Renal and vascular benefits of C-peptide: Molecular mechanisms of C-peptide action.
C-peptide has long been thought to be an inert byproduct of insulin production, but it has become apparent, and accepted, that C-peptide has important biological properties. C-peptide displays beneficial effects in many tissues affected by diabetic complications, such as increased peripheral blood flow and protection from renal damage. However, the mechanisms mediating these effects remain unclear. C-peptide interacts with cellular membranes at unidentified sites distinctive of the insulin family of receptors, and signals to multiple targets known to play a role in diabetes and diabetic complications, such as Na(+)/K(+)-ATPase and NOS. In general, the physiological and molecular effects of C-peptide resemble insulin, but C-peptide also possesses traits separate from those of insulin. These basic studies have been confirmed in human studies, suggesting that C-peptide may lend itself to clinical applications. However, the molecular and physiological properties of C-peptide are not completely elucidated, and large clinical studies have not begun. In order to further these goals, we critically summarize the current state of knowledge regarding C-peptide's renal and vascular effects and the molecular signaling of C-peptide.
Nordquist
Lina
L
Department of Medical Cell Biology, Division of Integrative Physiology, Uppsala University, Uppsala, Sweden;
Palm
Fredrik
F
Andresen
Bradley T
BT
Am J Physiol. 1993 May;264(5 Pt 2):R952-6
8388664
Curr Diab Rep. 2006 Aug;6(4):323-7
16879786
Farmaco Sci. 1973;28(4):316-22
4698887
N Engl J Med. 1993 Sep 30;329(14):977-86
8366922
Diabetes Metab Res Rev. 2006 Jul-Aug;22(4):313-22
16389646
Science. 1997 Jul 25;277(5325):563-6
9228006
J Am Soc Nephrol. 2000 Jul;11(7):1199-1207
10864575
Diabetes. 2005 May;54(5):1497-505
15855338
Diabetologia. 2005 Jan;48(1):187-97
15624099
Atherosclerosis. 2008 Dec;201(2):248-57
18294642
Transplantation. 2006 May 15;81(9):1274-7
16699454
Kidney Int. 2001 Oct;60(4):1258-65
11576340
J Am Soc Nephrol. 2003 Aug;14(8):2150-8
12874470
J Clin Invest. 2001 Jan;107(2):217-24
11160138
Cell Regul. 1991 Aug;2(8):675-84
1777507
Diabetologia. 2008 Jan;51(1):175-82
17965850
Diabetologia. 2003 Dec;46(12):1698-705
14586499
Kidney Int. 2003 Oct;64(4):1208-13
12969138
Science. 1995 Aug 4;269(5224):690-3
7624799
Diabetologia. 2005 Nov;48(11):2396-401
16195866
J Pept Res. 1999 Nov;54(5):408-14
10563506
J Clin Invest. 1993 Oct;92(4):1981-5
8408651
J Cell Sci. 2006 Aug 1;119(Pt 15):3021-3
16868029
Science. 1996 Jul 12;273(5272):245-8
8662509
Am J Physiol Endocrinol Metab. 2003 Oct;285(4):E864-70
12799312
Circ Res. 2006 Nov 24;99(11):1181-7
17068290
Acta Physiol (Oxf). 2007 Jul;190(3):253-9
17581137
Diabetologia. 1998 Mar;41(3):287-91
9541168
Methods Mol Biol. 2007;365:209-23
17200564
Kidney Int. 2005 Jan;67(1):295-300
15610255
Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R836-41
18077505
Biochem J. 2007 Dec 15;408(3):297-315
17850214
J Biol Chem. 1999 Jul 9;274(28):19992-20001
10391949
J Pharmacol Exp Ther. 2004 Nov;311(2):742-7
15231868
Biochemistry. 2004 Sep 21;43(37):11853-61
15362871
Cell Mol Life Sci. 2004 Nov;61(21):2782-90
15549182
Diabetologia. 1992 Feb;35(2):121-8
1547915
J Pharmacol Exp Ther. 2008 Jan;324(1):34-42
17911376
Science. 1997 Jan 17;275(5298):394-7
8994038
Diabetes Metab Res Rev. 2008 Feb;24(2):165-8
18157793
Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13318-23
10557318
J Am Soc Nephrol. 2006 Aug;17(8):2184-92
16807404
Drug News Perspect. 2005 Dec;18(10):639-43
16491166
Diabetologia. 1992 Dec;35(12):1151-8
1478367
Naunyn Schmiedebergs Arch Pharmacol. 2002 Jan;365(1):67-73
11862335
Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5297-301
8389480
Kidney Int. 1994 Sep;46(3):647-52
7527873
Diabet Med. 2000 Mar;17(3):181-9
10784221
Biochem J. 2001 Apr 1;355(Pt 1):123-9
11256956
Lancet. 1989 Mar 4;1(8636):461-3
2563840
Nature. 2001 Dec 13;414(6865):813-20
11742414
Trends Pharmacol Sci. 2005 Sep;26(9):470-6
16084602
Diabetes Care. 1996 Jun;19(6):564-8
8725852
Biochem J. 1993 Nov 15;296 ( Pt 1):15-9
8250835
Pulm Pharmacol Ther. 2007;20(6):734-9
17071121
J Physiol. 1996 Sep 15;495 ( Pt 3):597-609
8887769
Pflugers Arch. 2006 Jul;452(4):471-7
16523358
Diabetologia. 1996 Feb;39(2):199-205
8635672
J Biol Chem. 1996 Aug 9;271(32):19443-50
8702633
Exp Diabesity Res. 2004 Jan-Mar;5(1):91-6
15198374
Clin Physiol. 2001 Mar;21(2):164-71
11318824
Diabetes Metab Res Rev. 2003 Sep-Oct;19(5):375-85
12951645
FASEB J. 1999 Apr;13(6):685-94
10094929
Diabetes Care. 2005 Jun;28(6):1303-10
15920043
Acta Physiol Scand. 1996 Jan;156(1):19-25
8866882
Am J Physiol Heart Circ Physiol. 2000 Oct;279(4):H1453-9
11009429
Diabetologia. 2001 Oct;44(10):1247-57
11692173
Int J Pept Protein Res. 1988 Dec;32(6):419-24
3149951
Diabetes Care. 2005 Jun;28(6):1358-65
15920052
J Clin Invest. 1998 May 15;101(10):2036-41
9593759
J Biol Chem. 1985 Nov 25;260(27):14428-30
3863818
Acta Diabetol. 2007 Dec;44(4):215-8
17767370
J Biol Chem. 1996 May 24;271(21):12133-6
8647803
Diabetes Metab Res Rev. 2008 May-Jun;24(4):331-8
18088079
Biochem J. 2002 Sep 15;366(Pt 3):737-44
12059784
Nature. 1992 Dec 17;360(6405):686-9
1465134
Diabetologia. 2003 Jan;46(1):124-31
12637991
Nature. 1994 Jun 2;369(6479):418-20
8196770
Diabetes. 1994 Oct;43(10):1190-7
7926287
Kidney Int. 2005 May;67(5):2066; author reply 2066-7
15840062
Nephrol Dial Transplant. 2005 Mar;20(3):532-8
15665028
Am J Physiol. 1979 Aug;237(2):H118-24
464102
Proc Natl Acad Sci U S A. 1979 Dec;76(12):6270-3
293720
Diabetologia. 1998 Sep;41(9):1080-4
9754827
Transplantation. 2003 Apr 27;75(8):1296-301
12717219
Am J Physiol. 1999 Oct;277(4):G745-50
10516139
Am J Physiol. 1996 Dec;271(6 Pt 2):H2717-22
8997335
Nephrol Dial Transplant. 2004 Jun;19(6):1385-91
15004258
J Natl Med Assoc. 2005 Aug;97(8):1113-8
16173326
Mol Cell Biol. 1998 Feb;18(2):790-8
9447975
Diabetes Metab Res Rev. 2007 Jul;23(5):400-5
17103462
Gastroenterology. 1977 Apr;72(4 Pt.2):793-6
190081
Am J Physiol Renal Physiol. 2007 Feb;292(2):F804-11
17032938
Diabetes. 2002 Oct;51(10):3077-82
12351450
Kidney Int. 1993 Jun;43(6):1306-12
8315943
Biosci Rep. 1986 Feb;6(2):193-9
3013335
J Biochem. 2006 Jun;139(6):1083-8
16788059
J Biol Chem. 1982 Jun 25;257(12):7210-6
7200979
J Endocrinol. 1979 May;81(2):175-82
379261
Biochem J. 2006 May 15;396(1):193-200
16472257
Cell Mol Life Sci. 2007 Feb;64(4):479-86
17279313
Diabetologia. 1999 Apr;42(4):465-71
10230651
Acta Med Scand Suppl. 1975;578:59-68
239528
Cell Mol Life Sci. 2006 Dec;63(24):3055-60
17115117
Nitric Oxide. 2003 Sep;9(2):95-102
14623175
Urology. 2004 Sep;64(3):622-7
15351621
Am J Physiol. 1995 Dec;269(6 Pt 2):F876-83
8594883
J Am Soc Nephrol. 2006 Apr;17(4):986-95
16510765
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12706-10
7809106
Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H693-700
12689860