PMID- 37650181 OWN - NLM STAT- MEDLINE DCOM- 20230901 LR - 20230901 IS - 0578-1426 (Print) IS - 0578-1426 (Linking) VI - 62 IP - 9 DP - 2023 Sep 1 TI - [The impact of human umbilical cord-derived mesenchymal stem cells on the pancreatic function of type 2 diabetic mice and their regulatory role on NLRP3 inflammasomes]. PG - 1077-1084 LID - 10.3760/cma.j.cn112138-20221225-00955 [doi] AB - Objective: To investigate the effect and regulation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on islets function and NOD-like receptor family, pyrin domain containing 3 (NLRP3) and autophagy in type 2 diabetic mellitus (T2DM) mice. Methods: Experimental study. Twenty, 8-week-old, male C57BL/6J mice were selected and divided into a normal control group (n=5) and a high-fat feeding modeling group (n=15). The model of T2DM was established by high-fat feeding combined with intraperitoneal injection of low-dose streptozotocin. After successful modeling, those mice were divided into a diabetes group (n=7) and a UC-MSCs treatment group (n=7). The UC-MSCs treatment group was given UC-MSCs (1x10(6)/0.2 ml phosphate buffer solution) by tail vein infusion once a week for a total of 4 weeks; the diabetes group was injected with the same amount of normal saline, and the normal control group was not treated. One week after the treatment, mice underwent intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and then the mice were sacrificed to obtain pancreatic tissue to detect the expressions of interleukin-1beta (IL-1beta) and pancreatic and duodenal homeobox 1 (PDX-1) by immunofluorescence. The bone marrow-derived macrophages were stimulated with lipopolysaccharide and adenosine triphosphate (experimental group) in vitro, then co-cultured with UC-MSCs for 24 h (treatment group). After the culture, enzyme-linked immunosorbent assay was used to detect the secretion level of IL-1beta in the supernatant, and immunofluorescence staining was used to detect the expression of NLRP3 inflammasome, and related autophagy proteins. Statistical analysis was performed using unpaired one-way analysis of variance, repeated measure analysis of variance. Results: In vivo experiments showed that compared with the diabetes group, the UC-MSCs treatment group partially repaired islet structure, improved glucose tolerance and insulin sensitivity (all P<0.05), and the expression of PDX-1 increased and IL-1beta decreased in islets under confocal microscopy. In vitro experiments showed that compared with the experimental group, the level of IL-1beta secreted by macrophages in the treatment group was decreased [(85.9+/-74.6) pg/ml vs. (883.4+/-446.2) pg/ml, P=0.001], the expression of NLRP3 inflammasome and autophagy-related protein P62 was decreased, and the expressions of microtubule-associated protein 1 light chain 3beta (LC3) and autophagy effector Beclin-1 were increased under confocal microscopy. Conclusions: UC-MSCs can reduce the level of pancreatic inflammation in T2DM mice, preserving pancreatic function. This might be associated with the ability of UC-MSCs to inhibit the activity of NLRP3 inflammasomes in macrophages and enhance autophagy levels. FAU - Wang, J AU - Wang J AD - Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Yin, Y Q AU - Yin YQ AD - Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Cheng, Y AU - Cheng Y AD - Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Li, B AU - Li B AD - Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Su, W L AU - Su WL AD - Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Yu, S Y AU - Yu SY AD - Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Xue, J AU - Xue J AD - Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Gu, Y L AU - Gu YL AD - Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Zhang, H X AU - Zhang HX AD - Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Zhang, L X AU - Zhang LX AD - Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Zang, L AU - Zang L AD - Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Mu, Y M AU - Mu YM AD - Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. LA - chi GR - 81900704/National Natural Science Foundation of China/ GR - CYJZ202135/Beijing Chao-Yang Hospital Golden Seeds Foundation/ PT - English Abstract PT - Journal Article PL - China TA - Zhonghua Nei Ke Za Zhi JT - Zhonghua nei ke za zhi JID - 16210490R RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) SB - IM MH - Humans MH - Male MH - Animals MH - Mice MH - Mice, Inbred C57BL MH - Inflammasomes MH - NLR Family, Pyrin Domain-Containing 3 Protein MH - *Diabetes Mellitus, Experimental MH - *Mesenchymal Stem Cells MH - *Diabetes Mellitus, Type 2 EDAT- 2023/08/31 06:42 MHDA- 2023/09/01 06:43 CRDT- 2023/08/31 04:22 PHST- 2023/09/01 06:43 [medline] PHST- 2023/08/31 06:42 [pubmed] PHST- 2023/08/31 04:22 [entrez] AID - 10.3760/cma.j.cn112138-20221225-00955 [doi] PST - ppublish SO - Zhonghua Nei Ke Za Zhi. 2023 Sep 1;62(9):1077-1084. doi: 10.3760/cma.j.cn112138-20221225-00955.