<p>Guava Leaf Extract Attenuates Insulin Resistance via the PI3K/Akt Signaling Pathway in a Type 2 Diabetic Mouse Model</p>

Abstract

Background and Objective: Insulin resistance is well known to exhibit essential effects on the progression of diabetes mellitus (DM). Guava leaf was also reported to exhibit antidiabetic effects including decreasing blood glucose. Therefore, this present study aims to explore the role guava leaf extract (GLE) plays in insulin resistance and its mechanism of action via the PI3K/Akt signaling pathway. Methods: KK-Ay mice is a spontaneous genetic type 2 diabetes mouse model induced by feeding a high fat and high sugar diet. Mice were randomly assigned into three groups: diabetic mice (DM), DM + MET (diabetic mice treated with metformin) and DM + GLE (diabetic mice treated with GLE) groups. After 8 weeks of treatment, body weight and levels of fasting plasma glucose (FPG), fasting insulin and lipids in plasma were measured. Mice were sacrificed and mRNA and protein expression of insulin receptor substrate1 (IRS1), phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase protein B (Akt) in livers were measured. Results: GLE markedly reduced body weight, FPG, fasting insulin and insulin resistance index but increased the insulin sensitivity index of diabetic KK-Ay mice. Moreover, GLE upregulated the expression of IRS-1, PI3K and Akt mRNAs in livers of diabetic KK-Ay mice. In addition, GLE also elevated IRS-1, PI3K, Akt, p-PI3K and p-Akt protein expression in their livers. The results of the DM + MET group were similar to those of the DM + GLE group. Conclusion: GLE plays anti-diabetic roles by ameliorating insulin resistance in KK-Ay diabetic mice and this is related to the activation of PI3K/Akt signaling pathway.

6,8-(1,3-Diaminoguanidine) luteolin and its Cr complex show hypoglycemic activities and alter intestinal microbiota composition in type 2 diabetes mice

“…37 Furthermore, in the glucose metabolism pathway, AKT-1 can regulate GSK-3β/GLUT-4 and mTOR/S6K1/IRS-1. 38,39 In this study, DAGL and DAGL·Cr upregulated the relative transcription and protein expression levels of six genes (PI3K, AKT-1, mTOR, GLUT-4, S6K1, and IRS-1) in T2DM mice and downregulated mRNA transcription and protein expression levels of GSK-3β. When PI3K is activated, it produces a second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3) on the plasma membrane, which binds to the pleckstrin homology domain of protein kinase B (PKB/AKT-1), allowing PDK1 to phosphorylate Ser308 of the AKT-1 protein.…”

Genome-wide analysis of mRNAs, lncRNAs, and circRNAs during intramuscular adipogenesis in Chinese Guizhou Congjiang pigs

“…In addition, the PI3K-Akt signaling pathway was significantly enriched on D8 relative to D0. The PI3K-Akt signaling pathway plays a role in cell proliferation, differentiation, apoptosis, glucose metabolism, and lipid metabolism [ 38 ]. The p53 signaling pathway is related to initiating DNA repair, cell cycle arrest, senescence, and apoptosis [ 39 ].…”

Psidium guajava L. leaf extract inhibits adipocyte differentiation and improves insulin sensitivity in 3T3-L1 cells

“…Obesity is characterized by increased adipose tissue mass, which is linked to the onset of insulin resistance and T2DM. Several studies have reported that oral administration of GLE reduced body weight and adipose tissue weight [ 19 20 ]. Adipose tissue mass can be expanded by adipocyte differentiation and subsequent fat accumulation [ 16 ].…”

“…During adipocyte differentiation, activation of transcription factors, including peroxisome proliferator activated receptor γ (PPARγ), CCAAT/enhancer-binding protein (C/EBP), and sterol regulatory element-binding protein-1c (SREBP-1c) are required to express lipogenic genes, such as acetyl-CoA carboxylase and fatty acid synthase (FAS) [ 18 ]. Recently, it has been reported that GLE reduced body weight gain and adipose tissue weight in diabetic rodents [ 19 20 ]. Nevertheless, little is known about whether GLE can affect adipogenesis.…”