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Long-term high-fat high-fructose diet induces type 2 diabetes in rats through oxidative stress

ABSTRACT: 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 in-flammatory status. The rats developed metabolic disorders, and the size of the islets in the pancreas increased after three 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. Plasma oxidative parameters and nucleic acid oxidation markers (8-oxo-Gsn and 8-oxo-dGsn) elevated before inflammatory factors, suggesting that the HFHF diet increased the degree of oxidative stress before affecting in-flammation. Single-cell RNA sequencing also verified that the transcriptional level of oxidoreduc-tase changed differently in islet sub-populations 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

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE201900 | GEO | 2022/06/15

REPOSITORIES: GEO

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