Journal article
Radiomanganese PET Detects Changes in Functional β-Cell Mass in Mouse Models of Diabetes
Diabetes (New York, N.Y.), Vol.66(8), pp.2163-2174
08/01/2017
DOI: 10.2337/db16-1285
PMCID: PMC5521871
PMID: 28515126
Abstract
The noninvasive measurement of functional β-cell mass would be clinically valuable for monitoring the progression of type 1 and type 2 diabetes as well as the viability of transplanted insulin-producing cells. Although previous work using MRI has shown promise for functional β-cell mass determination through voltage-dependent Ca
channel (VDCC)-mediated internalization of Mn
, the clinical utility of this technique is limited by the cytotoxic levels of the Mn
contrast agent. Here, we show that positron emission tomography (PET) is advantageous for determining functional β-cell mass using
Mn
(
: 5.6 days). We investigated the whole-body distribution of
Mn
in healthy adult mice by dynamic and static PET imaging. Pancreatic VDCC uptake of
Mn
was successfully manipulated pharmacologically in vitro and in vivo using glucose, nifedipine (VDCC blocker), the sulfonylureas tolbutamide and glibenclamide (K
channel blockers), and diazoxide (K
channel opener). In a mouse model of streptozotocin-induced type 1 diabetes,
Mn
uptake in the pancreas was distinguished from healthy controls in parallel with classic histological quantification of β-cell mass from pancreatic sections.
Mn
-PET also reported the expected increase in functional β-cell mass in the
/
model of pretype 2 diabetes, a result corroborated by histological β-cell mass measurements and live-cell imaging of β-cell Ca
oscillations. These results indicate that
Mn
-PET is a sensitive new tool for the noninvasive assessment of functional β-cell mass.
Details
- Title: Subtitle
- Radiomanganese PET Detects Changes in Functional β-Cell Mass in Mouse Models of Diabetes
- Creators
- Reinier Hernandez - University of Wisconsin–MadisonStephen A Graves - University of Wisconsin–MadisonTrillian Gregg - University of Wisconsin–MadisonHalena R VanDeusen - University of Wisconsin–MadisonRachel J Fenske - University of Wisconsin–MadisonHaley N Wienkes - University of Wisconsin–MadisonChristopher G England - University of Wisconsin–MadisonHector F Valdovinos - University of Wisconsin–MadisonJustin J Jeffery - University of Wisconsin Carbone Cancer CenterTodd E Barnhart - University of Wisconsin–MadisonGregory W Severin - Technical University of DenmarkRobert J Nickles - University of Wisconsin–MadisonMichelle E Kimple - University of Wisconsin–MadisonMatthew J Merrins - University of Wisconsin–MadisonWeibo Cai - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.66(8), pp.2163-2174
- DOI
- 10.2337/db16-1285
- PMID
- 28515126
- PMCID
- PMC5521871
- NLM abbreviation
- Diabetes
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Grant note
- T32 GM008293 / NIGMS NIH HHS T32 GM008349 / NIGMS NIH HHS F31 DK109698 / NIDDK NIH HHS T32 CA009206 / NCI NIH HHS R01 DK102598 / NIDDK NIH HHS R01 CA169365 / NCI NIH HHS P30 CA014520 / NCI NIH HHS R01 EB021336 / NIBIB NIH HHS K01 DK101683 / NIDDK NIH HHS R01 DK113103 / NIDDK NIH HHS R21 AG050135 / NIA NIH HHS
- Language
- English
- Date published
- 08/01/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984383884302771
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