{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T23:24:22Z","timestamp":1750202662828,"version":"3.40.5"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01EB027648\u201001A1"],"award-info":[{"award-number":["1R01EB027648\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Ultrasound Medicine"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Diabetes mellitus is a complex heterogenous metabolic disease that significantly affects the world population. Although many treatments exist, including medications such as metformin, sulfonylureas, and glucagon\u2010like peptide\u20101 (GLP) receptor agonist, there is growing interest in finding alternative methods to noninvasively treat this disease. It has been previously shown that low\u2010intensity ultrasound stimulation of pancreatic \u03b2\u2010cells in mice can elicit insulin secretion as a potential treatment for this disease. This is desirable as therapeutic ultrasound has the ability to induce bioeffects while selectively focusing deep within tissues, allowing for modulation of hormone secretion in the pancreas to mitigate insufficient levels of insulin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Exactly 800\u2009kHz ultrasound with intensity 0.5\u2009W\/cm<jats:sup>2<\/jats:sup> was administered 5\u2009minutes continuously, that is, 100% duty cycle, to donor pancreatic human islets, followed by 1\u2009hour incubation and RT\u2010qPCR to assess the effect of ultrasound stimulation on gene expression. The genes were insulin (INS), glucagon (Glu), amylin (Amy), and binding immunoglobulin protein (BiP). Nine donor pancreatic human islets were used to assess insulin and glucagon secretion, while eight samples were used for amylin and BiP. Fold change (FC) was calculated to analyze the effect of ultrasound stimulation on the gene expression of the donor islet cells. High\u2010glucose and thapsigargin\u2010treated islets were utilized as positive controls. Cell viability testing was done using a Trypan Blue Exclusion Test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ultrasound stimulation did not cause a statistically significant upregulation in any of the tested genes (INS FC\u2009=\u20091.15, <jats:italic>P<\/jats:italic>\u2010value\u2009=\u2009.5692; Glu FC\u2009=\u20091.60, <jats:italic>P<\/jats:italic>\u2010value\u2009=\u2009.2231; Amy FC, <jats:italic>P<\/jats:italic>\u2010value\u2009=\u2009.2863; BiP FC\u2009=\u20092.68, <jats:italic>P<\/jats:italic>\u2010value\u2009=\u2009.3907).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results of this study show that the proposed ultrasound treatment parameters do not appear to significantly affect gene expression of any gene tested.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jum.16441","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T07:24:35Z","timestamp":1709105075000},"page":"1131-1141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Analyzing Gene Expression After Administration of Low\u2010Intensity Therapeutic Ultrasound in Human Islet Cells"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5962-3248","authenticated-orcid":false,"given":"John","family":"Hill","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering The George Washington University  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Messina","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The George Washington University  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandar","family":"Jeremic","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences The George Washington University  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7572-3922","authenticated-orcid":false,"given":"Vesna","family":"Zderic","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The George Washington University  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Centers for Disease Control and Prevention website.What is Diabetes?https:\/\/www.cdc.gov\/diabetes\/basics\/diabetes.html#:~:text=Morethan37millionUS limbamputationsCandadultblindness."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.11491116"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147644"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2010.05.011"},{"key":"e_1_2_8_6_1","unstructured":"Centers for Disease Control and Prevention.Gestational diabetes. https:\/\/www.cdc.gov\/diabetes\/basics\/gestational.html#:~:text=Gestationaldiabetesisatype areaffectedbygestationaldiabetes."},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2522\/ptj.20080020"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00063.2017"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/2040622314548679"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v4.i4.114"},{"key":"e_1_2_8_11_1","unstructured":"National Center for Biotechnology Information.TCF7L2 transcription factor 7 like 2 [homo sapiens (human)]\u2014gene\u2014NCBI."},{"key":"e_1_2_8_12_1","first-page":"59","article-title":"The islets of Langerhans. Preface","volume":"654","author":"Islam MS","year":"2010","journal-title":"Adv Exp Med Biol"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62154-6"},{"key":"e_1_2_8_14_1","unstructured":"The Pancreas Center Website.The pancreas and its function. https:\/\/columbiasurgery.org\/pancreas\/pancreas-and-its-functions#:~:text=Thepancreasisanorgan functionthatregulatesbloodsugar."},{"key":"e_1_2_8_15_1","first-page":"19","article-title":"Insulin and insulin resistance","volume":"26","author":"Wilcox G","year":"2005","journal-title":"Clin Biochem Rev"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/emm.2016.6","article-title":"Pancreatic regulation of glucose homeostasis","volume":"48","author":"R\u00f6der PV","year":"2016","journal-title":"Exp Mol Med"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2010.09.010"},{"key":"e_1_2_8_18_1","unstructured":"Centers for Disease Control and Prevention Website.Type 2 diabetes. https:\/\/cdc.gov\/diabetes\/basics\/type2.html#:~:text=Morethan37millionAmericans adultsarealsodevelopingit."},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2009.0192"},{"volume-title":"Management of Persistent Hyperglycemia in Type 2 Diabetes Mellitus","year":"2023","author":"Wexler DJ","key":"e_1_2_8_20_1"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2013.06.005"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.7863\/jum.2012.31.4.623"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13050855"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1109\/RBME.2016.2555760"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370220982301"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.4155\/tde.14.10"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1056\/NEJMoa1600159","article-title":"A randomized trial of focused ultrasound thalamotomy for essential tremor","volume":"375","author":"Elias WJ","year":"2016","journal-title":"N Engl J Med"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.joca.2016.10.003","article-title":"Low\u2010intensity pulsed ultrasound (LIPUS) treatment of cultured chondrocytes stimulates production of CCN family protein 2 (CCN2), a protein involved in the regeneration of articular cartilage: mechanism underlying this stimulation","volume":"5","author":"Nishida T","year":"2017","journal-title":"Osteoarthr Cartil"},{"key":"e_1_2_8_29_1","first-page":"1","article-title":"Therapeutic ultrasound for carpal tunnel syndrome","volume":"3","author":"Page MJ","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-chembioeng-060817-084034"},{"key":"e_1_2_8_31_1","unstructured":"PiranerDI AbediMH MoserBA Lee\u2010GosselinA ShapiroMG.Tunable thermal bioswitches for in vivo control of microbial therapeutics. In: Food Pharmaceutical and Bioengineering Division 2017 \u2013 Core Programming Area at the 2017 AIChE Annual Meeting; 2017."},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acra.2007.04.008"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultsonch.2008.10.007"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultsonch.2012.05.007"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2008.01.013"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultrasmedbio.2017.01.007"},{"key":"e_1_2_8_37_1","unstructured":"Qiagen Website.RNeasy Plus Mini Kit Quick\u2010Start Protocol.https:\/\/www.qiagen.com\/us\/products\/discovery\u2010and\u2010translational\u2010research\/dna\u2010rna\u2010purification\/rna\u2010purification\/total\u2010rna\/rneasy\u2010plus\u2010kits."},{"key":"e_1_2_8_38_1","first-page":"1","article-title":"Calcium\u2010dependent ultrasound stimulation of secretory events from pancreatic beta cells","volume":"5","author":"Castellanos IS","year":"2017","journal-title":"J Ther Ultrasound"},{"key":"e_1_2_8_39_1","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/s41598-019-49933-0","article-title":"Improving the function and engraftment of transplanted pancreatic islets using pulsed focused ultrasound therapy","volume":"9","author":"Razavi M","year":"2019","journal-title":"Sci Rep"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1144182"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806936106"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004735"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27031021"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.05.019"}],"container-title":["Journal of Ultrasound in Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jum.16441","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T06:35:06Z","timestamp":1715668506000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jum.16441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,27]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/jum.16441"],"URL":"https:\/\/doi.org\/10.1002\/jum.16441","archive":["Portico"],"relation":{},"ISSN":["0278-4297","1550-9613"],"issn-type":[{"type":"print","value":"0278-4297"},{"type":"electronic","value":"1550-9613"}],"subject":[],"published":{"date-parts":[[2024,2,27]]},"assertion":[{"value":"2023-09-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}