Affiliations 

  • 1 Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Federal Territory of Kuala Lumpur 56000, Malaysia
  • 2 Faculty of Pharmaceutical Sciences, UCSI University, Federal Territory of Kuala Lumpur 56000, Malaysia
  • 3 Faculty of Pharmaceutical Sciences, Department of Organic Chemistry, Medical University of Silesia, Jagiellonska Str. 4, 41-200 Sosnowiec, Poland
  • 4 Chemistry Department, College of Science & Mathematics, Mindanao State University-Iligan Institute of Technology, Iligan City 9200, Philippines
  • 5 Department of Chemistry, College of Natural Sciences and Mathematics, Mindanao State University-Main Campus, Marawi City 9700, Philippines
Pharmaceuticals (Basel), 2022 Oct 25;15(11).
PMID: 36355489 DOI: 10.3390/ph15111317

Abstract

(1) Insulin resistance, a symptom of type 2 diabetes mellitus (T2DM), is caused by the inactivation of the insulin signaling pathway, which includes IRS-PI3K-IRS-1-PKC-AKT2 and GLUT4. Metformin (biguanide) and glimepiride (sulfonylurea) are both drugs that are derivatives of urea, and they are widely used as first-line drugs for the treatment of type 2 diabetes mellitus. Palmatine has been previously reported to possess antidiabetic and antioxidant properties. (2) The current study compared palmatine to metformin and glimepiride in a type 2 diabetes model for ADME and insulin resistance via the PI3K/Akt/GLUT4 signaling pathway: in vitro, in vivo, ex vivo, and in silico molecular docking. (3) Methods: Differentiated L6 skeletal muscle cells and soleus muscle tissue were incubated in standard tissue culture media supplemented with high insulin and high glucose as a cellular model of insulin resistance, whilst streptozotocin (STZ)-induced Sprague Dawley rats were used as the diabetic model. The cells/tissue/animals were treated with palmatine, while glimepiride and metformin were used as standard drugs. The differential gene expression of PI3K, IRS-1, PKC-α, AKT2, and GLUT4 was evaluated using qPCR. (4) Results: The results revealed that the genes IRS-PI3K-IRS-1-PKC-AKT2 were significantly down-regulated, whilst PKC-α was upregulated significantly in both insulin-resistant cells and tissue animals. Interestingly, palmatine-treated cells/tissue/animals were able to reverse these effects. (5) Conclusions: Palmatine appears to have rejuvenated the impaired insulin signaling pathway through upregulation of the gene expression of IRS-1, PI3K, AKT2, and GLUT4 and downregulation of PKC-expression, according to in vitro, in vivo, and ex vivo studies.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.