An extract of Artemisia dracunculus L. enhances insulin receptor signaling and modulates gene expression in skeletal muscle in KK-A(y) mice.
An ethanolic extract of Artemisia dracunculus L. (PMI 5011) has been observed to decrease glucose and insulin levels in animal models, but the cellular mechanisms by which insulin action is enhanced in vivo are not precisely known. In this study, we evaluated the effects of PMI 5011 to modulate gene expression and cellular signaling through the insulin receptor in skeletal muscle of KK-A(y) mice. Eighteen male KK-A(y) mice were randomized to a diet (w/w) mixed with PMI 5011 (1%) or diet alone for 8 weeks. Food intake, adiposity, glucose and insulin were assessed over the study, and at study completion, vastus lateralis muscle was obtained to assess insulin signaling parameters and gene expression. Animals randomized to PMI 5011 were shown to have enhanced insulin sensitivity and increased insulin receptor signaling, i.e., IRS-associated PI-3 kinase activity, Akt-1 activity and Akt phosphorylation, in skeletal muscle when compared to control animals (P<.01, P<.01 and P<.001, respectively). Gene expression for insulin signaling proteins, i.e., IRS-1, PI-3 kinase and Glut-4, was not increased, although a relative increase in protein abundance was noted with PMI 5011 treatment. Gene expression for specific ubiquitin proteins and specific 20S proteasome activity, in addition to skeletal muscle phosphatase activity, i.e., PTP1B activity, was significantly decreased in mice randomized to PMI 5011 relative to control. Thus, the data demonstrate that PMI 5011 increases insulin sensitivity and enhances insulin receptor signaling in an animal model of insulin resistance. PMI 5011 may modulate skeletal muscle protein degradation and phosphatase activity as a possible mode of action.
Wang
Zhong Q
ZQ
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
Ribnicky
David
D
Zhang
Xian H
XH
Zuberi
Aamir
A
Raskin
Ilya
I
Yu
Yongmei
Y
Cefalu
William T
WT
D000818:Animals; D019306:Artemisia / Q000737:chemistry*; D019587:Dietary Supplements; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000627:therapeutic use; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D008517:Phytotherapy; D010936:Plant Extracts / Q000378:metabolism / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D057149:Ubiquitinated Proteins / Q000235:genetics / Q000378:metabolism
D007004:Hypoglycemic Agents; C541449:PMI-5011; D010936:Plant Extracts; D012333:RNA, Messenger; D057149:Ubiquitinated Proteins; D011972:Receptor, Insulin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse; D046988:Proteasome Endopeptidase Complex
J Clin Invest. 1994 Mar;93(3):1156-62
8132755
Diabetes. 2009 Jul;58(7):1488-98
19336678
Phytochemistry. 2006 Jul;67(14):1539-46
16806328
Int J Cardiol. 2009 Jan 24;131(3):298-304
18684530
Metabolism. 2008 Jul;57(7 Suppl 1):S3-9
18555851
Phytomedicine. 2006 Sep;13(8):550-7
16920509
Phytother Res. 2010 Sep;24(9):1278-84
20175108
J Cell Physiol. 2000 Jan;182(1):1-11
10567911
Proc Nutr Soc. 1991 Dec;50(3):641-51
1809971
EMBO J. 1998 Dec 15;17(24):7151-60
9857172
Endocrinol Metab Clin North Am. 2005 Mar;34(1):77-98
15752923
Biochim Biophys Acta. 2005 Dec 30;1754(1-2):108-17
16198645
J Clin Endocrinol Metab. 2002 Jun;87(6):2474-80
12050202
Ann Med. 2006;38(1):64-80
16448990
Metabolism. 2008 Jul;57(7 Suppl 1):S58-64
18555856
Adv Exp Med Biol. 1988;246:7-15
3074669
Annu Rev Biochem. 1999;68:1015-68
10872471
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
9843981
Int J Pharm. 2009 Mar 31;370(1-2):87-92
19084584
Clin Chim Acta. 1977 Mar 15;75(3):387-91
856494
Metabolism. 2008 Jul;57(7 Suppl 1):S10-5
18555848
Diabet Med. 1997 Aug;14 Suppl 3:S12-8
9272608
Curr Drug Targets Immune Endocr Metabol Disord. 2001 Nov;1(3):265-75
12477292
J Clin Invest. 1997 Jul 15;100(2):449-58
9218523
Diabetologia. 1996 Oct;39(10):1208-14
8897009
Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1503-10
17848630
Bioinformatics. 2003 Jan 22;19(2):185-93
12538238
Diabetologia. 1985 Jul;28(7):412-9
3899825
Metabolism. 2008 Jul;57(7 Suppl 1):S1-2
18555847
J Nutr. 2006 Feb;136(2):415-20
16424121