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DOI: 10.1055/s-0032-1330016
d-chiro-Inositol Attenuates Epinephrine-stimulated Hepatic Glucose Output in the Isolated Perfused Liver Independently of Insulin
Publikationsverlauf
received 30. Juli 2012
accepted 29. Oktober 2012
Publikationsdatum:
07. Dezember 2012 (online)
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Abstract
d-chiro-Inositol (DCI) is a cyclic sugar alcohol that evokes both antidiabetic and insulin sensitizing effects. Pharmacological administration of DCI has been shown to lower blood glucose in rat models of diabetes mellitus and enhance insulin sensitivity in humans with polycystic ovary syndrome (PCOS). We hypothesised that the antidiabetic effects of DCI could be due to inhibition of hepatic glucose output (HGO). To test this hypothesis, we perfused isolated rat livers either with buffer, myo-inositol, DCI, or insulin, and investigated their respective effects on the stimulation of HGO by epinephrine. We found that perfusion with 200 μM DCI attenuated epinephrine-stimulated HGO by 35% over 30 min as compared to the buffer control perfusion (p=0.05). By comparison, perfusion with 1 nM insulin attenuated epinephrine-stimulated HGO by 57% (p<0.0001). The glucose-lowering effects by DCI occurred independently of insulin and were specific to the DCI stereoisomer as 200 μM myo-inositol had no effect. These findings suggest that DCI could evoke its antidiabetic effects in vivo by inhibition of HGO. Further identification of the protein targets involved could open up new avenues to regulate hyperglycaemia with wider implications for the treatment of hepatic insulin resistance in PCOS.
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References
- 1 Larner J, Brautigan DL, Thorner MO. Mol Med 2010; 16: 543-552
- 2 Fonteles MC, Almeida MQ, Larner J. Horm Metab Res 2000; 32: 129-132
- 3 Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G. N Engl J Med 1999; 340: 1314-1320
- 4 Kennington AS, Hill CR, Craig J, Bogardus C, Raz I, Ortmeyer HK, Hansen BC, Romero G, Larner J.. N Engl J Med 1990; 323: 373-378
- 5 Asplin I, Galasko G, Larner J. Proc Natl Acad Sci USA 1993; 90: 5924-5928
- 6 Ostlund Jr RE, McGill JB, Herskowitz I, Kipnis DM, Santiago JV, Sherman WR. Proc Natl Acad Sci USA 1993; 90: 9988-9992
- 7 Baillargeon JP, Diamanti-Kandarakis E, Ostlund Jr RE, Apridonidze T, Iuorno MJ, Nestler JE. Diabetes Care 2006; 29: 300-305
- 8 Nascimento NR, Lessa LM, Kerntopf MR, Sousa CM, Alves RS, Queiroz MG, Price J, Heimark DB, Larner J, Du X, Brownlee M, Gow A, Davis C, Fonteles MC. Proc Natl Acad Sci USA 2006; 103: 218-223
- 9 Farias VX, Macedo FH, Oquendo MB, Tome AR, Bao SN, Cintra DO, Santos CF, Albuquerque AA, Heimark DB, Larner J, Fonteles MC, Leal-Cardoso JH, Nascimento NR. Diabetes Obes Metab 2011; 13: 243-250
- 10 Leonard BL, Watson RN, Loomes KM, Phillips AR, Cooper GJ. Acta Diabetol 2005; 42: 162-170
- 11 Home PD, Pacini G. Diabetes Obes Metab 2008; 10: 699-718
- 12 Englisch R, Wurzinger R, Furnsinn C, Schneider B, Frisch H, Waldhausl W, Graf J, Roden M. Biochem J 2000; 351: 39-45
- 13 Lin X, Ma L, Gopalan C, Ostlund RE. Brit J Nut 2009; 102: 1426-1434
- 14 Kawa JM, Przybylski R, Taylor CG. Exp Biol Med (Maywood) 2003; 228: 907-914