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Here, we thus combined high-fat\/high-fructose diet, with multiple low-dose injections of streptozotocin (HF\/HF\/Stz) to emulate the long-term complications of T2DM. HF\/HF\/Stz rats, monitored over 56 weeks, exhibited metabolic dysfunctions associated with the different stages of the T2DM disease progression in humans: an early prediabetic phase characterized by an hyperinsulinemic period with modest dysglycemia, followed by a late stage of T2DM with frank hyperglycemia, normalization of insulinemia, marked dyslipidemia, hepatic fibrosis and pancreatic \u03b2-cell failure. Histopathological analyses combined to [<jats:sup>18<\/jats:sup>F]-FDG PET imaging further demonstrated the presence of several end-organ long-term complications, including reduction in myocardial glucose utilization, renal dysfunction as well as microvascular neuropathy and retinopathy. We also provide for the first time a comprehensive \u00b5-PET whole brain imaging of the changes in glucose metabolic activity within discrete cerebral regions in HF\/HF\/Stz diabetic rats. Altogether, we developed and characterized a unique non-genetic preclinical model of T2DM adapted to the current diet and lifestyle that recapitulates the major metabolic features of the disease progression, from insulin resistance to pancreatic \u03b2-cell dysfunction, and closely mimicking the target-organ damage occurring in type 2 diabetic patients at advanced stages.<\/jats:p>","DOI":"10.1038\/s41598-017-18896-5","type":"journal-article","created":{"date-parts":[[2018,1,5]],"date-time":"2018-01-05T10:25:46Z","timestamp":1515147946000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":153,"title":["Combination of high-fat\/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications"],"prefix":"10.1038","volume":"8","author":[{"given":"David Andr\u00e9","family":"Barri\u00e8re","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Noll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Roussy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Lizotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anissa","family":"Kessai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karyn","family":"Kirby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Belleville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Beaudet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"Longpr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 C.","family":"Carpentier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2613-6710","authenticated-orcid":false,"given":"Pedro","family":"Geraldes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Sarret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,11]]},"reference":[{"key":"18896_CR1","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1002\/iub.1396","volume":"67","author":"A Pandey","year":"2015","unstructured":"Pandey, A., Chawla, S. & Guchhait, P. 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