PMID- 37820726
OWN - NLM
STAT- MEDLINE
DCOM- 20231030
LR  - 20231110
IS  - 2667-2375 (Electronic)
IS  - 2667-2375 (Linking)
VI  - 3
IP  - 10
DP  - 2023 Oct 23
TI  - Insulin C-peptide secretion on-a-chip to measure the dynamics of secretion and 
      metabolism from individual islets.
PG  - 100602
LID - S2667-2375(23)00254-0 [pii]
LID - 10.1016/j.crmeth.2023.100602 [doi]
LID - 100602
AB  - First-phase glucose-stimulated insulin secretion is mechanistically linked to 
      type 2 diabetes, yet the underlying metabolism is difficult to discern due to 
      significant islet-to-islet variability. Here, we miniaturize a fluorescence 
      anisotropy immunoassay onto a microfluidic device to measure C-peptide secretion 
      from individual islets as a surrogate for insulin (InsC-chip). This method 
      measures secretion from up to four islets at a time with  approximately 7 s resolution while 
      providing an optical window for real-time live-cell imaging. Using the InsC-chip, 
      we reveal two glucose-dependent peaks of insulin secretion (i.e., a double peak) 
      within the classically defined 1(st) phase (<10 min). By combining real-time 
      secretion and live-cell imaging, we show islets transition from glycolytic to 
      oxidative phosphorylation (OxPhos)-driven metabolism at the nadir of the peaks. 
      Overall, these data validate the InsC-chip to measure glucose-stimulated insulin 
      secretion while revealing new dynamics in secretion defined by a shift in glucose 
      metabolism.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Wang, Yufeng
AU  - Wang Y
AD  - Advanced Diagnostics, Toronto General Hospital Research Institute, Toronto, ON 
      M5G 1L7, Canada; Institute of Biomedical Engineering, University of Toronto, 
      Toronto, ON M5S 3G9, Canada.
FAU - Regeenes, Romario
AU  - Regeenes R
AD  - Advanced Diagnostics, Toronto General Hospital Research Institute, Toronto, ON 
      M5G 1L7, Canada; Institute of Biomedical Engineering, University of Toronto, 
      Toronto, ON M5S 3G9, Canada.
FAU - Memon, Mahnoor
AU  - Memon M
AD  - Advanced Diagnostics, Toronto General Hospital Research Institute, Toronto, ON 
      M5G 1L7, Canada; Institute of Biomedical Engineering, University of Toronto, 
      Toronto, ON M5S 3G9, Canada.
FAU - Rocheleau, Jonathan V
AU  - Rocheleau JV
AD  - Advanced Diagnostics, Toronto General Hospital Research Institute, Toronto, ON 
      M5G 1L7, Canada; Institute of Biomedical Engineering, University of Toronto, 
      Toronto, ON M5S 3G9, Canada; Departments of Medicine and Physiology, University 
      of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: 
      jon.rocheleau@utoronto.ca.
LA  - eng
PT  - Journal Article
DEP - 20231010
PL  - United States
TA  - Cell Rep Methods
JT  - Cell reports methods
JID - 9918227360606676
RN  - 0 (C-Peptide)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Humans
MH  - *Islets of Langerhans/metabolism
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - C-Peptide/metabolism
MH  - Glucose/pharmacology
MH  - Lab-On-A-Chip Devices
PMC - PMC10626205
OTO - NOTNLM
OT  - CP: Biotechnology
OT  - CP: Metabolism
OT  - insulin
OT  - islet
OT  - islet-on-a-chip
OT  - live cell imaging
OT  - microfluidic
OT  - microscopy
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2023/10/12 00:42
MHDA- 2023/10/30 06:47
PMCR- 2023/10/10
CRDT- 2023/10/11 19:14
PHST- 2023/04/11 00:00 [received]
PHST- 2023/08/16 00:00 [revised]
PHST- 2023/09/15 00:00 [accepted]
PHST- 2023/10/30 06:47 [medline]
PHST- 2023/10/12 00:42 [pubmed]
PHST- 2023/10/11 19:14 [entrez]
PHST- 2023/10/10 00:00 [pmc-release]
AID - S2667-2375(23)00254-0 [pii]
AID - 100602 [pii]
AID - 10.1016/j.crmeth.2023.100602 [doi]
PST - ppublish
SO  - Cell Rep Methods. 2023 Oct 23;3(10):100602. doi: 10.1016/j.crmeth.2023.100602. 
      Epub 2023 Oct 10.