Anti-Diabetic Effects of Jiang Tang Xiao Ke Granule via PI3K/Akt Signalling Pathway in Type 2 Diabetes KKAy Mice

Abstract

Jiang Tang Xiao Ke (JTXK) granule, a Chinese herbal formula, has been used clinically to treat type 2 diabetes (T2DM) for decades. Our previous studies showed that JTXK granule exhibited anti-diabetic and anti-oxidative functions in experimental diabetic rats induced by a high fat diet and streptozotocin. However, the underlying mechanisms remain poorly understood. Herein, we aimed to investigate the therapeutic effect of JTXK granule on T2DM KKAy mice and the possible associations with skeletal muscle in the current study. Our results showed that JTXK granule significantly reduced food intake and body weight in T2DM KKAy mice. JTXK granule treatment also decreased the blood glucose and HbA1c levels and increased the insulin sensitivity in a time-dependent manner. Additionally, it ameliorated hyperlipidaemia and induced a lower free fatty acid level, displaying an effect on disorders of lipid metabolism. JTXK granule significantly increased the expression of insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K), protein kinase B (PKB/Akt) and glucose transporter 4 (Glut4) and decreased the expression of glycogen synthase kinase 3β (GSK3β). We concluded that JTXK granule is an effective drug for T2DM through regulating the PI3K/Akt signalling pathway in skeletal muscle.

Acyl and Benzyl‐C‐β‐D‐Glucosides: Synthesis and Biostudies for Glucose‐Uptake‐Promoting Activity in C2C12 Mytotubes

“…On the other hand, PI3K is a downsignaling molecule in the insulin cascade which is known to enhance glucose uptake through GLUT4 mRNA expression and translocation. [30] Although, we have observed an increase in PI3K mRNA expression with metformin and pioglitazone, as also reported by others, [31,32] the same was not observed with our set of compounds (5a-d). Compounds 5a, 5b, 5c and 5d enhanced glucose uptake by increasing PPAR-γ mRNA expression by approximately 1.…”

“…At stirring isopropyl bromide (0.325 mL, 3.46 mmol) was added slowly, after 5 min the mixture was strongly self-heated As the magnesium turnings were finished, benzo[d]thiazole (0.285 mL, 2.6 mmol) was added to the reaction mixture at 0°C slowly and stirring was continued for [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] min at the same temperature. The flask was pre-heated under vacuum to activate the magnesium and anhydrous THF (25 mL) was added.…”

“…The reaction mixture was stirred under H 2 atmosphere (balloon pressure) for [24][25][26][27][28][29][30][31][32][33][34][35][36] h. The solution was filtered through a pad of celite, and the filtrate was concentrated under reduced pressure. in MeOH (5 mL) was added Pd/C (0.1 eq., 10 mol-%) followed by catalytic amount of concd.…”

Effects of Aerobic Exercise Combined with Panaxatriol Derived from Ginseng on Insulin Resistance and Skeletal Muscle Mass in Type 2 Diabetic Mice

“…Its expression is decreased by the activation of insulin signaling pathway and facilitated by the increase in the protein expression of tumor necrosis factor-␣ (TNF-␣) in skeletal muscle (51)(52)(53). KKAy mice have been reported to show decreased proteins level of insulin signaling pathway and increased mRNA expression of TNF-␣ in skeletal muscle (54)(55)(56). Therefore, it was suggested that KKAy mice might upregulate the expression of Atrogin1 in skeletal muscle.…”

Improvement of high-glucose and insulin resistance of chromium malate in 3T3-L1 adipocytes by glucose uptake and insulin sensitivity signaling pathways and its mechanism

“…35,36 The lower levels of IRS-1 and PI3K in insulin signal transduction pathway with defects were found in T2DM. 37 Peroxisome proliferatoractivated receptor gamma (PPAR gamma) can enhance insulin sensitivity in muscle and adipose tissues, and some of exogenous potent PPARg ligands are used as medicines to T2DM. 38 p38-MAPK can regulate glucose metabolism.…”