D-chiro-inositol glycans in insulin signaling and insulin resistance.
Classical actions of insulin involve increased glucose uptake from the bloodstream and its metabolism in peripheral tissues, the most important and relevant effects for human health. However, nonoxidative and oxidative glucose disposal by activation of glycogen synthase (GS) and mitochondrial pyruvate dehydrogenase (PDH) remain incompletely explained by current models for insulin action. Since the discovery of insulin receptor Tyr kinase activity about 25 years ago, the dominant paradigm for intracellular signaling by insulin invokes protein phosphorylation downstream of the receptor and its primary Tyr phosphorylated substrates-the insulin receptor substrate family of proteins. This scheme accounts for most, but not all, intracellular actions of insulin. Essentially forgotten is the previous literature and continuing work on second messengers generated in cells in response to insulin. Treatment and even prevention of diabetes and metabolic syndrome will benefit from a more complete elucidation of cellular-signaling events activated by insulin, to include the actions of second messengers such as glycan molecules that contain D-chiro-inositol (DCI). The metabolism of DCI is associated with insulin sensitivity and resistance, supporting the concept that second messengers have a role in responses to and resistance to insulin.
Larner
Joseph
J
Allomed Pharmaceuticals, Charlottesville, Virginia, United States of America. jl6d@virginia.edu
Brautigan
David L
DL
Thorner
Michael O
MO
D006006:Glycogen Synthase / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011134:Polysaccharides / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
D007328:Insulin; D011134:Polysaccharides; D011768:Pyruvate Dehydrogenase Complex; C068698:inositol-glycan; D007294:Inositol; D006006:Glycogen Synthase; D011972:Receptor, Insulin
Biochemistry. 1973 Nov 6;12(23):4507-12
4149348
J Biol Chem. 2009 Apr 3;284(14):9443-57
19188364
Proc Natl Acad Sci U S A. 1986 Aug;83(16):5793-7
3016721
Cold Spring Harb Symp Quant Biol. 1988;53 Pt 2:965-71
3076102
Biochem Biophys Res Commun. 1988 Mar 30;151(3):1416-26
2833261
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5924-8
8392181
Fed Proc. 1982 Sep;41(11):2730-5
6811328
J Biol Chem. 2008 Nov 28;283(48):33428-36
18768479
Biochem Soc Trans. 2009 Feb;37(Pt 1):217-22
19143635
J Biol Chem. 1992 Aug 25;267(24):16904-10
1387397
Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9988-92
8234346
J Clin Endocrinol Metab. 2006 Feb;91(2):709-17
16332940
FEBS Lett. 1999 Nov 12;461(1-2):120-4
10561508
Fed Proc. 1982 Sep;41(11):2724-9
6288476
Biochem J. 2005 Mar 1;386(Pt 2):237-44
15461583
Science. 1988 Apr 22;240(4851):509-11
3282305
J Clin Endocrinol Metab. 2004 Jan;89(1):242-9
14715857
Mol Cell Biol. 2000 Jul;20(13):4708-23
10848597
J Biol Chem. 1992 Feb 15;267(5):2864-7
1346611
Ann N Y Acad Sci. 1989;573:297-305
2517463
Diabetes Care. 2006 Feb;29(2):300-5
16443877
Biochim Biophys Acta. 1969 Apr 1;177(2):204-12
4305362
J Physiol. 2006 Jul 1;574(Pt 1):73-83
16709629
Yonsei Med J. 2005 Aug 31;46(4):532-8
16127779
J Biol Chem. 1980 Jul 25;255(14):6529-31
6993474
Science. 1979 Dec 21;206(4425):1407-8
505013
Biochem Biophys Res Commun. 1987 Jul 31;146(2):764-70
3304285
Am J Physiol Endocrinol Metab. 2002 Aug;283(2):E374-82
12110545
Biochem Biophys Res Commun. 1992 Apr 30;184(2):1042-7
1575723
Biochemistry. 2005 Aug 23;44(33):11067-73
16101290
Endocrinology. 1993 Feb;132(2):640-5
8425483
Eur J Biochem. 1981 Oct;119(3):503-10
6273162
Diabetes. 2007 Feb;56(2):414-23
17259386
Bioorg Med Chem. 2005 Dec 15;13(24):6732-41
16115771
N Engl J Med. 1990 Aug 9;323(6):373-8
2370888
Biochem Biophys Res Commun. 2002 May 10;293(3):1092-8
12051772
J Clin Invest. 1954 Mar;33(3):326-32
13143077
Bull Soc Chim Biol (Paris). 1967;49(4):415-31
6060514
Science. 1979 Dec 21;206(4425):1408-10
228395
Diabetologia. 1997 May;40(5):557-63
9165224
Bioorg Med Chem. 2010 Feb;18(3):1103-10
20079654
J Clin Endocrinol Metab. 1998 Jun;83(6):2001-5
9626131
Adv Second Messenger Phosphoprotein Res. 1990;24:290-4
2169809
Am J Clin Nutr. 2005 Feb;81(2):341-54
15699220
J Biol Chem. 1980 Aug 25;255(16):7540-3
6249805
Nat Cell Biol. 2002 Sep;4(9):648-57
12172553
Mol Cells. 1998 Jun 30;8(3):301-9
9666467
Endocrinology. 1993 Feb;132(2):652-7
8425485
Biochem Biophys Res Commun. 2002 Jul 12;295(2):561-9
12150987
Ann N Y Acad Sci. 1989;573:285-96
2699402
J Biol Chem. 2004 May 21;279(21):22715-26
15016818
J Biol Chem. 1991 Dec 15;266(35):23670-5
1748644
J Comp Neurol. 1998 Aug 31;398(3):323-32
9714146
J Med Chem. 2003 Jul 17;46(15):3283-91
12852758
J Biol Chem. 2010 Jan 22;285(4):2245-57
19897488
Metabolism. 1997 Nov;46(11):1270-4
9361684
Biochem J. 1991 Mar 1;274 ( Pt 2):369-74
2006906
Lancet. 1962 Dec 29;2(7270):1348-51
13982963
Diabetes Care. 1994 Dec;17(12):1465-8
7882818
Biochem J. 1996 Dec 15;320 ( Pt 3):801-6
9003365
J Biol Chem. 2002 Sep 20;277(38):35219-24
12133831
J Biol Chem. 1992 Aug 15;267(23):16266-73
1322896
Diabetes. 1993 May;42(5):643-50
8387037
Diabetes Care. 1996 Jan;19(1):76-8
8720541