Artemether Alleviates Diabetic Kidney Disease by Modulating Amino Acid Metabolism

<div>Heatmaps and OPLS-DA of amino acid metabolites in T1DM and T2DM mice. Hierarchical clustering heatmaps of metabolites in T1DM (a) and T2DM (d) mice. (b) OPLS-DA score plot of T1D-ctrl and STZ group (validated by permutation tests, <span class="nowrap"><svg height="11.7978pt" id="M37" style="vertical-align:-0.2063999pt" version="1.1" viewbox="-0.0498162 -11.5914 58.424 11.7978" width="58.424pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M610 18C585 26 567 34 540 68C517 97 499 128 476 171C452 215 425 276 413 304C496 332 570 394 570 494C570 555 545 595 509 619S419 650 364 650H139L133 622C216 615 219 612 203 527L129 132C112 40 105 36 23 28L17 0H279L285 28C199 34 194 40 211 132L239 284H284C320 284 334 275 351 236C374 182 394 140 420 93C459 23 495 -1 592 -8H600L610 18ZM480 485C480 424 449 372 403 342C374 323 338 316 293 316H245L291 562C296 589 301 601 311 608S337 618 358 618C432 618 480 575 480 485Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,8.151,-5.741)"><path d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z"></path></g><g transform="matrix(.013,0,0,-0.013,13.098,0)"><path d="M640 650H413L406 622L438 617C475 611 483 605 463 571C422 503 346 400 296 333C264 403 215 529 199 575C189 604 191 614 228 618L262 622L271 650H30L23 622C90 615 97 609 119 553L212 321C222 295 223 285 218 259L193 127C176 39 167 33 82 28L76 0H350L356 28C266 36 257 40 275 127L303 266C308 290 314 302 328 322C396 418 454 493 498 546C551 610 565 616 631 622L640 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,25.211,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,36.474,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,42.714,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,45.678,0)"><path d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,51.919,0)"><path d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"></path></g></svg>,</span> <span class="nowrap"><svg height="13.7421pt" id="M38" style="vertical-align:-2.1507pt" version="1.1" viewbox="-0.0498162 -11.5914 57.4193 13.7421" width="57.4193pt" xmlns="http://www.w3.org/2000/svg" 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443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,35.467,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,38.431,0)"><path d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"></path></g><g transform="matrix(.013,0,0,-0.013,44.674,0)"><path d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"></path></g><g transform="matrix(.013,0,0,-0.013,50.916,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"></path></g></svg>).</span> (e) OPLS-DA score plot of T2D-ctrl and db/db group (validated by permutation tests, <span class="nowrap"><svg height="11.7978pt" id="M39" style="vertical-align:-0.2063999pt" version="1.1" viewbox="-0.0498162 -11.5914 64.6874 11.7978" width="64.6874pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M610 18C585 26 567 34 540 68C517 97 499 128 476 171C452 215 425 276 413 304C496 332 570 394 570 494C570 555 545 595 509 619S419 650 364 650H139L133 622C216 615 219 612 203 527L129 132C112 40 105 36 23 28L17 0H279L285 28C199 34 194 40 211 132L239 284H284C320 284 334 275 351 236C374 182 394 140 420 93C459 23 495 -1 592 -8H600L610 18ZM480 485C480 424 449 372 403 342C374 323 338 316 293 316H245L291 562C296 589 301 601 311 608S337 618 358 618C432 618 480 575 480 485Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,8.151,-5.741)"><path d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z"></path></g><g transform="matrix(.013,0,0,-0.013,13.098,0)"><path d="M640 650H413L406 622L438 617C475 611 483 605 463 571C422 503 346 400 296 333C264 403 215 529 199 575C189 604 191 614 228 618L262 622L271 650H30L23 622C90 615 97 609 119 553L212 321C222 295 223 285 218 259L193 127C176 39 167 33 82 28L76 0H350L356 28C266 36 257 40 275 127L303 266C308 290 314 302 328 322C396 418 454 493 498 546C551 610 565 616 631 622L640 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,25.211,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,36.474,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,42.714,0)"><path d="M113 -12C146 -12 170 11 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transform="matrix(.0091,0,0,-0.0091,9.386,-5.741)"><path d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z"></path></g><g transform="matrix(.013,0,0,-0.013,17.964,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,29.227,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,35.467,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,38.431,0)"><path d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"></path></g><g transform="matrix(.013,0,0,-0.013,44.671,0)"><path d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"></path></g><g transform="matrix(.013,0,0,-0.013,50.911,0)"><path d="M412 140C382 77 369 73 315 73H129L270 222C362 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The colored boxes on the right indicated the relative concentrations of the corresponding metabolite in each group under study.</div>

BioMed Research International

fig7

Figure 7

Figure 7: Artemether Alleviates Diabetic Kidney Disease by Modulating Amino Acid Metabolism 