PMID- 35677051 OWN - NLM STAT- MEDLINE DCOM- 20220610 LR - 20220716 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Enhanced T Cell Glucose Uptake Is Associated With Progression of Beta-Cell Function in Type 1 Diabetes. PG - 897047 LID - 10.3389/fimmu.2022.897047 [doi] LID - 897047 AB - BACKGROUND: Abnormal intracellular glucose/fatty acid metabolism of T cells has tremendous effects on their immuno-modulatory function, which is related to the pathogenesis of autoimmune diseases. However, the association between the status of intracellular metabolism of T cells and type 1 diabetes is unclear. This study aimed to investigate the uptake of glucose and fatty acids in T cells and its relationship with disease progression in type 1 diabetes. METHODS: A total of 86 individuals with type 1 diabetes were recruited to detect the uptake of glucose and fatty acids in T cells. 2-NBDG uptake and expression of glucose transporter 1 (GLUT1); or BODIPY uptake and expression of carnitine palmitoyltransferase 1A(CPT1A) were used to assess the status of glucose or fatty acid uptake in T cells. Patients with type 1 diabetes were followed up every 3-6 months for 36 months, the progression of beta-cell function was assessed using generalized estimating equations, and survival analysis was performed to determine the status of beta-cell function preservation (defined as 2-hour postprandial C-peptide >200 pmol/L). RESULTS: Patients with type 1 diabetes demonstrated enhanced intracellular glucose uptake of T cells as indicated by higher 2NBDG uptake and GLUT1 expression, while no significant differences in fatty acid uptake were observed. The increased T cells glucose uptake is associated with lower C-peptide and higher hemoglobin A1c levels. Notably, patients with low T cell glucose uptake at onset maintained high levels of C-peptide within 36 months of the disease course [fasting C-petite and 2-hour postprandial C-peptide are 60.6 (95%CI: 21.1-99.8) pmol/L and 146.3 (95%CI: 14.1-278.5) pmol/L higher respectively], And they also have a higher proportion of beta-cell function preservation during this follow-up period (P<0.001). CONCLUSIONS: Intracellular glucose uptake of T cells is abnormally enhanced in type 1 diabetes and is associated with beta-cell function and its progression. CI - Copyright (c) 2022 Tang, Zhong, Fan, Xie, Li and Li. FAU - Tang, Rong AU - Tang R AD - National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China. FAU - Zhong, Ting AU - Zhong T AD - National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China. FAU - Fan, Li AU - Fan L AD - National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China. FAU - Xie, Yuting AU - Xie Y AD - National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China. FAU - Li, Juan AU - Li J AD - National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China. FAU - Li, Xia AU - Li X AD - National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220523 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (C-Peptide) RN - 0 (Fatty Acids) RN - 0 (Glucose Transporter Type 1) RN - 0 (Insulin) RN - IY9XDZ35W2 (Glucose) SB - IM MH - C-Peptide/metabolism MH - *Diabetes Mellitus, Type 1/complications MH - *Diabetes Mellitus, Type 2/metabolism MH - Fatty Acids MH - Glucose/metabolism MH - Glucose Transporter Type 1 MH - Humans MH - Insulin/metabolism MH - T-Lymphocytes/metabolism PMC - PMC9168918 OTO - NOTNLM OT - T cell OT - beta-cell function OT - cellular glucose uptake OT - immunometabolism OT - type 1 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/06/10 06:00 MHDA- 2022/06/11 06:00 PMCR- 2022/01/01 CRDT- 2022/06/09 02:06 PHST- 2022/03/15 00:00 [received] PHST- 2022/04/22 00:00 [accepted] PHST- 2022/06/09 02:06 [entrez] PHST- 2022/06/10 06:00 [pubmed] PHST- 2022/06/11 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.897047 [doi] PST - epublish SO - Front Immunol. 2022 May 23;13:897047. doi: 10.3389/fimmu.2022.897047. eCollection 2022.