Aegle marmelos impedes onset of insulin resistance syndrome in rats provided with drinking fructose from weaning to adulthood stages of development - a mechanistic study.
In this study, we explored the effect of aqueous extract of leaves of Aegle marmelos (AM) on hepatic carbohydrate metabolism and insulin downstream signalling in rats given fructose (15%) in drinking water from weaning to adulthood. Wistar albino rats (4 weeks old) were randomly divided into normal control (NC), fructose control (FC), and treatment (AMT) groups and were fed for a period of 8 weeks the following diets: chow + water, chow + fructose (15%), and chow + fructose (15%) + AM (500 mg/kg per day, p.o.), respectively. Compared with the NC group, the FC group was found to have significantly (p < 0.05) raised levels of fasting blood glucose, lipid, visceral mass, plasma insulin and leptin, glycogen, and gluconeogenesis enzyme but decreased glycolytic enzyme activity. Raised levels of glucose transporter 2 protein but decreased activity of phosphatidylinositol-3-kinase (PI3K/Akt) and Janus kinase - signal transducer and activator of transcription-3 (JAK-STAT3) in hepatic tissue indicate a state of insulin and leptin resistance in the FC group. A significant (p < 0.05) lowering of physical and glycemic parameters, strengthening of the hepatic glycolytic pathway over the gluconeogenic pathway, and upregulation of the PI3K/Akt and JAK-STAT3 pathways was observed in the AMT group, as compared with the FC group. For the first time, the mechanism underlying the development of insulin resistance syndrome is delineated here, along with the potential of A. marmelos to impede it.
a Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Pushp Vihar, Sec III, M.B. Road, New Delhi 110017, India.
Rajani
R
Mathur
a Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Pushp Vihar, Sec III, M.B. Road, New Delhi 110017, India.
Ratika
R
Sehgal
a Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Pushp Vihar, Sec III, M.B. Road, New Delhi 110017, India.
Preety
P
Rajora
a Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Pushp Vihar, Sec III, M.B. Road, New Delhi 110017, India.
Shveta
S
Sharma
a Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Pushp Vihar, Sec III, M.B. Road, New Delhi 110017, India.
Rajesh
R
Kumar
b Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Sandeep
S
Mathur
D045471:Aegle / Q000737:chemistry*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004326:Drinking; D005215:Fasting / Q000097:blood; D005632:Fructose / Q000008:administration & dosage*; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D048788:Growth and Development / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012431:Rutin / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D014886:Weaning
D001786:Blood Glucose; D051273:Glucose Transporter Type 2; D007328:Insulin; D020738:Leptin; D010936:Plant Extracts; D005632:Fructose; D012431:Rutin
Aegle marmelos; GLUT2 (« glucose transporter 2 »); JAK–STAT3; PI3K/Akt; fructose; gluconeogenesis; gluconéogenèse; glucose transporter 2 (GLUT2); insulin resistance syndrome; rutin; rutine; syndrome de résistance à l’insuline