Imaging Insulin Secretion from Mouse Pancreas by MRI Is Improved by Use of a Zinc-Responsive MRI Sensor with Lower Affinity for Zn2+ Ions

André F. Martins, Veronica Clavijo Jordan, Filip Bochner, Sara Chirayil, Namini Paranawithana, Shanrong Zhang, Su Tang Lo, Xiaodong Wen, Piyu Zhao, Michal Neeman, Dean Sherry

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

It has been demonstrated that divalent zinc ions packaged with insulin in β-cell granules can be detected by MRI during glucose-stimulated insulin secretion using a gadolinium-based Zn2+-sensitive agent. This study was designed to evaluate whether a simpler agent design having single Zn2+-sensing moieties but with variable Zn2+ binding affinities might also detect insulin secretion from the pancreas. Using an implanted MR-compatible window designed to hold the pancreas in a fixed position for imaging, we now demonstrate that focally intense "hot spots" can be detected in the tail of the pancreas using these agents after administration of glucose to stimulate insulin secretion. Histological staining of the same tissue verified that the hot spots identified by imaging correspond to clusters of islets, perhaps reflecting first-responder islets that are most responsive to a sudden increase in glucose. A comparison of images obtained when using a high-affinity Zn2+ sensor versus a lower-affinity sensor showed that the lower-affinity sensors produced the best image contrast. An equilibrium model that considers all possible complexes formed between Zn2+, the GdL sensor, and HSA predicts that a GdL sensor with lower affinity for Zn2+ generates a lower background signal from endogenous Zn2+ prior to glucose-stimulated insulin secretion (GSIS) and that the weaker binding affinity agent is more responsive to a further increase in Zn2+ concentration near β-cells after GSIS. These model predictions are consistent with the in vivo imaging observations.

Original languageEnglish (US)
Pages (from-to)17456-17464
Number of pages9
JournalJournal of the American Chemical Society
Volume140
Issue number50
DOIs
StatePublished - Dec 19 2018

Fingerprint

Insulin
Magnetic resonance imaging
Zinc
Pancreas
Glucose
Ions
Imaging techniques
Sensors
Gadolinium
Tail
Tissue
Staining and Labeling

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Imaging Insulin Secretion from Mouse Pancreas by MRI Is Improved by Use of a Zinc-Responsive MRI Sensor with Lower Affinity for Zn2+ Ions. / Martins, André F.; Clavijo Jordan, Veronica; Bochner, Filip; Chirayil, Sara; Paranawithana, Namini; Zhang, Shanrong; Lo, Su Tang; Wen, Xiaodong; Zhao, Piyu; Neeman, Michal; Sherry, Dean.

In: Journal of the American Chemical Society, Vol. 140, No. 50, 19.12.2018, p. 17456-17464.

Research output: Contribution to journalArticle

Martins, AF, Clavijo Jordan, V, Bochner, F, Chirayil, S, Paranawithana, N, Zhang, S, Lo, ST, Wen, X, Zhao, P, Neeman, M & Sherry, D 2018, 'Imaging Insulin Secretion from Mouse Pancreas by MRI Is Improved by Use of a Zinc-Responsive MRI Sensor with Lower Affinity for Zn2+ Ions', Journal of the American Chemical Society, vol. 140, no. 50, pp. 17456-17464. https://doi.org/10.1021/jacs.8b07607
Martins, André F. ; Clavijo Jordan, Veronica ; Bochner, Filip ; Chirayil, Sara ; Paranawithana, Namini ; Zhang, Shanrong ; Lo, Su Tang ; Wen, Xiaodong ; Zhao, Piyu ; Neeman, Michal ; Sherry, Dean. / Imaging Insulin Secretion from Mouse Pancreas by MRI Is Improved by Use of a Zinc-Responsive MRI Sensor with Lower Affinity for Zn2+ Ions. In: Journal of the American Chemical Society. 2018 ; Vol. 140, No. 50. pp. 17456-17464.
@article{a05eeaa8ab9a4840a687aedb3aa50296,
title = "Imaging Insulin Secretion from Mouse Pancreas by MRI Is Improved by Use of a Zinc-Responsive MRI Sensor with Lower Affinity for Zn2+ Ions",
abstract = "It has been demonstrated that divalent zinc ions packaged with insulin in β-cell granules can be detected by MRI during glucose-stimulated insulin secretion using a gadolinium-based Zn2+-sensitive agent. This study was designed to evaluate whether a simpler agent design having single Zn2+-sensing moieties but with variable Zn2+ binding affinities might also detect insulin secretion from the pancreas. Using an implanted MR-compatible window designed to hold the pancreas in a fixed position for imaging, we now demonstrate that focally intense {"}hot spots{"} can be detected in the tail of the pancreas using these agents after administration of glucose to stimulate insulin secretion. Histological staining of the same tissue verified that the hot spots identified by imaging correspond to clusters of islets, perhaps reflecting first-responder islets that are most responsive to a sudden increase in glucose. A comparison of images obtained when using a high-affinity Zn2+ sensor versus a lower-affinity sensor showed that the lower-affinity sensors produced the best image contrast. An equilibrium model that considers all possible complexes formed between Zn2+, the GdL sensor, and HSA predicts that a GdL sensor with lower affinity for Zn2+ generates a lower background signal from endogenous Zn2+ prior to glucose-stimulated insulin secretion (GSIS) and that the weaker binding affinity agent is more responsive to a further increase in Zn2+ concentration near β-cells after GSIS. These model predictions are consistent with the in vivo imaging observations.",
author = "Martins, {Andr{\'e} F.} and {Clavijo Jordan}, Veronica and Filip Bochner and Sara Chirayil and Namini Paranawithana and Shanrong Zhang and Lo, {Su Tang} and Xiaodong Wen and Piyu Zhao and Michal Neeman and Dean Sherry",
year = "2018",
month = "12",
day = "19",
doi = "10.1021/jacs.8b07607",
language = "English (US)",
volume = "140",
pages = "17456--17464",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "50",

}

TY - JOUR

T1 - Imaging Insulin Secretion from Mouse Pancreas by MRI Is Improved by Use of a Zinc-Responsive MRI Sensor with Lower Affinity for Zn2+ Ions

AU - Martins, André F.

AU - Clavijo Jordan, Veronica

AU - Bochner, Filip

AU - Chirayil, Sara

AU - Paranawithana, Namini

AU - Zhang, Shanrong

AU - Lo, Su Tang

AU - Wen, Xiaodong

AU - Zhao, Piyu

AU - Neeman, Michal

AU - Sherry, Dean

PY - 2018/12/19

Y1 - 2018/12/19

N2 - It has been demonstrated that divalent zinc ions packaged with insulin in β-cell granules can be detected by MRI during glucose-stimulated insulin secretion using a gadolinium-based Zn2+-sensitive agent. This study was designed to evaluate whether a simpler agent design having single Zn2+-sensing moieties but with variable Zn2+ binding affinities might also detect insulin secretion from the pancreas. Using an implanted MR-compatible window designed to hold the pancreas in a fixed position for imaging, we now demonstrate that focally intense "hot spots" can be detected in the tail of the pancreas using these agents after administration of glucose to stimulate insulin secretion. Histological staining of the same tissue verified that the hot spots identified by imaging correspond to clusters of islets, perhaps reflecting first-responder islets that are most responsive to a sudden increase in glucose. A comparison of images obtained when using a high-affinity Zn2+ sensor versus a lower-affinity sensor showed that the lower-affinity sensors produced the best image contrast. An equilibrium model that considers all possible complexes formed between Zn2+, the GdL sensor, and HSA predicts that a GdL sensor with lower affinity for Zn2+ generates a lower background signal from endogenous Zn2+ prior to glucose-stimulated insulin secretion (GSIS) and that the weaker binding affinity agent is more responsive to a further increase in Zn2+ concentration near β-cells after GSIS. These model predictions are consistent with the in vivo imaging observations.

AB - It has been demonstrated that divalent zinc ions packaged with insulin in β-cell granules can be detected by MRI during glucose-stimulated insulin secretion using a gadolinium-based Zn2+-sensitive agent. This study was designed to evaluate whether a simpler agent design having single Zn2+-sensing moieties but with variable Zn2+ binding affinities might also detect insulin secretion from the pancreas. Using an implanted MR-compatible window designed to hold the pancreas in a fixed position for imaging, we now demonstrate that focally intense "hot spots" can be detected in the tail of the pancreas using these agents after administration of glucose to stimulate insulin secretion. Histological staining of the same tissue verified that the hot spots identified by imaging correspond to clusters of islets, perhaps reflecting first-responder islets that are most responsive to a sudden increase in glucose. A comparison of images obtained when using a high-affinity Zn2+ sensor versus a lower-affinity sensor showed that the lower-affinity sensors produced the best image contrast. An equilibrium model that considers all possible complexes formed between Zn2+, the GdL sensor, and HSA predicts that a GdL sensor with lower affinity for Zn2+ generates a lower background signal from endogenous Zn2+ prior to glucose-stimulated insulin secretion (GSIS) and that the weaker binding affinity agent is more responsive to a further increase in Zn2+ concentration near β-cells after GSIS. These model predictions are consistent with the in vivo imaging observations.

UR - http://www.scopus.com/inward/record.url?scp=85058778043&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058778043&partnerID=8YFLogxK

U2 - 10.1021/jacs.8b07607

DO - 10.1021/jacs.8b07607

M3 - Article

VL - 140

SP - 17456

EP - 17464

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 50

ER -