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A novel neuroprotective curcuminoid alleviates glucose intolerance and improves insulin signaling
Author(s) -
Panzhinskiy Evgeniy,
Lapchak Paul A,
Ren Jun,
Sreejayan Nair
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.672.7
Subject(s) - medicine , endocrinology , insulin receptor , insulin , type 2 diabetes , glucose transporter , neuroprotection , glucose uptake , glucose tolerance test , impaired glucose tolerance , insulin resistance , diabetes mellitus , chemistry , pharmacology
Type‐2 diabetes is growing at epidemic proportions and pharmacological interventions are being actively sought. This study examined the effect of a novel neuroprotective curcuminoid, CNB‐001 [4‐((1E)‐2‐(5‐(4‐hydroxy‐3‐methoxystyryl‐)‐1‐phenyl‐1H‐pyrazoyl‐3‐yl)vinyl)‐2‐methoxy‐phenol), on glucose intolerance and insulin signaling in high fat diet (HFD)‐fed mice. C57BL6 mice (5–6 week old) were randomly assigned to receive either a HFD (45% fat) or a low fat diet (LFD, 10% fat) for 24‐weeks, together with CNB‐001 (40mg/kg/d, ip). Glucose tolerance test revealed that that the area under the curve of post‐challenge glucose concentration was elevated on HF‐feeding, which was attenuated by CNB‐001. CNB‐001 attenuated body weight gain, serum triglycerides and IL‐6, augmented insulin signaling (elevated p‐Akt, p‐IRβ, lowered ER‐stress, PTP1B) and glucose uptake in gastrocnemius muscle of HFD‐fed mice. Respiratory quotient, measured using metabolic chamber, was elevated in HF‐fed mice, which was unaltered by CNB‐001, although CNB‐001 treatment resulted in higher energy expenditure. In cultured myotubes, CNB‐001 reversed palmitate‐induced impairment of insulin signaling and glucose‐uptake. Taken together, CNB‐001 alleviates obesity‐induced glucose intolerance and represents a potential candidate for further development as an antidiabetic agent. Supported by Wyoming INBRE (P20RR016474).