{"id":2132,"date":"2011-09-26T00:00:00","date_gmt":"2011-09-26T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\/"},"modified":"2011-09-26T00:00:00","modified_gmt":"2011-09-26T07:00:00","slug":"discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\/","title":{"rendered":"Discovery of insulin switches in pancreas could lead to new diabetes drugs"},"content":{"rendered":"

LA JOLLA, CA\u2014Researchers at the Salk Institute have discovered how a hormone turns on a series of molecular switches inside the pancreas that increases production of insulin.\n<\/p>\n

\nThe finding, published today in the Proceedings of the National Academy of Sciences<\/em>, raises the possibility that new designer drugs might be able to turn on key molecules in this pathway to help the 80 million Americans who have type 2 diabetes or pre-diabetic insulin resistance.\n<\/p>\n

\nThe molecular switches command pancreatic beta islet cells, the cells responsible for insulin, to grow and multiply. Tweaking these cells might offer a solution to type 1 diabetes, the form of diabetes caused by destruction of islet cells, and to type II diabetes, the form caused by insulin resistance.\n<\/p>\n

\n“By understanding how pancreatic cells can be encouraged to produce insulin in the most efficient way possible, we may be able to manipulate those cells to treat or even prevent diabetes,” says the study’s lead author, Marc Montminy<\/a>, a professor in the \u514b\u83b1\u987f\u57fa\u91d1\u4f1a\u80bd\u751f\u7269\u5b66\u5b9e\u9a8c\u5ba4<\/a> at Salk.\n<\/p>\n

\nSuch new agents might increase the functioning of beta islet cells even in people who have not developed diabetes.\n<\/p>\n

\n“The truth is that as we grow older, these islet cells tend to wear out,” Montminy says. “The genetic switches just don’t get turned on as efficiently as they did when we were younger, even if we don’t develop diabetes. It’s like using a garage door opener so many times, the battery wears out. We need a way to continually refresh that battery.”\n<\/p>\n

\nType II diabetes is caused by an inability for insulin to stimulate muscles to take up glucose, a kind of sugar, from the bloodstream after eating. Age is a risk factor for diabetes, as is obesity, genetic predisposition and lack of physical exercise.\n<\/p>\n

\nMontminy and two researchers in his lab, Sam Van de Velde, a post-doctoral research associate, and Megan F. Hogan, a graduate student, set out to study how glucagon-like peptide-1 (GLP-1), a hormone produced in the gastrointestinal tract, promotes islet cell survival and growth.\n<\/p>\n

\nThe question is important, not only to understanding basic insulin biology, but also because it would help explain how a drug approved to treat diabetes in 2005 actually works.\n<\/p>\n

\nThat drug, exenatide (Byetta), is a synthetic version of extendin-4, a hormone found in the saliva of the Gila monster lizard. Extendin-4 is similar to GLP-1 in humans, but is much longer acting. “The Gila monster hibernates most of its life, feeding only twice a year, so it needs a way of storing food really well, which means its insulin has to be very efficient,” says Montminy.\n<\/p>\n

\nGLP-1 has a very short duration because enzymes in the bloodstream break it down quickly after it activates insulin production, he says. Patients using exenatide, on the other hand, need to inject it only twice a day.\n<\/p>\n

\nAs helpful as that drug is, Montminy reasoned that if he could pinpoint the various switches that GLP-1 turns on to promote insulin secretion, it might be possible to identify drug targets that might be even more efficient for human use than exenatide.\n<\/p>\n

\nThe researchers set out to identify the various players in the molecular pathway that is activated when GLP-1 docks onto its receptor on the surface of islet cells. In his previous work, Montminy had already discovered that one of the first switches activated is CREB, which turns on other genes.\n<\/p>\n

\nIn this study they defined other players “downstream” of CREB – discoveries that turned out to be surprising. Two of the molecules, mTOR and HIF, are heavily implicated in cancer development, Montminy says. For example, mTOR is a critical sensor of energy in cells, and HIF works inside cells to reprogram genes to help cells grow and divide.\n<\/p>\n

\n“Turning on switches inside a cell is a bit like running a relay race,” Montminy says. “GLP-1 activates CREB, which passes the baton to mTOR, and then HIF takes over to help islet cells withstand the stresses that cause wear and tear, such as aging. It stands to reason that mTOR and HIF would be involved in helping islet cells to remain healthy because they are involved in cell growth – in this case, growth of islet cells.”\n<\/p>\n

\nThese findings suggest it may be possible to activate these molecular players independently to restore insulin production, Montminy says. A drug could directly activate the HIF switch, for example, bypassing the prior steps in the pathway: GLP-1, CREB and mTOR. That might not only increase production of insulin from existing islet cells, but also promote growth of new islet cells.\n<\/p>\n

\nThe findings have other clinical implications as well. Understanding that mTOR is involved in insulin secretion helps explain why some transplant patients develop diabetes. Rapamycin, a drug often used to prevent organ rejection, suppresses mTOR activity, and so probably undermines insulin production.\n<\/p>\n

\nKnowing that activating HIF also may help islet cells grow could be useful in efforts to transplant islet cells in patients with type 1 diabetes.\n<\/p>\n

\nThe study was funded by the Juvenile Diabetes Research Foundation, the National Institutes of Health, the Keickhefer Foundation, the Clayton Foundation for Medical Research, the Leona M. and Harry B. Helmsley Charitable Trust and by Charles Brandes.<\/p>\n

About the Salk Institute for Biological Studies:<\/strong>
\nThe Salk Institute for Biological Studies is one of the world’s preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer’s, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.\n<\/p>\n

\nFaculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[100],"disease-research":[],"class_list":["post-2132","disclosure","type-disclosure","status-publish","hentry","faculty-marc-montminy"],"acf":[],"yoast_head":"\nDiscovery of insulin switches in pancreas could lead to new diabetes drugs - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Discovery of insulin switches in pancreas could lead to new diabetes drugs - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA, CA\u2014Researchers at the Salk Institute have discovered how a hormone turns on a series of molecular switches inside the pancreas that increases production of insulin.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.salk.edu\/zh\/news-release\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\/\" \/>\n<meta property=\"og:site_name\" content=\"Salk Institute for Biological Studies\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk-institute-preview-image.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"628\" \/>\n\t<meta property=\"og:image:height\" content=\"329\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\\\/\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\\\/\",\"name\":\"Discovery of insulin switches in pancreas could lead to new diabetes drugs - Salk Institute for Biological Studies\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\"},\"datePublished\":\"2011-09-26T07:00:00+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\\\/#breadcrumb\"},\"inLanguage\":\"zh-CN\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.salk.edu\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Discovery of insulin switches in pancreas could lead to new diabetes drugs\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"name\":\"Salk Institute for Biological Studies\",\"description\":\"The Power of Science\",\"publisher\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.salk.edu\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"zh-CN\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\",\"name\":\"Salk Institute for Biological Studies\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"zh-CN\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"contentUrl\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"width\":696,\"height\":696,\"caption\":\"Salk Institute for Biological Studies\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Discovery of insulin switches in pancreas could lead to new diabetes drugs - Salk Institute for Biological Studies","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.salk.edu\/zh\/news-release\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\/","og_locale":"zh_CN","og_type":"article","og_title":"Discovery of insulin switches in pancreas could lead to new diabetes drugs - Salk Institute for Biological Studies","og_description":"LA JOLLA, CA\u2014Researchers at the Salk Institute have discovered how a hormone turns on a series of molecular switches inside the pancreas that increases production of insulin.","og_url":"https:\/\/www.salk.edu\/zh\/news-release\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\/","og_site_name":"Salk Institute for Biological Studies","og_image":[{"width":628,"height":329,"url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk-institute-preview-image.jpg","type":"image\/jpeg"}],"twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"5 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.salk.edu\/news-release\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\/","url":"https:\/\/www.salk.edu\/news-release\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\/","name":"Discovery of insulin switches in pancreas could lead to new diabetes drugs - Salk Institute for Biological Studies","isPartOf":{"@id":"https:\/\/www.salk.edu\/#website"},"datePublished":"2011-09-26T07:00:00+00:00","breadcrumb":{"@id":"https:\/\/www.salk.edu\/news-release\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\/#breadcrumb"},"inLanguage":"zh-CN","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.salk.edu\/news-release\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/www.salk.edu\/news-release\/discovery-of-insulin-switches-in-pancreas-could-lead-to-new-diabetes-drugs\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.salk.edu\/"},{"@type":"ListItem","position":2,"name":"Discovery of insulin switches in pancreas could lead to new diabetes drugs"}]},{"@type":"WebSite","@id":"https:\/\/www.salk.edu\/#website","url":"https:\/\/www.salk.edu\/","name":"\u7d22\u5c14\u514b\u751f\u7269\u7814\u7a76\u6240","description":"The Power of Science","publisher":{"@id":"https:\/\/www.salk.edu\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.salk.edu\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"zh-CN"},{"@type":"Organization","@id":"https:\/\/www.salk.edu\/#organization","name":"\u7d22\u5c14\u514b\u751f\u7269\u7814\u7a76\u6240","url":"https:\/\/www.salk.edu\/","logo":{"@type":"ImageObject","inLanguage":"zh-CN","@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/","url":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","contentUrl":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","width":696,"height":696,"caption":"Salk Institute for Biological Studies"},"image":{"@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/"}}]}},"ACF":{"paper_url":"","journal_title":"","paper_author_list":"","paper_title":"","subhead":"Salk researches identify cellular mechanism in the pancreas could lead to new diabetes drugs","home_photo":"2011\/MontminyVandeVeldeHeadshot.jpg","listing_photo":"","line_2":"Salk researches identify cellular mechanism in the pancreas could lead to new diabetes drugs","line_1":"Discovery of insulin switches in pancreas could lead to new diabetes drugs"},"_links":{"self":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure\/2132","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure"}],"about":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/types\/disclosure"}],"version-history":[{"count":0,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure\/2132\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/media?parent=2132"}],"wp:term":[{"taxonomy":"faculty","embeddable":true,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/faculty?post=2132"},{"taxonomy":"disease-research","embeddable":true,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disease-research?post=2132"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}