{"id":872,"date":"2023-12-12T12:40:18","date_gmt":"2023-12-12T12:40:18","guid":{"rendered":"https:\/\/dev.minervainstitute.fi\/amnesomsattning\/"},"modified":"2024-11-04T09:38:52","modified_gmt":"2024-11-04T09:38:52","slug":"amnesomsattning","status":"publish","type":"page","link":"https:\/\/minervainstitute.fi\/sv\/forskningsgrupper\/amnesomsattning\/","title":{"rendered":"\u00c4mnesoms\u00e4ttning"},"content":{"rendered":"

\u00c4mnesoms\u00e4ttning<\/h1>\n<\/div>
<\/div><\/div>

Gruppens huvudsakliga intresse \u00e4r att f\u00f6rst\u00e5 de olika mekanismer som reglerar \u00e4mnesoms\u00e4ttningen och insulink\u00e4nsligheten i hela kroppen s\u00e5v\u00e4l som specifikt i skelettmuskulaturen. Vi \u00e4r intresserade av molekyl\u00e4ra och genetiska mekanismer som bidrar till typ 2-diabetes (T2D) och relaterade egenskaper. <\/p>\n

Vi \u00e4r intresserade av hur \u00e4mnesoms\u00e4ttningen regleras och s\u00e4rskilt av de molekyl\u00e4ra mekanismer som reglerar insulinverkan i m\u00e4nniskans skelettmuskulatur. Som en huvudforskningsmodell anv\u00e4nder vi prim\u00e4ra muskelcellskulturer, etablerade fr\u00e5n muskelbiopsier erh\u00e5llna fr\u00e5n kliniskt noggrant karakteriserade frivilliga f\u00f6rs\u00f6kspersoner. Vi analyserar mekanismerna som predisponerar och leder till insulinresistens, och s\u00f6ker efter nya s\u00e4tt att f\u00f6rb\u00e4ttra insulinets verkan. Vi har en m\u00e4ngd olika in vitro-metoder f\u00f6r att studera cellmetabolismen till v\u00e5rt f\u00f6rfogande. <\/p>\n

Finland-United States Investigation of NIDDM Genetics (FUSION) \u00e4r ett internationellt multi-organisatoriskt samarbetsprojekt, vars huvudsakliga m\u00e5l \u00e4r att identifiera genetiska riskfaktorer som predisponerar f\u00f6r typ 2-diabetes och relaterade intermedi\u00e4ra egenskaper. Vi har ett n\u00e4ra samarbete med FUSION-studien, d\u00e4r gruppchefen, Docent Heikki Koistinen, \u00e4r en av FUSION:s ansvariga pr\u00f6vare. Som ett exempel p\u00e5 hur forskningsfr\u00e5gor och samarbeten str\u00e5lar samman p\u00e5 ett fruktbart s\u00e4tt, har vi identifierat en missense-variant p.P50T\/AKT2 som en del av de p\u00e5g\u00e5ende genetiska analyserna av FUSION – och METSIM-studier (Metabolic Syndrome in Men – studien). Denna variant \u00e4r specifik f\u00f6r finl\u00e4ndare och mycket s\u00e4llsynt hos icke-finska europ\u00e9er. Den predisponerar f\u00f6r insulinresistens och typ 2-diabetes. Vi har etablerat en internationellt unik och mycket stor samling av prim\u00e4ra muskelcellskulturer fr\u00e5n b\u00e4rare av den finska p.P50T\/AKT2-varianten och har p\u00e5visat en storskalig f\u00f6rs\u00e4mring av insulinsignaleringen i myotuber fr\u00e5n variantb\u00e4rare (M\u00e4kinen et al. 2023).<\/p>\n<\/div><\/div><\/div>

<\/span><\/div>

Gruppledare<\/h3>\n

Heikki Koistinen, MD, DrMedSci, professor
\nheikki.koistinen@helsinki.fi<\/p>\n<\/div>

Gruppmedlemmar<\/h3>\n

Sreesha Sree, PhD
\nSelina M\u00e4kinen, PhD
\nHenric Kultalahti, MK
\nLeena Kinnunen, FK, forskningsassistent<\/p>\n<\/div><\/div><\/div>

<\/span><\/div>

Gruppledare<\/h3>\n

Heikki Koistinen, MD, DrMedSci, professor
\nheikki.koistinen@helsinki.fi<\/p>\n<\/div>

Gruppmedlemmar<\/h3>\n

Sreesha Sree, PhD
\nSelina M\u00e4kinen, PhD
\nHenric Kultalahti, MK
\nLeena Kinnunen, FK, forskningsassistent<\/p>\n<\/div><\/div><\/div><\/div><\/div>

Utvalda publikationer<\/h3>\n<\/div>
<\/div><\/div>

M\u00e4kinen S, Datta N, Rangarajan S, Nguyen YH, Olkkonen VM, Latva-Rasku A, Nuutila P, Laakso M, Koistinen HA: Finnish-specific AKT2<\/em> gene variant leads to impaired insulin signalling in myotubes. Journal of Molecular Endocrinology. 2023 Jan 4;70(2):e210285. doi: 10.1530\/JME-21-0285. Print 2023 Feb 1. PMID: 36409629<\/p>\n

\u00d6hman T, Teppo J, Datta N, M\u00e4kinen S, Varjosalo M, Koistinen HA: Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes. iScience 2021 Jun 10;24(7):102712. doi: 10.1016\/j.isci.2021.102712. eCollection 2021 Jul 23. PMID: 34235411<\/p>\n

M\u00e4kinen S, Datta N, Nguyen YH, Kyrylenko P, Laakso M, Koistinen HA: Simvastatin profoundly impairs energy metabolism in primary human muscle cells. Endocrine Connections, 9(11):1103-1113, 2020, doi: 10.1530\/EC-20-0444. PMID: 33295884<\/p>\n

Taylor DL , Scott LJ , Jackson AU, Narisu N , Hemani G , Erdos MR , Chines PS , Swift A , Idol J , Didion JP , Welch RP , Kinnunen L , Saramies J , Lakka TA , Laakso M , Tuomilehto J , Parker SCJ, Koistinen HA , Smith GD , Boehnke M , Birney E , Collins FS : Integrative analysis of gene expression, DNA methylation, physiological traits, and genetic variation in human skeletal muscle. Proc Natl Acad Sci U S A. 16(22):10883-10888. 2019 May 10. pii: 201814263. doi: 10.1073\/pnas.1814263116. [Epub ahead of print] PMID: 31076557<\/p>\n

Latva-Rasku A, Honka MJ, Stan\u010d\u00e1kov\u00e1 A, Koistinen HA, Kuusisto J, Guan L, Manning AK, Stringham H, Gloyn AL, Lindgren CM, T2D-GENES-konsortiet, Collins FS, Mohlke KL, Scott LJ, Karjalainen T, Nummenmaa L, Boehnke M, Nuutila P, Laakso M: A<\/em> Partial Loss-of-Function Variant in AKT2<\/em> is Associated with Reduced Insulin-Mediated Glucose Uptake in Multiple Insulin Sensitive Tissues: a Genotype-Based Callback Positron Emission Tomography Study. Diabetes 2018 Feb;67(2):334-342. doi: 10.2337\/db17-1142. Epub 2017 Nov 15.PMID:29141982<\/p>\n

Scott LJ*, Erdos MR*, Huyghe JR*, Welch RP*, Beck AT, Wolford BN, Chines PS, Didion JP, Narisu N, Stringham HM, Taylor DL, Jackson AU, Vadlamudi S, Bonnycastle LL, Kinnunen L, Saramies J, Sundvall J, D’Oliveira Albanus R, Kiseleva A, Hensley J, Crawford GE, Jiang H, Wen X, Watanabe RM, Lakka TA, Mohlke KL, Laakso M, Tuomilehto J, Koistinen HA, Boehnke M*, Collins FS*, Parker SCJ*: The genetic regulatory signature of type 2 diabetes in human skeletal muscle. Nature Communications. Jun 29;7:11764, 2016. doi: 10.1038\/ncomms11764. PMID: 27353450<\/p>\n

Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, Ma C, Fontanillas P, Moutsianas L, McCarthy DJ, Rivas MA, Perry JR, Sim X, Blackwell TW, Robertson NR, Rayner NW, Cingolani P, Locke AE, Tajes JF, Highland HM, Dupuis J, Chines PS, Lindgren CM, Hartl C, Jackson AU, Chen H, Huyghe JR, van de Bunt M, Pearson RD, Kumar A, M\u00fcller-Nurasyid M, Grarup N, Stringham HM, Gamazon ER, Lee J, Chen Y, Scott RA, Below JE, Chen P, Huang J, Go MJ, Stitzel ML, Pasko D, Parker SC, Varga TV, Green T, Beer NL, Day-Williams AG, Ferreira T, Fingerlin T, Horikoshi M, Hu C, Huh I, Ikram MK, Kim BJ, Kim Y, Kim YJ, Kwon MS, Lee J, Lee S, Lin KH, Maxwell TJ, Nagai Y, Wang X, Welch RP, Yoon J, Zhang W, Barzilai N, Voight BF, Han BG, Jenkinson CP, Kuulasmaa T, Kuusisto J, Manning A, Ng MC, Palmer ND, Balkau B, Stan\u010d\u00e1kov\u00e1 A, Abboud HE, Boeing H, Giedraitis V, Prabhakaran D, Gottesman O, Scott J, Carey J, Kwan P, Grant G, Smith JD, Neale BM, Purcell S, Butterworth AS, Howson JM, Lee HM, Lu Y, Kwak SH, Zhao W, Danesh J, Lam VK, Park KS, Saleheen D, So WY, Tam CH, Afzal U, Aguilar D, Arya R, Aung T, Chan E, Navarro C, Cheng CY, Palli D, Correa A, Curran JE, Rybin D, Farook VS, Fowler SP, Freedman BI, Griswold M, Hale DE, Hicks PJ, Khor CC, Kumar S, Lehne B, Thuillier D, Lim WY, Liu J, van der Schouw YT, Loh M, Musani SK, Puppala S, Scott WR, Yengo L, Tan ST, Taylor HA Jr, Thameem F, Wilson G, Wong TY, Nj\u00f8lstad PR, Levy JC, Mangino M, Bonnycastle LL, Schwarzmayr T, Fadista J, Surdulescu GL, Herder C, Groves CJ, Wieland T, Bork-Jensen J, Brandslund I, Christensen C, Koistinen HA, Doney AS, Kinnunen L, Esko T, Farmer AJ, Hakaste L, Hodgkiss D, Kravic J, Lyssenko V, Hollensted M, J\u00f8rgensen ME, J\u00f8rgensen T, Ladenvall C, Justesen JM, K\u00e4r\u00e4j\u00e4m\u00e4ki A, Kriebel J, Rathmann W, Lannfelt L, Lauritzen T, Narisu N, Linneberg A, Melander O, Milani L, Neville M, Orho-Melander M, Qi L, Qi Q, Roden M, Rolandsson O, Swift A, Rosengren AH, Stirrups K, Wood AR, Mihailov E, Blancher C, Carneiro MO, Maguire J, Poplin R, Shakir K, Fennell T, DePristo M, Hrab\u00e9 de Angelis M, Deloukas P, Gjesing AP, Jun G, Nilsson P, Murphy J, Onofrio R, Thorand B, Hansen T, Meisinger C, Hu FB, Isomaa B, Karpe F, Liang L, Peters A, Huth C, O’Rahilly SP, Palmer CN, Pedersen O, Rauramaa R, Tuomilehto J, Salomaa V, Watanabe RM, Syv\u00e4nen AC, Bergman RN, Bharadwaj D, Bottinger EP, Cho YS, Chandak GR, Chan JC, Chia KS, Daly MJ, Ebrahim SB, Langenberg C, Elliott P, Jablonski KA, Lehman DM, Jia W, Ma RC, Pollin TI, Sandhu M, Tandon N, Froguel P, Barroso I, Teo YY, Zeggini E, Loos RJ, Small KS, Ried JS, DeFronzo RA, Grallert H, Glaser B, Metspalu A, Wareham NJ, Walker M, Banks E, Gieger C, Ingelsson E, Im HK, Illig T, Franks PW, Buck G, Trakalo J, Buck D, Prokopenko I, M\u00e4gi R, Lind L, Farjoun Y, Owen KR, Gloyn AL, Strauch K, Tuomi T, Kooner JS, Lee JY, Park T, Donnelly P, Morris AD, Hattersley AT, Bowden DW, Collins FS, Atzmon G, Chambers JC, Spector TD, Laakso M, Strom TM, Bell GI, Blangero J, Duggirala R, Tai ES, McVean G, Hanis CL, Wilson JG, Seielstad M, Frayling TM, Meigs JB, Cox NJ, Sladek R, Lander ES, Gabriel S, Burtt NP, Mohlke KL, Meitinger T, Groop L, Abecasis G, Florez JC, Scott LJ, Morris AP, Kang HM, Boehnke M, Altshuler D, McCarthy MI: The genetic architecture of type 2 diabetes. Nature, Jul 11, 536(7614):41-47, 2016. doi: 10.1038\/nature18642. PMID: 27398621<\/p>\n

Skrobuk P, von Kraemer S, Semenova MM, Zitting A, Koistinen HA: Acute exposure to resveratrol inhibits AMPK activity in human skeletal muscle cells. Diabetologia 55:3051-60, 2012. DOI 10.1007\/s00125-012-2691-1.<\/p>\n

Bouzakri K, Zachrisson A, Al-Khalili L, Zhang BB, Koistinen HA, Krook A, Zierath JR : si<\/em>RNA based gene silencing reveals specialized roles of IRS1\/Akt2 and IRS-2\/Akt1 in glucose and lipid metabolism in human skeletal muscle. Cell Metabolism 4 :89-96, 2006<\/p>\n

Koistinen HA, Galuska D, Chibalin AV, Yang J, Zierath JR, Holman GD, Wallberg-Henriksson H: AICAR (5 amino-imidazole carboxamide riboside) increases glucose transport and cell-surface GLUT4 content in skeletal muscle from Type 2 diabetic subjects. Diabetes 52:1066-1072, 2003<\/p>\n<\/div><\/div><\/div><\/div><\/div>

Finansi\u00e4rer av forskningen<\/h3>\n<\/div>
<\/div><\/div>

Finska Vetenskaps-Societeten
\nHUS-VATR
\nJalmari and Rauha Ahokaan S\u00e4\u00e4ti\u00f6
\nFinska L\u00e4kares\u00e4llskapet
\nMedicinska underst\u00f6dsf\u00f6reningen Liv och H\u00e4lsa r.f<\/p>\n<\/div><\/div><\/div><\/div><\/div>

F\u00f6lja<\/h3>\n<\/div>
<\/div><\/div>

https:\/\/researchportal.helsinki.fi\/en\/persons\/heikki-allan-koistinen<\/a><\/p>\n<\/div><\/div><\/div><\/div><\/div><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":0,"parent":878,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"100-width.php","meta":{"footnotes":""},"class_list":["post-872","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/pages\/872","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/comments?post=872"}],"version-history":[{"count":4,"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/pages\/872\/revisions"}],"predecessor-version":[{"id":1495,"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/pages\/872\/revisions\/1495"}],"up":[{"embeddable":true,"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/pages\/878"}],"wp:attachment":[{"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/media?parent=872"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}