PT  - JOURNAL ARTICLE
AU  - Evgeniy Panzhinskiy
AU  - Yinan Hua
AU  - Paul A. Lapchak
AU  - Elena Topchiy
AU  - Teresa E. Lehmann
AU  - Jun Ren
AU  - Sreejayan Nair
TI  - Novel Curcumin Derivative CNB-001 Mitigates Obesity-Associated Insulin Resistance
AID  - 10.1124/jpet.113.208728
DP  - 2014 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 248--257
VI  - 349
IP  - 2
4099  - http://jpet.aspetjournals.org/content/349/2/248.short
4100  - http://jpet.aspetjournals.org/content/349/2/248.full
SO  - J Pharmacol Exp Ther2014 May 01; 349
AB  - 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 weeks 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 (40 mg/kg i.p. per day). Glucose tolerance test revealed that the area under the curve of postchallenge glucose concentration was elevated on HF-feeding, which was attenuated by CNB-001. CNB-001 attenuated body weight gain, serum triglycerides, and IL-6, and augmented insulin signaling [elevated phosphoprotein kinase B (p-Akt), and phosphoinsulin receptor (p-IR)β, lowered endoplasmic reticulum (ER) stress, protein–tyrosine phosphatase 1B (PTP1B)] and glucose uptake in gastrocnemius muscle of HFD-fed mice. Respiratory quotient, measured using a metabolic chamber, was elevated in HFD-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. Docking studies suggest a potential interaction between CNB-001 and PTP1B. Taken together, CNB-001 alleviates obesity-induced glucose intolerance and represents a potential candidate for further development as an antidiabetic agent.