title: Upregulation of PPARγ by Aegle marmelos ameliorates insulin resistance and β-cell dysfunction in high fat diet fed-streptozotocin induced type 2 diabetic rats.
abstract: The global epidemic of type 2 diabetes demands the rapid evaluation of new and accessible interventions. This study investigated whether Aegle marmelos fruit aqueous extract (AMF; 250, 500 and 1000 mg/kg) improves insulin resistance, dyslipidemia and β-cell dysfunction in high fat diet fed-streptozotocin (HFD-STZ)-induced diabetic rats by modulating peroxisome proliferator-activated receptor-γ (PPARγ) expression. The serum levels of glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-B), lipid profile, TNF-α and IL-6 were evaluated. Further, the TBARS level and SOD activity in pancreatic tissue and PPARγ protein expression in liver were assessed. In addition, histopathological and ultrastructural studies were performed to validate the effect of AMF on β-cells. The HFD-STZ treated rats showed a significant increase in the serum levels of glucose, insulin, HOMA-IR, TNF-α, IL-6, dyslipidemia with a concomitant decrease in HOMA-B and PPARγ expression. Treatment with AMF for 21 days in diabetic rats positively modulated the altered parameters in a dose-dependent manner. Furthermore, AMF prevented inflammatory changes and β-cell damage along with a reduction in mitochondrial and endoplasmic reticulum swelling. These findings suggest that the protective effect of AMF in type 2 diabetic rats is due to the preservation of β-cell function and insulin-sensitivity through increased PPARγ expression.
authors.affiliation: Cardiovascular and Diabetes Research Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Sharma
authors.forename: Saurabh
authors.initials: S
authors.lastname: Bharti
authors.forename: Sameer
authors.initials: S
authors.lastname: Goyal
authors.forename: Sachin
authors.initials: S
authors.lastname: Arora
authors.forename: Saroj
authors.initials: S
authors.lastname: Nepal
authors.forename: Kamal
authors.initials: K
authors.lastname: Kishore
authors.forename: Sujata
authors.initials: S
authors.lastname: Joshi
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumari
authors.forename: Dharamvir Singh
authors.initials: DS
authors.lastname: Arya
mesh_terms: D045471:Aegle; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D048909:Diabetes Complications / Q000097:blood / Q000188:drug therapy; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology; D005260:Female; D005638:Fruit; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D015850:Interleukin-6; D047495:PPAR gamma; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha