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Fig. 5 | Nutrition & Metabolism

Fig. 5

From: Hsp90β knockdown in DIO mice reverses insulin resistance and improves glucose tolerance

Fig. 5

Anti-sense oligonucleotide (ASO) mediated Hsp90ab1 knockdown improves glucose tolerance and lowers levels of fed insulin and glucose in DIO mice. a Male mice were fed a high fat diet (DIO) for 12 weeks prior to receiving either negative control (NC) ASO or Hsp90ab1 ASO 10μg/kg/day two times a week for 4 weeks. Mice were then sacrificed, skeletal muscles were collected, and quantitative real time PCR was performed for mRNA expression of Hsp90ab1, Hsp90aa1, Hsp90b1 and TRAP1 and normalized to 18 s. ASO treatment decreases Hsp90ab1 mRNA expression (*p < 0.05). There is no effect upon the mRNA expression of Hsp90aa1, Hsp90b1 and TRAP1. Data represent mean + SEM of n = 10/group. b Body weight of DIO mice treated with NC or Hsp90ab1 ASO. c Bar graph of fed insulin levels after 4 weeks of ASO treatment in DIO mice shows a decrease in Hsp90ab1 treated mice. d Bar graph of fed glucose levels after 4 weeks of ASO treatment in DIO mice. DIO mice treated with Hsp90ab1 ASO show significant improvement in glucose tolerance. e Blood glucose levels measured over time during an intraperitoneal glucose tolerance test (IPGTT) in lean control mice and DIO mice administered either NC ASO (n = 10) or Hsp90ab1 ASO (n = 10) after fasting for 6 h. Blood glucose was measured periodically over a time course of 120 min. Hsp90ab1 knockdown decreased blood glucose at 60 and 90 min over untreated DIO mice (**p < 0.01, n = 5). f Area under the curve (AUC) analysis of IPGTT results from data in (e) shows a significant overall decrease in blood glucose in Hsp90ab1-knockdown mice (*p < 0.05). g Glycogen levels from skeletal muscles (gastrocnemius) of DIO mice after 4 weeks of ASO treatment. DIO mice treated with Hsp90ab1 ASO show increased glycogen levels compared to mice treated with NC (**p < 0.01, n = 8 per group). (g)

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