Eugenosedin-A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide-induced diabetic rats

• Published in: The Kaohsiung journal of medical sciences Vol. 34; no. 3; pp. 142 - 149
• Main Authors: Shen, Kuo-Ping, Lin, Hui-Li, Yen, Hsueh-Wei, Hsieh, Su-Ling, An, Li-Mei, Wu, Bin-Nan
• Format: Journal Article
• Language: English
• Published: China (Republic : 1949- ) Elsevier Taiwan 01-03-2018; Wiley
• Subjects: Animals; Blood Glucose - metabolism; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - pathology; Diet, High-Fat - adverse effects; Eugenosedin-A; Gene Expression Regulation; Glucokinase - genetics; Glucokinase - metabolism; Glucose metabolism; Glucose Transporter Type 4 - genetics; Glucose Transporter Type 4 - metabolism; Glycogen Synthase Kinases - genetics; Glycogen Synthase Kinases - metabolism; Hyperglycemia - chemically induced; Hyperglycemia - drug therapy; Hyperglycemia - genetics; Hyperglycemia - pathology; Hypoglycemic Agents - pharmacology; Insulin; Insulin - blood; Insulin Receptor Substrate Proteins - genetics; Insulin Receptor Substrate Proteins - metabolism; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; MAPKs pathway; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Niacinamide; Piperazines - pharmacology; PPAR gamma - genetics; PPAR gamma - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; Signal Transduction; Streptozocin; Transcription Factor RelA - genetics; Transcription Factor RelA - metabolism; Type II diabetes mellitus; Glucose metabolism; MAPKs pathway; Type II diabetes mellitus; Eugenosedin-A; Insulin
• ISSN: 1607-551X; 2410-8650
• DOI: 10.1016/j.kjms.2017.11.003

This study examined the effects of eugenosedin-A (Eu-A) in a streptozotocin (STZ)/nicotinamide-induced rat model of type II diabetes mellitus (T2DM). Six-week-old Sprague–Dawley rats were randomly divided into three groups: (1) RD group, normal rats fed a regular diet (RD), (2) DM group, T2DM rats fed a high-fat diet, and (3) Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day). After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK) in liver and skeletal muscle and decreased protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), IRS-2, AMP-activated protein kinase (AMPK), glucose transporter-4 (GLUT-4), glucokinase (GCK), and peroxisome proliferator-activated receptor γ (PPAR-γ). STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK) and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.