PMID- 29323186
OWN - NLM
STAT- MEDLINE
DCOM- 20181120
LR  - 20220410
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Jan 11
TI  - Combination of high-fat/high-fructose diet and low-dose streptozotocin to model 
      long-term type-2 diabetes complications.
PG  - 424
LID - 10.1038/s41598-017-18896-5 [doi]
LID - 424
AB  - 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 beta-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 micro-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 beta-cell dysfunction, and 
      closely mimicking the target-organ damage occurring in type 2 diabetic patients 
      at advanced stages.
FAU - Barriere, David Andre
AU  - Barriere DA
AD  - Departement de Pharmacologie et Physiologie/Institut de Pharmacologie de 
      Sherbrooke, Universite de Sherbrooke, Quebec, Canada. david.a.barriere@gmail.com.
FAU - Noll, Christophe
AU  - Noll C
AD  - Departement de Medecine, Service d'Endocrinologie, Faculte de Medecine et des 
      Sciences de la Sante, Universite de Sherbrooke, Quebec, Canada.
FAU - Roussy, Genevieve
AU  - Roussy G
AD  - Departement de Pharmacologie et Physiologie/Institut de Pharmacologie de 
      Sherbrooke, Universite de Sherbrooke, Quebec, Canada.
FAU - Lizotte, Farah
AU  - Lizotte F
AD  - Departement de Medecine, Service d'Endocrinologie, Faculte de Medecine et des 
      Sciences de la Sante, Universite de Sherbrooke, Quebec, Canada.
FAU - Kessai, Anissa
AU  - Kessai A
AD  - Departement de Pharmacologie et Physiologie/Institut de Pharmacologie de 
      Sherbrooke, Universite de Sherbrooke, Quebec, Canada.
FAU - Kirby, Karyn
AU  - Kirby K
AD  - Departement de Pharmacologie et Physiologie/Institut de Pharmacologie de 
      Sherbrooke, Universite de Sherbrooke, Quebec, Canada.
FAU - Belleville, Karine
AU  - Belleville K
AD  - Departement de Pharmacologie et Physiologie/Institut de Pharmacologie de 
      Sherbrooke, Universite de Sherbrooke, Quebec, Canada.
FAU - Beaudet, Nicolas
AU  - Beaudet N
AD  - Departement de Pharmacologie et Physiologie/Institut de Pharmacologie de 
      Sherbrooke, Universite de Sherbrooke, Quebec, Canada.
FAU - Longpre, Jean-Michel
AU  - Longpre JM
AD  - Departement de Pharmacologie et Physiologie/Institut de Pharmacologie de 
      Sherbrooke, Universite de Sherbrooke, Quebec, Canada.
FAU - Carpentier, Andre C
AU  - Carpentier AC
AD  - Departement de Medecine, Service d'Endocrinologie, Faculte de Medecine et des 
      Sciences de la Sante, Universite de Sherbrooke, Quebec, Canada.
FAU - Geraldes, Pedro
AU  - Geraldes P
AUID- ORCID: 0000-0002-2613-6710
AD  - Departement de Medecine, Service d'Endocrinologie, Faculte de Medecine et des 
      Sciences de la Sante, Universite de Sherbrooke, Quebec, Canada.
FAU - Sarret, Philippe
AU  - Sarret P
AD  - Departement de Pharmacologie et Physiologie/Institut de Pharmacologie de 
      Sherbrooke, Universite de Sherbrooke, Quebec, Canada. 
      philippe.sarret@usherbrooke.ca.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180111
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 30237-26-4 (Fructose)
RN  - 5W494URQ81 (Streptozocin)
SB  - IM
MH  - Animals
MH  - Diabetes Complications/*diagnostic imaging/metabolism/pathology
MH  - Diabetes Mellitus, Experimental/*complications
MH  - Diet, High-Fat/*adverse effects
MH  - Disease Progression
MH  - Fluorodeoxyglucose F18/metabolism
MH  - Fructose/*adverse effects
MH  - Humans
MH  - Insulin Resistance
MH  - Male
MH  - Positron-Emission Tomography
MH  - Prediabetic State/diagnosis
MH  - Rats
MH  - Streptozocin
PMC - PMC5765114
COIS- The authors declare that they have no competing interests.
EDAT- 2018/01/13 06:00
MHDA- 2018/11/21 06:00
PMCR- 2018/01/11
CRDT- 2018/01/12 06:00
PHST- 2017/06/29 00:00 [received]
PHST- 2017/12/19 00:00 [accepted]
PHST- 2018/01/12 06:00 [entrez]
PHST- 2018/01/13 06:00 [pubmed]
PHST- 2018/11/21 06:00 [medline]
PHST- 2018/01/11 00:00 [pmc-release]
AID - 10.1038/s41598-017-18896-5 [pii]
AID - 18896 [pii]
AID - 10.1038/s41598-017-18896-5 [doi]
PST - epublish
SO  - Sci Rep. 2018 Jan 11;8(1):424. doi: 10.1038/s41598-017-18896-5.