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Protective mechanism of Ramulus Mori (Sangzhi) Alkaloids on T2DM combined with MASLD by hepatic lipid metabolism and gut microbiota analyses
Xuelian Fu, Jing Zhao, Han Meng, Mengting Wang, Hong Qiao
2025, 5(4): 242-251. doi: 10.1515/fzm-2025-0026
Keywords: Ramulus Mori (Sangzhi) Alkaloids, gut microbiota, lipidomics analysis
  Background and objective  Both type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) are known to be influenced by environmental and lifestyle factors. Ramulus Mori (Sangzhi) alkaloids (SZ-A) are effective hypoglycemic agents. Recent studies suggest that SZ-A may improve T2DM, MASLD, and metabolic syndrome, but the underlying mechanisms remain unclear. This study aimed to investigate whether SZ-A can modulate hepatic lipid metabolism and gut microbiota in a mouse model of T2DM combined with MASLD.  Methods  A combined T2DM-MASLD mouse model was established using a high-fat diet and streptozotocin injection. Liver morphology and histology were assessed using a portable small-animal ultrasound imaging system, hematoxylin and eosin (H&E) staining, and Oil Red O staining. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured using standard assay kits. Gut microbiota composition was analyzed by 16S rRNA sequencing, and hepatic lipid metabolites were profiled using liquid chromatographymass spectrometry (LC-MS)MS.  Results  SZ-A improved liver function by ameliorating morphological and structural abnormalities, reducing lipid droplet accumulation, and lowering serum levels of TG, TC, LDL, ALT, and AST. It also led to decreased hepatic ultrasound echo intensity compared to the kidney. Additionally, SZ-A helped restore gut microbiota balance, including a partial reversal of the Firmicutes/Bacteroidetes ratio. Lipidomic analysis revealed that SZ-A downregulated most TG and diglycerides (DG), while upregulating phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the model group.  Conclusions  SZ-A partially alleviates liver injury in T2DM-MASLD mice by modulating hepatic lipid metabolism and gut microbiota composition.
Association of point in range with β-cell function and insulin sensitivity of type 2 diabetes mellitus in cold areas
Yanan Ni, Dan Liu, Xiaona Zhang, Hong Qiao
2023, 3(4): 242-252. doi: 10.2478/fzm-2023-0031
Keywords: time in range, points in range, self-monitoring of blood glucose, β-cell function, insulin sensitivity
  Background and Objective   Self-monitoring of blood glucose (SMBG) is crucial for achieving a glycemic target and upholding blood glucose stability, both of which are the primary purpose of anti-diabetic treatments. However, the association between time in range (TIR), as assessed by SMBG, and β-cell insulin secretion as well as insulin sensitivity remains unexplored. Therefore, this study aims to investigate the connections between TIR, derived from SMBG, and indices representing β-cell functionality and insulin sensitivity. The primary objective of this study was to elucidate the relationship between short-term glycemic control (measured as points in range [PIR]) and both β-cell function and insulin sensitivity.   Methods   This cross-sectional study enrolled 472 hospitalized patients with type 2 diabetes mellitus (T2DM). To assess β-cell secretion capacity, we employed the insulin secretion-sensitivity index-2 (ISSI-2) and (ΔC-peptide0–120/Δglucose0–120) × Matsuda index, while insulin sensitivity was evaluated using the Matsuda index and HOMA-IR. Since SMBG offers glucose data at specific point-in-time, we substituted TIR with PIR. According to clinical guidelines, values falling within the range of 3.9–10 mmol were considered "in range, " and the corresponding percentage was calculated as PIR.   Results   We observed significant associations between higher PIR quartiles and increased ISSI-2, (ΔC-peptide0–120/Δglucose0–120) × Matsuda index, Matsuda index (increased) and HOMA-IR (decreased) (all P < 0.001). PIR exhibited positive correlations with log ISSI-2 (r = 0.361, P < 0.001), log (ΔC-peptide0–120/Δglucose0–120) × Matsuda index (r = 0.482, P < 0.001), and log Matsuda index (r = 0.178, P < 0.001) and negative correlations with log HOMA-IR (r = -0.288, P < 0.001). Furthermore, PIR emerged as an independent risk factor for log ISSI-2, log (ΔC-peptide0–120/Δglucose0–120) × Matsuda index, log Matsuda index, and log HOMA-IR.   Conclusion   PIR can serve as a valuable tool for assessing β-cell function and insulin sensitivity.