Peroxisome proliferator-activated receptor (PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M1" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
    
        
            <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FE" d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5&#xA;t0.5 -143.5h2q155 193 155 297q0 26 -12 47q-5 8 -5 15q0 16 12.5 27t29.5 11q21 0 34 -21t13 -55z" /></g>

        
    
</svg>), a ligand-dependent transcription factor, negatively modulates high glucose effects. We postulated that rosiglitazone (RSG), an activator of PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M2" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
    
        
            <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FE"/></g>

        
    
</svg> prevents the upregulation of vascular endothelial growth factor (VEGF) and collagen IV by mesangial cells exposed to high glucose. Primary cultured rat mesangial cells were growth-arrested in 5.6&#x2009;mM (NG) or 25&#x2009;mM D-glucose (HG) for up to 48&#x2009;hours. In HG, PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M3" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
    
        
            <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FE"/></g>

        
    
</svg> mRNA and protein were reduced within 3&#x2009;h, and enhanced ROS generation, expression of <svg     style="vertical-align:-3.27599pt;width:49.924999px;" id="M4" height="20.8375" version="1.1" viewBox="0 0 49.924999 20.8375" width="49.924999"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
    
        
            <g transform="matrix(.017,-0,0,-.017,.062,16.7)"><path id="x70" d="M169 380l92 53q26 16 49 16q80 0 128.5 -56t48.5 -133q0 -108 -72.5 -180.5t-176.5 -91.5q-38 1 -69 18v-131q0 -57 13 -70t71 -18v-27h-236v27q49 5 61 17t12 61v452q0 48 -9.5 58.5t-56.5 16.5v24q66 11 145 43v-79zM169 346v-270q37 -39 94 -39q63 0 101.5 50&#xA;t38.5 134q0 78 -38.5 123t-95.5 45q-45 0 -100 -43z" /></g><g transform="matrix(.017,-0,0,-.017,8.97,16.7)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g><g transform="matrix(.017,-0,0,-.017,17.129,16.7)"><use xlink:href="#x32"/></g>

            <g transform="matrix(.012,-0,0,-.012,25.287,8.537)"><use xlink:href="#x70"/></g><g transform="matrix(.012,-0,0,-.012,31.451,8.537)"><path id="x68" d="M513 0h-211v26q44 5 55 17t11 60v166q0 123 -98 123q-59 0 -104 -51v-238q0 -48 10 -60.5t55 -16.5v-26h-213l1 26q46 4 57 16t11 61v477q0 48 -9.5 58.5t-58.5 14.5v24q63 9 147 35v-336q73 73 143 73q64 0 101 -42t37 -129v-175q0 -49 11 -61t55 -16v-26z" /></g><g transform="matrix(.012,-0,0,-.012,37.757,8.537)"><path id="x6F" d="M257 449q92 0 154 -65t62 -158q0 -112 -67 -175t-150 -63q-98 0 -158.5 66.5t-60.5 154.5q0 59 21 106.5t54.5 75.5t71 43t73.5 15zM244 416q-48 0 -81 -47t-33 -128q0 -96 38 -158t99 -62q51 0 82 43.5t31 139.5q0 91 -36 151.5t-100 60.5z" /></g><g transform="matrix(.012,-0,0,-.012,43.635,8.537)"><path id="x78" d="M474 0h-214v26q32 4 39 12t-5 28l-74 117q-39 -58 -64 -106q-16 -25 -10 -35t44 -16v-26h-186v26q46 6 64 17t48 49t85 120l-87 136q-23 36 -40 47t-58 16v26h199v-26q-31 -4 -36.5 -12.5t9.5 -29.5l59 -93q37 56 58 94q13 23 7 30t-40 11v26h183v-26q-47 -5 -65 -13.5&#xA;t-45 -39.5q-24 -29 -78 -110l97 -148q28 -43 46.5 -55.5t63.5 -18.5v-26z" /></g>

        
    
</svg>, VEGF and collagen IV, and PKC-<svg     style="vertical-align:-2.55255pt;width:7.8249998px;" id="M5" height="15.95" version="1.1" viewBox="0 0 7.8249998 15.95" width="7.8249998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
    
        
            <g transform="matrix(.017,-0,0,-.017,.062,12.713)"><path id="x1D701" d="M430 689q0 -42 -40.5 -66t-86.5 -28q-79 -65 -137 -176t-58 -211q0 -52 21 -79t60 -41q25 -9 62 -18q77 -20 77 -89q0 -34 -22 -69.5t-42 -54.5t-50 -44l-22 23q60 63 60 111q0 45 -50 55q-42 8 -67 18q-55 20 -83.5 56t-28.5 105q0 113 68 224t164 194q-52 1 -86 23.5&#xA;t-34 51.5q0 20 21 40t53 30l17 -12q-13 -17 -13 -36t19 -38.5t58 -22.5q85 65 123 65q17 0 17 -11z" /></g>

        
    
</svg> membrane association were prevented by RSG. In NG, inhibition of PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M6" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
    
        
            <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FE"/></g>

        
    
</svg> caused ROS generation and VEGF expression that were unchanged by RSG. Reduced AMP-activated protein kinase (AMPK) phosphorylation in HG was unchanged with RSG, and VEGF expression was unaffected by AMPK inhibition. Hence, PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M7" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
    
        
            <g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FE"/></g>

        
    
</svg> is a negative modulator of HG-induced signaling that acts through PKC-<svg     style="vertical-align:-2.55255pt;width:7.8249998px;" id="M8" height="15.95" version="1.1" viewBox="0 0 7.8249998 15.95" width="7.8249998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
    
        
            <g transform="matrix(.017,-0,0,-.017,.062,12.713)"><use xlink:href="#x1D701"/></g>

        
    
</svg> but not AMPK and regulates VEGF and collagen IV expression by mesangial cells.

Catharine Whiteside

Hong Wang

Ling Xia

Snezana Munk

Howard J. Goldberg

I. George Fantus

Rosiglitazone Prevents High Glucose-Induced Vascular Endothelial Growth Factor and Collagen IV Expression in Cultured Mesangial Cells

<i  >Aims</i>. The glycosphingolipid <svg     style="vertical-align:-3.56265pt;width:10px;" id="M1" height="16.6625" version="1.1" viewBox="0 0 10 16.6625" width="10"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,12.162)"><path id="x1D6FD" d="M558 587q0 -32 -14 -61t-40 -53.5t-48.5 -41t-54.5 -36.5q144 -51 144 -174q0 -55 -43.5 -108t-104.5 -87q-77 -42 -131 -42q-31 0 -54 20t-31 47l11 18q48 -29 108 -29q79 0 119.5 43t40.5 109t-44.5 107.5t-119.5 50.5l22 47q34 1 65 21q96 61 96 157q0 42 -24 67.5&#xA;t-62 25.5q-24 0 -43.5 -9t-35 -29.5t-27 -44t-22.5 -63t-19.5 -75.5t-18.5 -91q-57 -294 -68 -380q-26 -190 -35 -200q-26 -31 -97 -37l-4 26q19 9 48 170l77 413q23 121 52.5 187.5t83.5 114.5q70 62 148 62q51 0 88.5 -34t37.5 -91z" /></g>

		
	
</svg>-galactosylceramide-3-<svg     style="vertical-align:-0.23206pt;width:13.175px;" id="M2" height="11.75" version="1.1" viewBox="0 0 13.175 11.75" width="13.175"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.4)"><path id="x1D442" d="M745 361q0 -166 -116 -272t-291 -106q-136 0 -225.5 83t-89.5 218q0 161 115.5 272t288.5 111q137 0 227.5 -83t90.5 -223zM643 359q0 126 -56 199.5t-167 73.5q-130 0 -213.5 -104t-83.5 -246q0 -117 58 -190.5t165 -73.5q91 0 160.5 52t103 128.5t33.5 160.5z" /></g>

		
	
</svg>-sulfate (sulfatide) is present in the secretory granules of the insulin producing <svg     style="vertical-align:-3.56265pt;width:10px;" id="M3" height="16.6625" version="1.1" viewBox="0 0 10 16.6625" width="10"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,12.162)"><use xlink:href="#x1D6FD"/></g>

		
	
</svg>-cells and may act as a molecular chaperone of insulin. The final step in sulfatide synthesis is performed by cerebroside sulfotransferase (CST) (EC 2.8.2.11). The aim of this study was to investigate whether two single nucleotide polymorphisms (SNP), rs2267161 located in an exon or rs42929 located in an intron, in the gene encoding CST are linked to type 2 diabetes (T2D). <i  >Methods</i>. As a population survey, 265 male and female patients suffering from T2D and 291 gender matched controls were examined.  <i  >Results</i>. A higher proportion of T2D patients were heterozygous at SNP rs2267161 with both T (methionine) and C (valine) alleles present (49.8&#x25; versus 41.3&#x25;, <svg     style="vertical-align:-0.1638pt;width:50.549999px;" id="M4" height="11.375" version="1.1" viewBox="0 0 50.549999 11.375" width="50.549999"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x1D443" d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5&#xA;t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" /></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><path id="x3D" d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" /></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><path id="x2E" d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" /></g><g transform="matrix(.017,-0,0,-.017,34.162,11.112)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" /></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><path id="x34" d="M456 178h-96v-72q0 -51 12.5 -62.5t72.5 -16.5v-27h-256v27q65 5 78 17t13 62v72h-260v28q182 271 300 426h40v-407h96v-47zM280 225v295h-2q-107 -148 -196 -295h198z" /></g>

		
	
</svg>). The calculated odd risk for T2D was 1.47 (1.01&#x2013;2.15, <svg     style="vertical-align:-0.1638pt;width:58.712502px;" id="M5" height="11.375" version="1.1" viewBox="0 0 58.712502 11.375" width="58.712502"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,34.162,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x34"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><path id="x37" d="M447 623l8 -12l-283 -613l-74 -10l-7 11q174 283 297 551h-216q-48 0 -62.5 -12t-33.5 -63h-29q10 60 18 148h382z" /></g>

		
	
</svg>). Among female controls, the homozygous CC individuals displayed lower insulin resistance measured by HOMA-IR (<svg     style="vertical-align:-0.1638pt;width:50.549999px;" id="M6" height="11.375" version="1.1" viewBox="0 0 50.549999 11.375" width="50.549999"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,34.162,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><path id="x35" d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8&#xA;l-26 -65h-233z" /></g>

		
	
</svg>) than the C/T or TT persons; this was particularly prevalent in individuals who exercise (<svg     style="vertical-align:-0.1638pt;width:50.549999px;" id="M7" height="11.375" version="1.1" viewBox="0 0 50.549999 11.375" width="50.549999"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,34.162,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><path id="x33" d="M285 378v-2q65 -13 102 -54.5t37 -97.5q0 -57 -30.5 -104.5t-74 -75t-85.5 -42t-72 -14.5q-31 0 -59.5 11t-40.5 23q-19 18 -16 36q1 16 23 33q13 10 24 0q58 -51 124 -51q55 0 88 40t33 112q0 64 -39 96.5t-88 32.5q-29 0 -64 -11l-6 29q77 25 118 57.5t41 84.5&#xA;q0 45 -26.5 69.5t-68.5 24.5q-67 0 -120 -79l-20 20l43 63q51 56 127 56h1q66 0 107 -37t41 -95q0 -42 -31 -71q-22 -23 -68 -54z" /></g>

		
	
</svg>). <i  >Conclusion</i>. Heterozygosity at SNP rs2267161 in the gene encoding the CST enzyme confers increased risk of T2D. Females with the CC allele showed lower insulin resistance.

A. Roeske-Nielsen

K. Buschard

J. E. Månson

L. Rastam

U. Lindblad

A Variation in the Cerebroside Sulfotransferase Gene Is Linked to Exercise-Modified Insulin Resistance and to Type 2 Diabetes

The purpose of this study was to determine whether AVE7688 a drug that inhibits both angiotensin converting enzyme and neutral endopeptidase activity protects vascular and nerve functions in an animal model of metabolic syndrome.  Obese Zucker rats at 20 weeks of age were treated for 12 weeks with AVE7688. Vasodilation in epineurial arterioles was measured by videomicroscopy and nerve conduction velocity was measured following electrical stimulation. Treatment with AVE7688 improved vascular relaxation in response to acetylcholine and motor and sensory nerve conduction velocity. In obese Zucker rats superoxide levels and nitrotyrosine staining were elevated in the aorta and treatment corrected both conditions. Obese Zucker rats were hypoalgesic in response to a thermal stimulus and demonstrated signs of impaired tactile response and both conditions were significantly improved with treatment. Even though obese Zucker rats are normoglycemic vascular and neural dysfunctions develop with age and can be improved by treatment with AVE7688.

Eric P. Davidson

Lawrence J. Coppey

Travis L. Kleinschmidt

Christine L. Oltman

Mark A. Yorek

Vascular and Neural Dysfunctions in Obese Zucker Rats: Effect of AVE7688

Positional cloning of lymphopenia (<i  >lyp</i>) in the BB rat revealed a frameshift mutation in <i  >Gimap5</i>, a member of at least seven related GTPase Immune Associated Protein genes located on rat chromosome 4q24.  Our aim was to clone and sequence the cDNA of the BB diabetes prone (DP) and diabetes resistant (DR) alleles of all seven <i  >Gimap</i> genes in the congenic DR.<i  >lyp</i> rat line with 2 Mb of BB DP DNA introgressed onto the DR genetic background.  All (100&#x25;)  <svg     style="vertical-align:-0.16379pt;width:66.712502px;" id="M1" height="16.9625" version="1.1" viewBox="0 0 66.712502 16.9625" width="66.712502"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,16.7)"><path id="x44" d="M43 650h280q194 0 282 -85q85 -82 85 -215q0 -173 -123 -267q-107 -83 -297 -83h-236v27q65 5 79.5 19.5t14.5 77.5v402q0 45 -6 62.5t-21.5 24t-57.5 9.5v28zM213 547v-416q0 -55 24.5 -75t81.5 -20q133 0 203 86t70 214q0 80 -30 143t-88 97q-66 41 -170 41&#xA;q-62 0 -78 -13q-13 -9 -13 -57z" /></g><g transform="matrix(.017,-0,0,-.017,12.404,16.7)"><path id="x52" d="M631 18l-4 -26q-24 0 -35 1q-57 3 -92.5 23t-69.5 68q-21 30 -101 160q-13 22 -30.5 31t-54.5 9h-32v-159q0 -63 14 -77.5t74 -19.5v-28h-262v28q62 5 76 19.5t14 77.5v402q0 62 -13 76t-73 19v28h248q109 0 159 -34q67 -42 67 -131q0 -115 -127 -172q27 -52 89 -144&#xA;q49 -71 81 -104q31 -36 72 -47zM212 316h48q73 0 108 29q55 42 55 124q0 76 -42 112t-104 36q-41 0 -54 -10q-11 -7 -11 -44v-247z" /></g><g transform="matrix(.017,-0,0,-.017,22.96,16.7)"><path id="x2E" d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" /></g>

			<g transform="matrix(.012,-0,0,-.012,26.838,8.537)"><path id="x1D459" d="M238 681l-124 -585q-7 -31 4 -31q10 0 37.5 18.5t49.5 41.5l16 -22q-40 -48 -89.5 -81.5t-76.5 -33.5q-42 0 -16 122l105 488q7 32 0 41t-39 9h-35l5 26q35 3 71 13t58 17.5t26 7.5q14 0 8 -31z" /></g><g transform="matrix(.012,-0,0,-.012,30.038,8.537)"><path id="x1D466" d="M556 393q0 -39 -36 -106q-42 -78 -185 -279q-47 -66 -81 -108t-117 -135l-112 -26l-8 22q150 90 251 219q-6 136 -39 340q-8 53 -21 53q-6 0 -27 -19.5t-38 -42.5l-16 26q80 111 127 111q23 0 35 -28t20 -90q18 -137 27 -263h2q142 200 142 279q0 24 -14 48q-4 7 5 26&#xA;q13 28 43 28q18 0 30 -15.5t12 -39.5z" /></g><g transform="matrix(.012,-0,0,-.012,36.928,8.537)"><path id="x1D45D" d="M570 304q0 -108 -87 -199q-40 -42 -94.5 -74t-105.5 -43q-41 0 -65 11l-29 -141q-9 -45 -1.5 -58t45.5 -16l26 -2l-5 -29l-241 -10l4 26q51 10 67.5 24t26.5 60l113 520q-54 -20 -89 -41l-7 26q38 28 105 53l11 49q20 25 77 58l8 -7l-17 -77q39 14 102 14q82 0 119 -36&#xA;t37 -108zM482 289q0 114 -113 114q-26 0 -66 -7l-70 -327q12 -14 32 -25t39 -11q59 0 118.5 81.5t59.5 174.5z" /></g>

			<g transform="matrix(.012,-0,0,-.012,43.988,8.537)"><path id="x2F" d="M368 703l-264 -866h-60l265 866h59z" /></g>

			<g transform="matrix(.012,-0,0,-.012,48.888,8.537)"><use xlink:href="#x1D459"/></g><g transform="matrix(.012,-0,0,-.012,52.088,8.537)"><use xlink:href="#x1D466"/></g><g transform="matrix(.012,-0,0,-.012,58.978,8.537)"><use xlink:href="#x1D45D"/></g>

		
	
</svg> rats are lymphopenic and develop type 1 diabetes (T1D) by 84 days of age while <svg     style="vertical-align:-0.16379pt;width:46.387501px;" id="M2" height="16.85" version="1.1" viewBox="0 0 46.387501 16.85" width="46.387501"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,16.588)"><use xlink:href="#x44"/></g><g transform="matrix(.017,-0,0,-.017,12.404,16.588)"><use xlink:href="#x52"/></g><g transform="matrix(.017,-0,0,-.017,22.96,16.588)"><use xlink:href="#x2E"/></g>

			<g transform="matrix(.012,-0,0,-.012,26.838,8.425)"><path id="x2B" d="M535 230h-212v-233h-58v233h-213v50h213v210h58v-210h212v-50z" /></g>

			<g transform="matrix(.012,-0,0,-.012,33.825,8.425)"><use xlink:href="#x2F"/></g>

			<g transform="matrix(.012,-0,0,-.012,38.725,8.425)"><use xlink:href="#x2B"/></g>

		
	
</svg> rats remain T1D and <i  >lyp</i> resistant.  Among the seven <i  >Gimap</i> genes, the <i  >Gimap5</i> frameshift mutation, a mutant allele that produces no protein, had the greatest impact on lymphopenia in the  <svg     style="vertical-align:-0.16379pt;width:66.712502px;" id="M3" height="16.9625" version="1.1" viewBox="0 0 66.712502 16.9625" width="66.712502"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,16.7)"><use xlink:href="#x44"/></g><g transform="matrix(.017,-0,0,-.017,12.404,16.7)"><use xlink:href="#x52"/></g><g transform="matrix(.017,-0,0,-.017,22.96,16.7)"><use xlink:href="#x2E"/></g>

			<g transform="matrix(.012,-0,0,-.012,26.838,8.537)"><use xlink:href="#x1D459"/></g><g transform="matrix(.012,-0,0,-.012,30.038,8.537)"><use xlink:href="#x1D466"/></g><g transform="matrix(.012,-0,0,-.012,36.928,8.537)"><use xlink:href="#x1D45D"/></g>

			<g transform="matrix(.012,-0,0,-.012,43.988,8.537)"><use xlink:href="#x2F"/></g>

			<g transform="matrix(.012,-0,0,-.012,48.888,8.537)"><use xlink:href="#x1D459"/></g><g transform="matrix(.012,-0,0,-.012,52.088,8.537)"><use xlink:href="#x1D466"/></g><g transform="matrix(.012,-0,0,-.012,58.978,8.537)"><use xlink:href="#x1D45D"/></g>

		
	
</svg> rat.  <i  >Gimap4</i> and <i  >Gimap1</i> each had one amino acid substitution of unlikely significance for lymphopenia.   Quantitative RT-PCR analysis showed a reduction in expression of all seven <i  >Gimap</i> genes in <svg     style="vertical-align:-0.16379pt;width:66.712502px;" id="M4" height="16.9625" version="1.1" viewBox="0 0 66.712502 16.9625" width="66.712502"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,16.7)"><use xlink:href="#x44"/></g><g transform="matrix(.017,-0,0,-.017,12.404,16.7)"><use xlink:href="#x52"/></g><g transform="matrix(.017,-0,0,-.017,22.96,16.7)"><use xlink:href="#x2E"/></g>

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			<g transform="matrix(.012,-0,0,-.012,43.988,8.537)"><use xlink:href="#x2F"/></g>

			<g transform="matrix(.012,-0,0,-.012,48.888,8.537)"><use xlink:href="#x1D459"/></g><g transform="matrix(.012,-0,0,-.012,52.088,8.537)"><use xlink:href="#x1D466"/></g><g transform="matrix(.012,-0,0,-.012,58.978,8.537)"><use xlink:href="#x1D45D"/></g>

		
	
</svg> spleen and mesenteric lymph nodes when compared to <svg     style="vertical-align:-0.16379pt;width:46.387501px;" id="M5" height="16.85" version="1.1" viewBox="0 0 46.387501 16.85" width="46.387501"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,16.588)"><use xlink:href="#x44"/></g><g transform="matrix(.017,-0,0,-.017,12.404,16.588)"><use xlink:href="#x52"/></g><g transform="matrix(.017,-0,0,-.017,22.96,16.588)"><use xlink:href="#x2E"/></g>

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			<g transform="matrix(.012,-0,0,-.012,38.725,8.425)"><use xlink:href="#x2B"/></g>

		
	
</svg>.  Only four; <i  >Gimap1</i>, <i  >Gimap4</i>, <i  >Gimap5</i>, and <i  >Gimap9</i> were reduced in thymus.  Our data substantiates the <i  >Gimap5</i> frameshift mutation as the primary defect with only limited contributions to lymphopenia from the remaining <i  >Gimap</i> genes.

Elizabeth A. Rutledge

Jessica M. Fuller

Brian Van Yserloo

Daniel H. Moralejo

Ruth A. Ettinger

Prashant Gaur

Jana L. Hoehna

Morgan R. Peterson

Richard Jensen

Anne E. Kwitek

Åke Lernmark

Sequence Variation and Expression of the <i>Gimap</i> Gene Family in the BB Rat

<i  >Purpose</i>. The objective of this study was to determine the efficacy of dietary supplementation with the metal chelators, trientine or citric acid, in preventing the development of cardiomyopathy in the Zucker diabetic rat. <i  >Hypothesis</i>. We hypothesized that dietary chelators would attenuate metal-catalyzed oxidative stress and damage in tissues and protect against pathological changes in ventricular structure and function in type II diabetes. <i  >Methods</i>. Animals (10 weeks old) included lean control (LC, <i  >fa/+</i>), untreated Zucker diabetic fatty (ZDF, <i  >fa/fa</i>), and ZDF rats treated with either trientine (triethylenetetramine) or citrate at 20&#x2009;mg/d in drinking water, starting when rats were frankly diabetic. Cardiac functional assessment was determined using a Millar pressure/volume catheter placed in the left ventricle at 32 weeks of age. <i  >Results</i>. End diastolic volume for the ZDF animals increased by 36&#x25; indicating LV dilatation (<svg     style="vertical-align:-0.1638pt;width:50.549999px;" id="M1" height="11.375" version="1.1" viewBox="0 0 50.549999 11.375" width="50.549999"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x1D443" d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5&#xA;t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" /></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><path id="x3C" d="M512 -3l-437 233v51l437 233v-58l-378 -200v-2l378 -199v-58z" /></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><path id="x2E" d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" /></g><g transform="matrix(.017,-0,0,-.017,34.162,11.112)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" /></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><path id="x35" d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8&#xA;l-26 -65h-233z" /></g>

		
	
</svg>) and was accompanied by a 30&#x25; increase in the end diastolic pressure (<svg     style="vertical-align:-0.546pt;width:50.549999px;" id="M2" height="11.85" version="1.1" viewBox="0 0 50.549999 11.85" width="50.549999"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.113)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.113)"><path id="x2264" d="M531 71l-474 214v50l474 215v-56l-416 -184l416 -183v-56zM531 -40h-474v50h474v-50z" /></g><g transform="matrix(.017,-0,0,-.017,30.286,11.113)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,34.162,11.113)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.113)"><use xlink:href="#x35"/></g>

		
	
</svg>). Both trientine and citric acid prevented the increases in EDV and EDP (<svg     style="vertical-align:-0.1638pt;width:50.549999px;" id="M3" height="11.375" version="1.1" viewBox="0 0 50.549999 11.375" width="50.549999"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3C"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,34.162,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x35"/></g>

		
	
</svg>). Ejection fraction and myocardial relaxation were also significantly improved with chelator treatment. <i  >Conclusion</i>. Dietary supplementation with trientine and citric acid significantly prevented structural and functional changes in the diabetic heart, supporting the merits of mild chelators for  prevention of cardiovascular disease in diabetes.

John W. Baynes

David B. Murray

The Metal Chelators, Trientine and Citrate, Inhibit the Development of Cardiac Pathology in the Zucker Diabetic Rat

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<p><em>Journal of Diabetes Research</em> publishes articles related to type 1 and type 2 diabetes. Topics include etiology, pathogenesis, management, and prevention of diabetes, as well as associated complications such as nephropathy.</p>


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<p>Chief Editor Dr Mark Yorek, from the University of Iowa, is currently researching vascular and neural disease related to obesity and diabetes. His active research studies focus on etiology, treatment and prevention of nerve damage.</p>


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Journal of Diabetes Research - Table of contents 2009

title

Journal of Diabetes Research publishes articles related to type 1 and type 2 diabetes. Topics include etiology, pathogenesis, management, and prevention of diabetes, as well as associated complications such as nephropathy.

Journal of Diabetes Research