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Impaired microvascular insulin-dependent dilation in women with a history of gestational diabetes.
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- Additional Information
- Source:
Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901228 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1539 (Electronic) Linking ISSN: 03636135 NLM ISO Abbreviation: Am J Physiol Heart Circ Physiol Subsets: MEDLINE
- Publication Information:
Original Publication: Bethesda, Md. : American Physiological Society,
- Subject Terms:
- Abstract:
Women with a history of gestational diabetes mellitus (GDM) have a significantly greater lifetime risk of developing cardiovascular disease and type 2 diabetes compared with women who had an uncomplicated pregnancy (HC). Microvascular endothelial dysfunction, mediated via reduced nitric oxide (NO)-dependent dilation secondary to increases in oxidative stress, persists after pregnancy complicated by GDM. We examined whether this microvascular dysfunction reduces insulin-mediated vascular responses in women with a history of GDM. We assessed in vivo microvascular endothelium-dependent vasodilator function by measuring cutaneous vascular conductance responses to graded infusions of acetylcholine (10 -10 -10 -1 M) and insulin (10 -8 -10 -4 M) in control sites and sites treated with 15 mM l-NAME [ N G -nitro-l-arginine methyl ester; NO-synthase (NOS) inhibitor] or 5 mM l-ascorbate. We also measured protein expression of total endothelial NOS (eNOS), insulin-mediated eNOS phosphorylation, and endothelial nitrotyrosine in isolated endothelial cells from GDM and HC. Women with a history of GDM had reduced acetylcholine ( P < 0.001)- and insulin ( P < 0.001)-mediated dilation, and the NO-dependent responses to both acetylcholine ( P = 0.006) and insulin ( P = 0.006) were reduced in GDM compared with HC. Insulin stimulation increased phosphorylated eNOS content in HC ( P = 0.009) but had no effect in GDM ( P = 0.306). Ascorbate treatment increased acetylcholine ( P < 0.001)- and insulin ( P < 0.001)-mediated dilation in GDM, and endothelial cell nitrotyrosine expression was higher in GDM compared with HC ( P = 0.014). Women with a history of GDM have attenuated microvascular vasodilation responses to insulin, and this attenuation is mediated, in part, by reduced NO-dependent mechanisms. Our findings further implicate increased endothelial oxidative stress in this microvascular insulin resistance. NEW & NOTEWORTHY Women who have gestational diabetes during pregnancy are at a greater risk for cardiovascular disease and type 2 diabetes in the decade following pregnancy. The mechanisms mediating this increased risk are unclear. Herein, we demonstrate that insulin-dependent microvascular responses are reduced in women who had gestational diabetes, despite the remission of glucose intolerance. This reduced microvascular sensitivity to insulin may contribute to increased cardiovascular disease and type 2 diabetes risk in these women.
- Comments:
Comment in: Am J Physiol Heart Circ Physiol. 2024 Oct 1;327(4):H828-H829. doi: 10.1152/ajpheart.00572.2024. (PMID: 39178031)
- References:
J Appl Physiol (1985). 2008 Jul;105(1):370-2. (PMID: 17932300)
Am J Physiol Regul Integr Comp Physiol. 2012 Mar 15;302(6):R768-75. (PMID: 22204958)
J Vasc Res. 2010;47(1):1-8. (PMID: 19672102)
Microvasc Res. 2013 Jan;85:112-7. (PMID: 23137925)
Diabet Med. 2003 Apr;20(4):255-68. (PMID: 12675638)
Placenta. 2004 Jan;25(1):78-84. (PMID: 15013642)
J Appl Physiol (1985). 2022 Aug 1;133(2):361-370. (PMID: 35796611)
Diabetes Obes Metab. 2004 Nov;6(6):432-41. (PMID: 15479219)
Diabetes. 1999 Sep;48(9):1856-62. (PMID: 10480619)
Diabetes. 2002 May;51(5):1515-22. (PMID: 11978650)
J Appl Physiol (1985). 2003 Aug;95(2):504-10. (PMID: 12692141)
BMC Pregnancy Childbirth. 2019 Mar 29;19(1):107. (PMID: 30922259)
Circulation. 2004 Jun 1;109(21 Suppl 1):II27-33. (PMID: 15173060)
Am J Hypertens. 2010 May;23(5):541-6. (PMID: 20168305)
Atherosclerosis. 2013 Sep;230(1):131-9. (PMID: 23958265)
Sports Med. 2015 Feb;45(2):279-96. (PMID: 25281334)
Am J Physiol Endocrinol Metab. 2020 Nov 1;319(5):E923-E931. (PMID: 32954827)
Transl Res. 2018 Dec;202:83-98. (PMID: 30144425)
Clin Sci (Lond). 2008 Nov;115(9):295-300. (PMID: 18338981)
J Mol Cell Biol. 2021 Oct 21;13(7):500-512. (PMID: 33787922)
Hypertension. 2017 Aug;70(2):382-389. (PMID: 28652473)
Circulation. 2006 Apr 18;113(15):1888-904. (PMID: 16618833)
Diabetes Care. 1998 Dec;21(12):2111-5. (PMID: 9839102)
J Vasc Res. 2002 Jul-Aug;39(4):311-9. (PMID: 12187121)
Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):168-75. (PMID: 12588755)
Int J Microcirc Clin Exp. 1988 Nov;7(4):347-56. (PMID: 3220680)
Am J Physiol Regul Integr Comp Physiol. 2023 Mar 1;324(3):R293-R304. (PMID: 36622084)
Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1982-8. (PMID: 18772497)
Proc Soc Exp Biol Med. 1992 Jan;199(1):81-7. (PMID: 1728041)
Microcirculation. 2012 Aug;19(6):494-500. (PMID: 22360160)
Circulation. 2007 Feb 6;115(5):627-37. (PMID: 17242275)
Lancet. 2009 May 23;373(9677):1773-9. (PMID: 19465232)
Clin Biochem. 2004 Apr;37(4):293-8. (PMID: 15003731)
BMC Bioinformatics. 2006 Mar 09;7:123. (PMID: 16526949)
Heart. 2013 Aug;99(15):1118-21. (PMID: 23749791)
Microvasc Res. 2021 Mar;134:104104. (PMID: 33189732)
Vascul Pharmacol. 2012 Nov-Dec;57(5-6):139-49. (PMID: 22480621)
Eur J Pharmacol. 2010 Jun 25;636(1-3):8-17. (PMID: 20371238)
Circulation. 2012 Mar 20;125(11):1367-80. (PMID: 22344039)
Circ Res. 2017 Mar 3;120(5):784-798. (PMID: 27920123)
Vasc Health Risk Manag. 2008;4(5):1061-8. (PMID: 19183753)
J Hum Hypertens. 2012 Jan;26(1):56-63. (PMID: 21248780)
Cell Metab. 2010 May 5;11(5):379-89. (PMID: 20444418)
Cell Metab. 2011 Mar 2;13(3):294-307. (PMID: 21356519)
Nitric Oxide. 2002 Nov;7(3):149-64. (PMID: 12381413)
Microcirculation. 2014 Jul;21(5):380-7. (PMID: 24444138)
Circulation. 2011 Apr 12;123(14):1545-51. (PMID: 21444885)
Arterioscler Thromb Vasc Biol. 2012 Dec;32(12):3082-94. (PMID: 23042819)
Endocrinology. 1992 Jan;130(1):43-52. (PMID: 1727716)
J Hypertens. 2010 Feb;28(2):325-32. (PMID: 20051903)
J Vis Exp. 2014 Jun 16;(88):. (PMID: 24962357)
J Obstet Gynaecol Res. 2012 Aug;38(8):1057-63. (PMID: 22568764)
Diabetologia. 2019 Jun;62(6):905-914. (PMID: 30843102)
Circulation. 2004 Jun 1;109(21):2529-35. (PMID: 15136505)
Circulation. 2013 Jan 1;127(1):86-95. (PMID: 23204109)
Int J Endocrinol. 2016;2016:2070926. (PMID: 27956897)
Ann Med. 2015;47(7):615-23. (PMID: 26555575)
Br J Pharmacol. 2000 Jul;130(5):963-74. (PMID: 10882379)
Obstet Gynecol. 2018 Feb;131(2):e49-e64. (PMID: 29370047)
Arterioscler Thromb Vasc Biol. 2015 Apr;35(4):1022-9. (PMID: 25657309)
Biology (Basel). 2020 Dec 30;10(1):. (PMID: 33396868)
J Am Soc Nephrol. 2017 Mar;28(3):943-952. (PMID: 27620990)
Br J Pharmacol. 2017 Jun;174(12):1591-1619. (PMID: 27187006)
- Grant Information:
HL169201 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); UL1TR002537 HHS | NIH | National Center for Advancing Translational Sciences (NCATS); UL1 TR002537 United States TR NCATS NIH HHS; Fraternal Order of Eagles Diabetes Research Center; R01 HL169201 United States HL NHLBI NIH HHS
- Contributed Indexing:
Keywords: endothelial function; gestational diabetes; insulin resistance; microvascular; nitric oxide
- Accession Number:
0 (Insulin)
EC 1.14.13.39 (Nitric Oxide Synthase Type III)
31C4KY9ESH (Nitric Oxide)
N9YNS0M02X (Acetylcholine)
0 (Vasodilator Agents)
EC 1.14.13.39 (NOS3 protein, human)
3604-79-3 (3-nitrotyrosine)
42HK56048U (Tyrosine)
V55S2QJN2X (NG-Nitroarginine Methyl Ester)
- Publication Date:
Date Created: 20240726 Date Completed: 20240911 Latest Revision: 20241104
- Publication Date:
20241104
- Accession Number:
PMC11482287
- Accession Number:
10.1152/ajpheart.00223.2024
- Accession Number:
39058435
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