PMID- 38481895 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240315 IS - 2168-8184 (Print) IS - 2168-8184 (Electronic) IS - 2168-8184 (Linking) VI - 16 IP - 2 DP - 2024 Feb TI - Studies on the Effect of Piperine on Hepatocyte Nuclear Factor 1 Alpha (HNF-1alpha) and Sterol Regulatory Element-Binding Protein 1c (SREBP-1c) Levels in High-Fat-Diet and Sucrose-Induced Type 2 Diabetes Mellitus Rats. PG - e54061 LID - 10.7759/cureus.54061 [doi] LID - e54061 AB - BACKGROUND: Piperine, a naturally occurring compound in black pepper (Piper nigrum), is known for its potential health benefits, including its reported enhancement of insulin sensitivity. However, the precise impact of piperine on hepatocyte nuclear factor 1 alpha (HNF-1alpha) and sterol regulatory element-binding protein 1c (SREBP-1c), transcription factors for insulin signaling and glucose metabolism in hepatocytes, remains unclear. OBJECTIVE: This study aims to investigate the effect of piperine, compared to metformin, on blood glucose and insulin levels by modifying the expression of hepatic HNF-1alpha and SREBP-1c in high-fat-diet (HFD) and sucrose-induced type 2 diabetes mellitus (T2DM) rats and in human Chang liver cells. METHODS: Adult male albino rats were categorized into four groups: group 1 as the control, group 2 as T2DM, group 3 as T2DM rats treated with piperine (40 mg), and group 4 as T2DM rats treated with metformin (50 mg). Fasting blood glucose (FBG) and serum insulin levels were measured using enzyme-linked immunosorbent assay (ELISA), while real-time polymerase chain reaction (RT-PCR) analysis was conducted to assess the mRNA expression of HNF-1alpha and SREBP-1c. Further, piperine was treated with normal and high glucose-induced Chang liver cells, and gene expression was analysed. Data analysis was performed using one-way analysis of variance (ANOVA), with a significance set at p<0.05. RESULTS: Treatment with piperine led to a notable decrease in blood glucose levels and circulating insulin when compared with T2DM rats (group 2). Additionally, piperine administration resulted in the upregulation of HNF-1alpha mRNA expression and downregulation of SREBP-1c mRNA levels whose effects were found to be near that of the control and standard drug metformin's effects. In vitro study also confirmed that piperine improved the HNF-1alpha expression and reduced the expression of SREBP-1c in Chang liver cells. CONCLUSION: Our findings suggest that piperine treatment effectively regulates hyperglycemic and hyperinsulinemic insulin resistance in the liver by modulating the expression of HNF-1alpha and SREBP-1c. Consequently, piperine emerges as a promising candidate for therapeutic intervention in managing T2DM. CI - Copyright (c) 2024, Zuvairiya et al. FAU - Zuvairiya, Ummu AU - Zuvairiya U AD - Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND. FAU - Jayaraman, Selvaraj AU - Jayaraman S AD - Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND. FAU - Sankaran, Kavitha AU - Sankaran K AD - Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND. FAU - Veeraraghavan, Vishnu Priya AU - Veeraraghavan VP AD - Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND. FAU - R, Gayathri AU - R G AD - Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND. LA - eng PT - Journal Article DEP - 20240212 PL - United States TA - Cureus JT - Cureus JID - 101596737 PMC - PMC10933888 OTO - NOTNLM OT - black pepper OT - gene expression OT - high-fat diet OT - insulin resistance OT - male wistar rat COIS- The authors have declared that no competing interests exist. EDAT- 2024/03/14 06:46 MHDA- 2024/03/14 06:47 PMCR- 2024/02/12 CRDT- 2024/03/14 04:16 PHST- 2023/08/20 00:00 [received] PHST- 2024/02/10 00:00 [accepted] PHST- 2024/03/14 06:47 [medline] PHST- 2024/03/14 06:46 [pubmed] PHST- 2024/03/14 04:16 [entrez] PHST- 2024/02/12 00:00 [pmc-release] AID - 10.7759/cureus.54061 [doi] PST - epublish SO - Cureus. 2024 Feb 12;16(2):e54061. doi: 10.7759/cureus.54061. eCollection 2024 Feb.