PMID- 35683981 OWN - NLM STAT- MEDLINE DCOM- 20220613 LR - 20220716 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 14 IP - 11 DP - 2022 May 24 TI - Long-Term High-Fat High-Fructose Diet Induces Type 2 Diabetes in Rats through Oxidative Stress. LID - 10.3390/nu14112181 [doi] LID - 2181 AB - Long-term consumption of a Western diet is a major cause of type 2 diabetes mellitus (T2DM). However, the effects of diet on pancreatic structure and function remain unclear. Rats fed a high-fat, high-fructose (HFHF) diet were compared with rats fed a normal diet for 3 and 18 months. Plasma biochemical parameters and inflammatory factors were used to reflect metabolic profile and inflammatory status. The rats developed metabolic disorders, and the size of the islets in the pancreas increased after 3 months of HFHF treatment but decreased and became irregular after 18 months. Fasting insulin, C-peptide, proinsulin, and intact proinsulin levels were significantly higher in the HFHF group than those in the age-matched controls. Plasmatic oxidative parameters and nucleic acid oxidation markers (8-oxo-Gsn and 8-oxo-dGsn) became elevated before inflammatory factors, suggesting that the HFHF diet increased the degree of oxidative stress before affecting inflammation. Single-cell RNA sequencing also verified that the transcriptional level of oxidoreductase changed differently in islet subpopulations with aging and long-term HFHF diet. We demonstrated that long-term HFHF diet and aging-associated structural and transcriptomic changes that underlie pancreatic islet functional decay is a possible underlying mechanism of T2DM, and our study could provide new insights to prevent the development of diet-induced T2DM. FAU - Zhao, Yue AU - Zhao Y AD - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China. AD - Graduate School of Peking Union Medical College, Beijing 100730, China. FAU - Wang, Qing-Yu AU - Wang QY AUID- ORCID: 0000-0002-9352-0923 AD - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China. FAU - Zeng, Lv-Tao AU - Zeng LT AD - Peking University Fifth School of Clinical Medicine, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China. FAU - Wang, Jing-Jing AU - Wang JJ AD - Department of Clinical Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450066, China. FAU - Liu, Zhen AU - Liu Z AD - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China. AD - Graduate School of Peking Union Medical College, Beijing 100730, China. FAU - Fan, Guo-Qing AU - Fan GQ AD - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China. AD - Graduate School of Peking Union Medical College, Beijing 100730, China. FAU - Li, Jin AU - Li J AD - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China. FAU - Cai, Jian-Ping AU - Cai JP AD - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China. AD - Graduate School of Peking Union Medical College, Beijing 100730, China. LA - eng GR - No. 82170856/National Natural Science Foundation of China/ GR - No. 2021-1-I2M-050/CAMS Innovation Fund for Medical Sciences/ GR - 2018YFC2000300/National Key R&D Program of China/ PT - Journal Article DEP - 20220524 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 30237-26-4 (Fructose) SB - IM MH - Animals MH - *Diabetes Mellitus, Type 2/etiology MH - Diet, High-Fat/adverse effects MH - Fructose/adverse effects MH - *Insulin Resistance MH - Oxidative Stress MH - Rats PMC - PMC9182436 OTO - NOTNLM OT - Western dietary pattern OT - islets OT - metabolic disorders OT - pancreas OT - single-cell RNA sequencing analysis COIS- The authors declare no conflict of interest. EDAT- 2022/06/11 06:00 MHDA- 2022/06/14 06:00 PMCR- 2022/05/24 CRDT- 2022/06/10 01:21 PHST- 2022/04/01 00:00 [received] PHST- 2022/05/13 00:00 [revised] PHST- 2022/05/20 00:00 [accepted] PHST- 2022/06/10 01:21 [entrez] PHST- 2022/06/11 06:00 [pubmed] PHST- 2022/06/14 06:00 [medline] PHST- 2022/05/24 00:00 [pmc-release] AID - nu14112181 [pii] AID - nutrients-14-02181 [pii] AID - 10.3390/nu14112181 [doi] PST - epublish SO - Nutrients. 2022 May 24;14(11):2181. doi: 10.3390/nu14112181.