Insulin-Mimetic Action of Vanadate: Role of Intracellular Magnesium

The insulin-mimetic effect of vanadate is well established, and vanadate has been shown to improve insulin sensitivity in diabetic rats and humans. Although the exact mechanism(s) remain undefined, we have previously demonstrated a direct relation of intracellular free magnesium (Mgi) levels to gluc...

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Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2001-09, Vol.38 (3, Part 2 Suppl), p.701-704
Main Authors: Barbagallo, Mario, Dominguez, Ligia J, Resnick, Lawrence M
Format: Article
Language:English
Subjects:
Apud cells. Peptide and protein hormones. Growth factors
Biological and medical sciences
Dose-Response Relationship, Drug
Erythrocytes - cytology
Erythrocytes - drug effects
Erythrocytes - metabolism
Female
Fundamental and applied biological sciences. Psychology
Humans
Hypertension - blood
Insulin - pharmacology
Magnesium - blood
Magnetic Resonance Spectroscopy
Male
Time Factors
Vanadates - pharmacology
Vertebrates: endocrinology
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container_end_page 704
container_issue 3, Part 2 Suppl
container_start_page 701
container_title Hypertension (Dallas, Tex. 1979)
container_volume 38
creator Barbagallo, Mario
Dominguez, Ligia J
Resnick, Lawrence M
description The insulin-mimetic effect of vanadate is well established, and vanadate has been shown to improve insulin sensitivity in diabetic rats and humans. Although the exact mechanism(s) remain undefined, we have previously demonstrated a direct relation of intracellular free magnesium (Mgi) levels to glucose disposal, to insulinemic responses following glucose loading, and to insulin-induced ionic effects. To investigate whether the insulin-mimetic effects of vanadate could similarly be mediated by Mgi, we utilized P-nuclear magnetic resonance spectroscopy to measure Mgi in erythrocytes from normal (NL, n=10) and hypertensive (HTN, n=12) subjects, before and after incubation with insulin and with different doses of sodium vanadate. In NL, vanadate elevated Mgi levels, with maximum efficacy at 50 7mgr;mol/L (186±6 to 222±6 7mgr;mol/L, P >0.01), as did physiologically maximal doses of insulin, 200 7mgr;U/mL (185±6 to 222±8 7mgr;mol/L, P
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Although the exact mechanism(s) remain undefined, we have previously demonstrated a direct relation of intracellular free magnesium (Mgi) levels to glucose disposal, to insulinemic responses following glucose loading, and to insulin-induced ionic effects. To investigate whether the insulin-mimetic effects of vanadate could similarly be mediated by Mgi, we utilized P-nuclear magnetic resonance spectroscopy to measure Mgi in erythrocytes from normal (NL, n=10) and hypertensive (HTN, n=12) subjects, before and after incubation with insulin and with different doses of sodium vanadate. In NL, vanadate elevated Mgi levels, with maximum efficacy at 50 7mgr;mol/L (186±6 to 222±6 7mgr;mol/L, P &gt;0.01), as did physiologically maximal doses of insulin, 200 7mgr;U/mL (185±6 to 222±8 7mgr;mol/L, P &lt;0.01). In HTN, only vanadate, but not insulin, increased Mgi (insulin173±7 to 180±9 7mgr;mol/L, P =NS; vanadate170±7 to 208±10 7mgr;mol/L, P &lt;0.01). Mgi responses to insulin (r =0.637, P &lt;0.001), but not to vanadate (r =0.15, P =NS), were closely and directly related to basal Mgi levels. We conclude that (1) both vanadate and insulin stimulate erythrocyte Mgi levels; (2) cellular Mgi responses to insulin, but not to vanadate, depend on basal Mgi content—the lower the basal Mgi, the less the Mgi response to insulin. As such, (3) Mgi responses to vanadate were equivalent among HTN and NL, whereas HTN cells exhibited blunted Mgi responses to insulin, and (4) the ability of vanadate to improve insulin sensitivity clinically may be mediated, at least in part, by its ability to increase Mgi levels, which in turn, helps to determine cellular insulin action.</description><identifier>ISSN: 0194-911X</identifier><identifier>EISSN: 1524-4563</identifier><identifier>DOI: 10.1161/hy09t1.095392</identifier><identifier>PMID: 11566960</identifier><identifier>CODEN: HPRTDN</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Apud cells. Peptide and protein hormones. Growth factors ; Biological and medical sciences ; Dose-Response Relationship, Drug ; Erythrocytes - cytology ; Erythrocytes - drug effects ; Erythrocytes - metabolism ; Female ; Fundamental and applied biological sciences. 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Although the exact mechanism(s) remain undefined, we have previously demonstrated a direct relation of intracellular free magnesium (Mgi) levels to glucose disposal, to insulinemic responses following glucose loading, and to insulin-induced ionic effects. To investigate whether the insulin-mimetic effects of vanadate could similarly be mediated by Mgi, we utilized P-nuclear magnetic resonance spectroscopy to measure Mgi in erythrocytes from normal (NL, n=10) and hypertensive (HTN, n=12) subjects, before and after incubation with insulin and with different doses of sodium vanadate. In NL, vanadate elevated Mgi levels, with maximum efficacy at 50 7mgr;mol/L (186±6 to 222±6 7mgr;mol/L, P &gt;0.01), as did physiologically maximal doses of insulin, 200 7mgr;U/mL (185±6 to 222±8 7mgr;mol/L, P &lt;0.01). In HTN, only vanadate, but not insulin, increased Mgi (insulin173±7 to 180±9 7mgr;mol/L, P =NS; vanadate170±7 to 208±10 7mgr;mol/L, P &lt;0.01). Mgi responses to insulin (r =0.637, P &lt;0.001), but not to vanadate (r =0.15, P =NS), were closely and directly related to basal Mgi levels. We conclude that (1) both vanadate and insulin stimulate erythrocyte Mgi levels; (2) cellular Mgi responses to insulin, but not to vanadate, depend on basal Mgi content—the lower the basal Mgi, the less the Mgi response to insulin. As such, (3) Mgi responses to vanadate were equivalent among HTN and NL, whereas HTN cells exhibited blunted Mgi responses to insulin, and (4) the ability of vanadate to improve insulin sensitivity clinically may be mediated, at least in part, by its ability to increase Mgi levels, which in turn, helps to determine cellular insulin action.</description><subject>Apud cells. Peptide and protein hormones. 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Psychology</topic><topic>Humans</topic><topic>Hypertension - blood</topic><topic>Insulin - pharmacology</topic><topic>Magnesium - blood</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Time Factors</topic><topic>Vanadates - pharmacology</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barbagallo, Mario</creatorcontrib><creatorcontrib>Dominguez, Ligia J</creatorcontrib><creatorcontrib>Resnick, Lawrence M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barbagallo, Mario</au><au>Dominguez, Ligia J</au><au>Resnick, Lawrence M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Insulin-Mimetic Action of Vanadate: Role of Intracellular Magnesium</atitle><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle><addtitle>Hypertension</addtitle><date>2001-09</date><risdate>2001</risdate><volume>38</volume><issue>3, Part 2 Suppl</issue><spage>701</spage><epage>704</epage><pages>701-704</pages><issn>0194-911X</issn><eissn>1524-4563</eissn><coden>HPRTDN</coden><abstract>The insulin-mimetic effect of vanadate is well established, and vanadate has been shown to improve insulin sensitivity in diabetic rats and humans. Although the exact mechanism(s) remain undefined, we have previously demonstrated a direct relation of intracellular free magnesium (Mgi) levels to glucose disposal, to insulinemic responses following glucose loading, and to insulin-induced ionic effects. To investigate whether the insulin-mimetic effects of vanadate could similarly be mediated by Mgi, we utilized P-nuclear magnetic resonance spectroscopy to measure Mgi in erythrocytes from normal (NL, n=10) and hypertensive (HTN, n=12) subjects, before and after incubation with insulin and with different doses of sodium vanadate. In NL, vanadate elevated Mgi levels, with maximum efficacy at 50 7mgr;mol/L (186±6 to 222±6 7mgr;mol/L, P &gt;0.01), as did physiologically maximal doses of insulin, 200 7mgr;U/mL (185±6 to 222±8 7mgr;mol/L, P &lt;0.01). In HTN, only vanadate, but not insulin, increased Mgi (insulin173±7 to 180±9 7mgr;mol/L, P =NS; vanadate170±7 to 208±10 7mgr;mol/L, P &lt;0.01). Mgi responses to insulin (r =0.637, P &lt;0.001), but not to vanadate (r =0.15, P =NS), were closely and directly related to basal Mgi levels. We conclude that (1) both vanadate and insulin stimulate erythrocyte Mgi levels; (2) cellular Mgi responses to insulin, but not to vanadate, depend on basal Mgi content—the lower the basal Mgi, the less the Mgi response to insulin. As such, (3) Mgi responses to vanadate were equivalent among HTN and NL, whereas HTN cells exhibited blunted Mgi responses to insulin, and (4) the ability of vanadate to improve insulin sensitivity clinically may be mediated, at least in part, by its ability to increase Mgi levels, which in turn, helps to determine cellular insulin action.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>11566960</pmid><doi>10.1161/hy09t1.095392</doi><tpages>4</tpages></addata></record>
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ispartof Hypertension (Dallas, Tex. 1979), 2001-09, Vol.38 (3, Part 2 Suppl), p.701-704
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1524-4563
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subjects Apud cells. Peptide and protein hormones. Growth factors
Biological and medical sciences
Dose-Response Relationship, Drug
Erythrocytes - cytology
Erythrocytes - drug effects
Erythrocytes - metabolism
Female
Fundamental and applied biological sciences. Psychology
Humans
Hypertension - blood
Insulin - pharmacology
Magnesium - blood
Magnetic Resonance Spectroscopy
Male
Time Factors
Vanadates - pharmacology
Vertebrates: endocrinology
title Insulin-Mimetic Action of Vanadate: Role of Intracellular Magnesium
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