Abstract
Dodeca-2(E),4(E)-dienoic acid isobutylamide (DDI), an alkamide derived from the plant Echinacea purpurea, promotes adipocyte differentiation and activates peroxisome proliferator-activated receptor γ, which is associated with enhanced insulin sensitivity. In the present study, we investigated whether DDI may increase glucose uptake through activation of the insulin signaling pathway in 3T3-L1 adipocytes. DDI increased insulin-stimulated glucose uptake, and expression and translocation of glucose transporter 4 in adipocytes treated with sub-optimal levels of insulin. Additionally, DDI enhanced Akt phosphorylation, whereas phosphoinositide 3-kinase/Akt inhibitors suppressed DDI-induced glucose uptake. These results suggest that DDI may improve insulin sensitivity through the activation of Akt signaling, which leads to enhanced glucose uptake.
Abbreviations
- DDI:
-
Dodeca-2(E),4(E)-dienoic acid isobutylamide
- IRS:
-
Insulin receptor substrate
- PI3K:
-
Phosphoinositide 3-kinase
- GLUT4:
-
Glucose transporter 4
- PPARγ:
-
Peroxisome proliferator-activated receptor γ
- DMEM:
-
Dulbecco’s Modified Eagle’s Medium
- BCS:
-
Bovine calf serum
- FBS:
-
Fetal bovine serum
- BSA:
-
Bovine serum albumin
- IBMX:
-
3-Isobutyl-1-methylxanthine
- PBS:
-
Phosphate-buffered saline
- KRH:
-
Krebs–Ringer Hepes
- SD:
-
Standard deviation
References
Lacquemant C, Vasseur F, Lepretre F, Froguel P (2003) Adipocytokins, obesity and development of type 2 diabetes. Med Sci 19:809–817. doi:10.1051/medsci/20031989809
Kahn BB, Flier JS (2000) Obesity and insulin resistance. J Clin Investig 106:473–481. doi:10.1172/JCI10842
Cignarelli A, Giorgino F, Vettor R (2013) Pharmacologic agents for type 2 diabetes therapy and regulation of adipogenesis. Arch Physiol Biochem 119:139–150. doi:10.3109/13813455.2013.796996
Floyd ZE, Stephens JM (2012) Controlling a master switch of adipocyte development and insulin sensitivity: covalent modifications of PPARγ. Biochim Biophys Acta 1822:1090–1095. doi:10.1016/j.bbadis.2012.03.014
Arner P (2003) The adipocyte in insulin resistance: key molecules and the impact of the thiazolidinediones. Trends Endocrinol Metab 14:137–145
Summers SA, Whiteman EL, Birnbaum MJ (2000) Insulin signaling in the adipocyte. Int J Obes Relat Metab Disord 24(Suppl 4):S67–S70
Lee J, Pilch PF (1994) The insulin receptor: structure, function, and signaling. Am J Physiol 266:C319–C334
Farese RV, Sajan MP, Standaert ML (2005) Insulin-sensitive protein kinases (atypical protein kinase C and protein kinase B/Akt): actions and defects in obesity and type II diabetes. Exp Biol Med 230:593–605
White MF, Kahn CR (1994) The insulin signaling system. J Biol Chem 269:1–4
Taha C, Klip A (1999) The insulin signaling pathway. J Membr Biol 169:1–12
Christensen KB, Petersen RK, Petersen S, Kristiansen K, Christensen LP (2009) Activation of PPARγ by metabolites from the flowers of purple coneflower (Echinacea purpurea). J Nat Prod 72:933–937. doi:10.1021/np900003a
Shin DM, Choi KM, Lee YS, Kim W, Shin KO, Oh S, Jung JC, Lee MK, Lee YM, Hong JT, Yun YP, Yoo HS (2014) Echinacea purpurea root extract enhances the adipocyte differentiation of 3T3-L1 cells. Arch Pharm Res 37:803–812. doi:10.1007/s12272-013-0251-y
Christensen KB, Minet A, Svenstrup H, Grevsen K, Zhang H, Schrader E, Rimbach G, Wein S, Wolffram S, Kristiansen K, Christensen LP (2009) Identification of plant extracts with potential antidiabetic properties: effect on human peroxisome proliferator-activated receptor (PPAR), adipocyte differentiation and insulin-stimulated glucose uptake. Phytother Res 23:1316–1325. doi:10.1002/ptr.2782
Kotowska D, El-Houri RB, Borkowski K, Petersen RK, Frette XC, Wolber G, Grevsen K, Christensen KB, Christensen LP, Kristiansen K (2014) Isomeric C12-alkamides from the roots of Echinacea purpurea improve basal and insulin-dependent glucose uptake in 3T3-L1 adipocytes. Planta Med 80:1712–1720. doi:10.1055/s-0034-1383252
Gotti R, Fiori J, Hudaib M, Cavrini V (2002) Separation of alkamides from Echinacea purpurea extracts by cyclodextrin-modified micellar electrokinetic chromatography. Electrophoresis 23:3084–3092. doi:10.1002/1522-2683(200209)23:17<3084:AID-ELPS3084>3.0.CO;2-0
Perry NB, Burgess EJ, Glennie VL (2001) Echinacea standardization: analytical methods for phenolic compounds and typical levels in medicinal species. J Agric Food Chem 49:1702–1706
Barnes J, Anderson LA, Gibbons S, Phillipson JD (2005) Echinacea species (Echinacea angustifolia (DC.) Hell., Echinacea pallida (Nutt.) Nutt., Echinacea purpurea (L.) Moench): a review of their chemistry, pharmacology and clinical properties. J Pharm Pharmacol 57:929–954. doi:10.1211/0022357056127
Ong KW, Hsu A, Tan BK (2012) Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes. PLoS ONE 7:e32718. doi:10.1371/journal.pone.0032718
Jin S, Chang C, Zhang L, Liu Y, Huang X, Chen Z (2015) Chlorogenic acid improves late diabetes through adiponectin receptor signaling pathways in db/db mice. PLoS ONE 10:e0120842. doi:10.1371/journal.pone.0120842
Jay MA, Ren J (2007) Peroxisome proliferator-activated receptor (PPAR) in metabolic syndrome and type 2 diabetes mellitus. Curr Diabetes Rev 3:33–39
Govers R (2014) Cellular regulation of glucose uptake by glucose transporter GLUT4. Adv Clin Chem 66:173–240
Choi SS, Cha BY, Iida K, Lee YS, Yonezawa T, Teruya T, Nagai K, Woo JT (2011) Artepillin C, as a PPARγ ligand, enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells. Biochem Pharmacol 81:925–933. doi:10.1016/j.bcp.2011.01.002
Choi SS, Cha BY, Iida K, Sato M, Lee YS, Teruya T, Yonezawa T, Nagai K, Woo JT (2011) Honokiol enhances adipocyte differentiation by potentiating insulin signaling in 3T3-L1 preadipocytes. J Nat Med 65:424–430. doi:10.1007/s11418-011-0512-3
Park HG, Bak EJ, Woo GH, Kim JM, Quan Z, Kim JM, Yoon HK, Cheon SH, Yoon G, Yoo YJ, Na Y, Cha JH (2012) Licochalcone E has an antidiabetic effect. J Nutr Biochem 23:759–767. doi:10.1016/j.jnutbio.2011.03.021
Khan AH, Pessin JE (2002) Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways. Diabetologia 45:1475–1483. doi:10.1007/s00125-002-0974-7
Watson RT, Kanzaki M, Pessin JE (2004) Regulated membrane trafficking of the insulin-responsive glucose transporter 4 in adipocytes. Endocr Rev 25:177–204
Yang J, Holman GD (1993) Comparison of GLUT4 and GLUT1 subcellular trafficking in basal and insulin-stimulated 3T3-L1 cells. J Biol Chem 268:4600–4603
Gnudi L, Tozzo E, Shepherd PR, Bliss JL, Kahn BB (1995) High level overexpression of glucose transporter-4 driven by an adipose-specific promoter is maintained in transgenic mice on a high fat diet, but does not prevent impaired glucose tolerance. Endocrinology 136:995–1002. doi:10.1210/endo.136.3.7867610
Cushman SW, Wardzala LJ (1980) Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. J Biol Chem 255:4758–4762
Kohn AD, Summers SA, Birnbaum MJ, Roth RA (1996) Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. J Biol Chem 271:31372–31378
Acknowledgements
This research was supported by the Ministry of Trade, Industry & Energy (MOTIE, 1415126993) through the fostering project of Osong Academy-Industry Convergence (BAIO), the National Research Foundation of Korea [NRF] grant funded by the Korea government (MSIP) (No. MRC, 2008-0062275) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MOE) (No. 2015R1D1A1A01060790).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
The authors have no conflicts of interest to declare.
Rights and permissions
About this article
Cite this article
Choi, KM., Kim, W., Hong, J.T. et al. Dodeca-2(E),4(E)-dienoic acid isobutylamide enhances glucose uptake in 3T3-L1 cells via activation of Akt signaling. Mol Cell Biochem 426, 9–15 (2017). https://doi.org/10.1007/s11010-016-2876-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-016-2876-x