Combination of high-fat/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications

The epidemic of type 2 diabetes mellitus (T2DM) is fueled by added fructose consumption. 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, exhibi...

Full description

Saved in:

Bibliographic Details
Published in:	Scientific reports Vol. 8; no. 1; p. 424
Main Authors:	Barrière, David André, Noll, Christophe, Roussy, Geneviève, Lizotte, Farah, Kessai, Anissa, Kirby, Karyn, Belleville, Karine, Beaudet, Nicolas, Longpré, Jean-Michel, Carpentier, André C., Geraldes, Pedro, Sarret, Philippe
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 11-01-2018 Nature Publishing Group
Subjects:	101/28 13/1 13/51 14/63 59/57 59/78 631/443/319/1642/137/773 692/163/2743/137/138 Animals Diabetes Diabetes Complications - diagnostic imaging Diabetes Complications - metabolism Diabetes Complications - pathology Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Experimental - complications Diabetic neuropathy Diet Diet, High-Fat - adverse effects Disease Progression Disease resistance Dyslipidemia Fibrosis Fluorodeoxyglucose F18 - metabolism Fructose Fructose - adverse effects Glucose metabolism High fat diet Humanities and Social Sciences Humans Hyperglycemia Insulin Insulin Resistance Male Metabolism Microvasculature Mimicry multidisciplinary Neuroimaging Nutrient deficiency Pancreas Positron emission tomography Prediabetic State - diagnosis Rats Renal function Retinopathy Rodents Science Science (multidisciplinary) Streptozocin
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The epidemic of type 2 diabetes mellitus (T2DM) is fueled by added fructose consumption. 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 β-cell failure. Histopathological analyses combined to [ 18 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 µ-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 β-cell dysfunction, and closely mimicking the target-organ damage occurring in type 2 diabetic patients at advanced stages.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-017-18896-5