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《Chinese Journal of Difficult and Complicated Cases》 2017-03
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Okra polysaccharide inhibiting hepatic gluconeogenesis by regulating PEPCK and AMPK in high fat diet mice

CHEN Lin;LU Ming;CAO Yuli;ZHANG Cuiping;LEI Tao;Department of Endocrinology,Putuo Hospital,Shanghai University of Traditional Chinese Medicine;  
Objective To observe the influence of okra polysaccharide(OP) on glucose levels,insulin resistance,and gluconeogenesis in high fat diet mice and to explore the possible mechanisms.Methods Forty CD47/BL male mice were divided into 4 groups(the OPL,OPH,S,and H groups).After 8 week high fat diet(HFD),the OPL,OPH,and S groups received low dose OP(150 mg·kg~(-1)· d~(-1)),high dose OP(300 mg·kg~(-1)·d~(-1)),and sitagliptin(10 mg·kg~(-1)·d~(-1))by daily gavage respectively.And the H group was simultaneously perfused with the same volume of saline.Glucose tolerance test(OGTT),pyruvic acid tolerance test(PTT),and insulin tolerance test(ITT) were undertaken after 10 weeks and the levels of PEPCK,G6 Pase,PGC 1α,KLF15 in liver were detected.Hepatic glycogen deposition was observed using periodic acid SchifF(PAS) staining.Results OGTT showed that OPL group had lower glucose levels at 60 minutes than H group[(17.71 ±4.05) mmol/L,(21.79 ±2.59) mmol/L,q =3.561,P =0.029)],and OPH group had decreased glucose levels at 30 and 60 minutes[(23.90 ±5.43) mmol/L,(16.43 ±4.42) mmol/L)]than H group[(29.07 ±3.38) mmol/L,(21.79 ±2.59) mmol/L,(q =3.204,P =0.036;q =3.792,P =0.015)].During PTT,OPL group had lower glucose levels at 15 and 30 minutes[(12.01 ±1.14) mmol/L,(14.18 ±1.46) mmol/L]than H group[(14.69 ± 1.68)mmol/L,16.82 ±2.74) mmol/L,(q = 5.668,P = 0.002;q = 3.623,P = 0.02)].And the glucose levels of OPH group went down at 15,30,and 60 minutes[(11.62 ± 1.98) mmol/L,(12.63 ±1.51) mmol/L,(11.59 ±1.97) mmol/L]compared with H group[(14.69±1.68) mmol/L,(16.82 ±2.74) mmol/L,(15.42 ±2.01)mmol/L,(q =5.281,P =0.002;q =5.978,P =0.001;g =5.930,P =0.004)].ITT expressed that OPH group had declined glucose levels at 60 and 90 minutest(4.35 ± 1.28) mmol/L,(5.83 ±1.03) mmol/L]than H group[(6.29 ±2.52) mmol/L,(8.48 ±1.92) mmol/L(q = 3.065,P =0.044;q =5.387,P =0.001)].Less expression of PEPCK,PGC lot,and KLF15 mRNA and unregulated level of AMPK mRNA in liver were found in OPH group(0.705 ± 0.172),(0.785 ± 0..123),(0.676 ± 0.080),(1.078 ±0.185) compared with those in H group[(1.013±0.249),(0.968 ±0.280),(0.904 ±0.192),(0.535±0.155)(q =4.304,P =0.008;q =3.295,P =0.033;q =4.617,P =0.013;q =3.175,P =0.039)].The protein levels of PGC 1α and KLF15 were significantly reduced in OPH and OPL groups than in H mice.OPH group had elevated hepatic glycogen deposition compared with Hgroup[(14.06 ±2.98,10.20±4.79)%(q =3.070,P =0.044)].Conclusion Our study suggests that okra polysaccharide ameliorates glucose metabolism and inhibits gluconeogenesis in insulin resistant mice.Downregulated PEPCK,PGC la,and KLF15 levels and increased AMPK expression were probably involved.
【Fund】: 上海市普陀区科委科研项目(15Q-05)
【CateGory Index】: R587.1
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