New Treatment for Type 2 Diabetes Mellitus Using a Novel Bipyrazole Compound

Abstract

2′,3,3,5′-Tetramethyl-4′-nitro-2′H-1,3′-bipyrazole (TMNB) is a novel bipyrazole compound with unknown therapeutic potential in diabetes mellitus. This study aims to investigate the anti-diabetic effects of TMNB in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with TMNB (10 mg/kg) or (200 mg/kg) metformin for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. TMNB reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p < 0.001). TMNB abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with TMNB compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 and AMPK were upregulated following treatment with TMNB (p < 0.001, < 0.01, respectively). TMNB was able to upregulate GLUT2 and AMPK protein expression in liver (p < 0.001, < 0.001, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with TMNB compared to the vehicle controls (p < 0.001, 0.01, respectively). TMNB reduced MDA and IL-6 levels (p < 0.001), and increased GSH level (p < 0.05) in diabetic rats compared to the vehicle controls. Conclusion: TMNB ameliorates insulin resistance, oxidative stress, and inflammation in a T2D model. TMNB could represent a promising therapeutic agent to treat T2D.

The Emerging Importance of Cirsimaritin in Type 2 Diabetes Treatment

“…Glucose disposal is mediated by the effect of insulin on its receptors on the cell surfaces of insulin-sensitive tissues, particularly skeletal muscle, adipose tissues, and the liver [ 12 , 13 ]. Once the insulin receptor is activated, glucose transport over the plasma membrane occurs through different members of the glucose transporter (GLUT) family, such as GLUT 4, which is expressed in skeletal muscle and adipose tissue, and GLUT2, which is expressed in the liver [ 14 ]. Insulin resistance develops when insulin signaling is impaired; however, insulin resistance is compensated initially by increasing insulin secretion, but eventually, insulin release from pancreatic β-cells becomes insufficient for maintaining normal blood glucose concentration, which leads to T2D [ 15 ].…”