.1.- (Sirtuins) RN - G9481N71RO (Deoxyguanosine) SB - IM MH - 8-Hydroxy-2'-Deoxyguanosine MH - Adult MH - Aged MH - Aged, 80 and over MH - DNA Damage MH - Deoxyguanosine/analogs & derivatives/urine MH - Diabetes Mellitus, Type 2/genetics/*metabolism/urine MH - Down-Regulation MH - Female MH - Humans MH - Male MH - Middle Aged MH - Oxidative Stress MH - Prediabetic State/genetics/*metabolism/urine MH - Sirtuins/*genetics/*metabolism OTO - NOTNLM OT - 8-hydroxy deoxyguanosine OT - DNA repair OT - Diabetes mellitus OT - Oxidative stress OT - SIRT6 OT - Sirtuins EDAT- 2017/12/05 06:00 MHDA- 2017/12/27 06:00 CRDT- 2017/12/04 06:00 PHST- 2017/05/23 00:00 [received] PHST- 2017/10/25 00:00 [revised] PHST- 2017/11/28 00:00 [accepted] PHST- 2017/12/05 06:00 [pubmed] PHST- 2017/12/27 06:00 [medline] PHST- 2017/12/04 06:00 [entrez] AID - S0378-1119(17)31036-3 [pii] AID - 10.1016/j.gene.2017.11.071 [doi] PST - ppublish SO - Gene. 2018 Feb 5;642:542-548. doi: 10.1016/j.gene.2017.11.071. Epub 2017 Nov 29.