PMID- 26041305
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20191210
IS  - 1520-6882 (Electronic)
IS  - 0003-2700 (Linking)
VI  - 87
IP  - 13
DP  - 2015 Jul 7
TI  - High Temporal Resolution Detection of Patient-Specific Glucose Uptake from Human 
      ex Vivo Adipose Tissue On-Chip.
PG  - 6535-43
LID - 10.1021/ac504730r [doi]
AB  - Human tissue in vitro models on-chip are highly desirable to dissect the 
      complexity of a physio-pathological in vivo response because of their advantages 
      compared to traditional static culture systems in terms of high control of 
      microenvironmental conditions, including accurate perturbations and high temporal 
      resolution analyses of medium outflow. Human adipose tissue (hAT) is a key player 
      in metabolic disorders, such as Type 2 Diabetes Mellitus (T2DM). It is involved 
      in the overall energy homeostasis not only as passive energy storage but also as 
      an important metabolic regulator. Here, we aim at developing a large scale 
      microfluidic platform for generating high temporal resolution of glucose uptake 
      profiles, and consequently insulin sensitivity, under physio-pathological 
      stimulations in ex vivo adipose tissues from nondiabetic and T2DM individuals. A 
      multiscale mathematical model that integrates fluid dynamics and an intracellular 
      insulin signaling pathway description was used for assisting microfluidic design 
      in order to maximize measurement accuracy of tissue metabolic activity in 
      response to perturbations. An automated microfluidic injection system was 
      included on-chip for performing precise dynamic biochemical stimulations. The 
      temporal evolution of culture conditions could be monitored for days, before and 
      after perturbation, measuring glucose concentration in the outflow with high 
      temporal resolution. As a proof of concept for detection of insulin resistance, 
      we measured insulin-dependent glucose uptake by hAT from nondiabetic and T2DM 
      subjects, mimicking the postprandial response. The system presented thus 
      represents an important tool in dissecting the role of single tissues, such as 
      hAT, in the complex interwoven picture of metabolic diseases.
FAU - Zambon, Alessandro
AU  - Zambon A
AD  - daggerDepartment of Industrial Engineering, University of Padova, Padova 35131, Italy.
AD  - double daggerVenetian Institute of Molecular Medicine, Padova, 35129 Italy.
FAU - Zoso, Alice
AU  - Zoso A
AD  - daggerDepartment of Industrial Engineering, University of Padova, Padova 35131, Italy.
AD  - double daggerVenetian Institute of Molecular Medicine, Padova, 35129 Italy.
FAU - Gagliano, Onelia
AU  - Gagliano O
AD  - daggerDepartment of Industrial Engineering, University of Padova, Padova 35131, Italy.
AD  - double daggerVenetian Institute of Molecular Medicine, Padova, 35129 Italy.
FAU - Magrofuoco, Enrico
AU  - Magrofuoco E
AD  - daggerDepartment of Industrial Engineering, University of Padova, Padova 35131, Italy.
AD  - double daggerVenetian Institute of Molecular Medicine, Padova, 35129 Italy.
FAU - Fadini, Gian Paolo
AU  - Fadini GP
AD  -  section signDepartment of Medicine, University of Padova, Padova 35128, Italy.
FAU - Avogaro, Angelo
AU  - Avogaro A
AD  -  section signDepartment of Medicine, University of Padova, Padova 35128, Italy.
FAU - Foletto, Mirto
AU  - Foletto M
AD  -  parallelDepartment of Surgery, Oncology and Gastroenterology, University of Padova, 
      Padova 35124, Italy.
FAU - Quake, Stephen
AU  - Quake S
AD  -  perpendicularBioengineering and Applied Physics, Stanford University, Stanford, California 
      94305, United States.
AD  - #Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, United States.
FAU - Elvassore, Nicola
AU  - Elvassore N
AD  - daggerDepartment of Industrial Engineering, University of Padova, Padova 35131, Italy.
AD  - double daggerVenetian Institute of Molecular Medicine, Padova, 35129 Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20150625
PL  - United States
TA  - Anal Chem
JT  - Analytical chemistry
JID - 0370536
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adipose Tissue/*metabolism
MH  - Diabetes Mellitus, Type 2/metabolism
MH  - Glucose/*metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Lab-On-A-Chip Devices
EDAT- 2015/06/05 06:00
MHDA- 2015/12/17 06:00
CRDT- 2015/06/05 06:00
PHST- 2015/06/05 06:00 [entrez]
PHST- 2015/06/05 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
AID - 10.1021/ac504730r [doi]
PST - ppublish
SO  - Anal Chem. 2015 Jul 7;87(13):6535-43. doi: 10.1021/ac504730r. Epub 2015 Jun 25.