Correlations between Insulin Receptor Substrate-1 with Phosphoinositide 3-Kinase and P38 Mitogen-Activated Protein Kinase Levels after Treatment of Diabetic Rats with Puguntano (Curanga Fel-Terrae [Merr.]) Leaf Extract

Abstract

BACKGROUND: Defects in post-receptor insulin signalling are the major cause of insulin resistance in type 2 diabetes mellitus (T2DM).
 AIM: This study aimed to investigate the correlations between insulin receptor substrate (IRS)-1 with phosphoinositide 3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK) levels after puguntano (Curanga fel-terrae [Merr.]) leaf extract treatment in a rat model of T2DM.
 METHODS: A combination of high-fat diet-feeding (HFD) and multiple low dose intraperitoneal injections of streptozotocin was used to induced T2DM in 48 Wistar rats, which were then randomly divided into control and treatment groups (n = 24 per group). Puguntano leaf extract was administered to the treatment group once daily (200 mg/kg.bw) for 10 days. IRS-1, PI3K and p38 MAPK levels were measured in skeletal muscle using sandwich ELISAs in control group after becoming T2DM and in the treatment group after 10 days of puguntano treatment. Data were analysed using the Wilcoxon test and Spearman’s correlation.
 RESULTS: IRS-1, PI3K and p38 MAPK levels were significantly higher in the treatment group than in the control group. There were also significant positive correlations between IRS-1 with PI3K and p38 MAPK levels (r = 0.375, p = 0.035; r = 0.552, p = 0.003; respectively) after the treatment.
 CONCLUSION: This study demonstrated significant positive correlations between IRS-1 with PI3K and p38 MAPK levels after puguntano leaf extract treatment of T2DM rats.

Hepatic Insulin Resistance Model in the Male Wistar Rat Using Exogenous Insulin Glargine Administration

“…ROS can activate the MAPK-ERK, an extracellular signal-regulated kinase pathway. MAPK pathway is part of the mitogenic arm of insulin signaling, which acts as a counterregulatory of metabolic signaling (minutes to hours) by a negative-feedback loop of insulin action by phosphorylation of IRS-1 on serine residues [9,65]; however, when it is found to be chronically active (days, months, or years), it is the major factor in developing IR [9]. This signaling controls diverse cellular functions, such as growth, differentiation, apoptosis, and proliferation [66].…”

An insight into PI3k/Akt pathway and associated protein–protein interactions in metabolic syndrome: A recent update

“…Thus, despite intensive efforts, further research to elucidate the molecular details of GLUT‐4 regulation is necessary. Syafril et al 118 demonstrated a positive correlation between IRS‐1 with p38/MAPK and PI3K levels in diabetic rats treated with Curanga fel‐terrae . Consistent with this finding, other studies showed that Coriolus versicolor , an efficient antidiabetic medicinal mushroom, possess significant anti‐insulin resistance and antidiabetic effects in the skeletal muscle of diabetic rat and myoblast (L6 cells).…”

“…Another signaling pathway proceeds through the phosphorylation of Shc, Grb/Sos, and activation of Ras, Raf, and MAPK isoforms ERK1 and ERK2. In contrast, this pathway contributes to the mitogenic and nuclear effects of insulin and imparts no metabolic action of insulin 45,115–119 . Each extracellular stimulus leads to the activation of MAPK following the sequential activation of MAPK kinase kinase (MAPKKK) and MAPK kinase (MAPKK).…”

“…In contrast, this pathway contributes to the mitogenic and nuclear effects of insulin and imparts no metabolic action of insulin. 45,[115][116][117][118][119] Each extracellular stimulus leads to the activation of MAPK following the sequential activation of MAPK kinase kinase (MAPKKK) and MAPK kinase (MAPKK). The MAPK are grouped into three families: p38/SAPKs (stress-activated protein kinases), JNKs (Jun amino-terminal kinases), and ERKs (extracellular-signal-regulated kinases).…”