Radiomanganese PET Detects Changes in Functional ß-Cell Mass in Mouse Models of Diabetes.
Diabetes
; 66(8): 2163-2174, 2017 08.
Article
em En
| MEDLINE
| ID: mdl-28515126
ABSTRACT
The noninvasive measurement of functional ß-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 ß-cell mass determination through voltage-dependent Ca2+ channel (VDCC)-mediated internalization of Mn2+, the clinical utility of this technique is limited by the cytotoxic levels of the Mn2+ contrast agent. Here, we show that positron emission tomography (PET) is advantageous for determining functional ß-cell mass using 52Mn2+ (t1/2 5.6 days). We investigated the whole-body distribution of 52Mn2+ in healthy adult mice by dynamic and static PET imaging. Pancreatic VDCC uptake of 52Mn2+ was successfully manipulated pharmacologically in vitro and in vivo using glucose, nifedipine (VDCC blocker), the sulfonylureas tolbutamide and glibenclamide (KATP channel blockers), and diazoxide (KATP channel opener). In a mouse model of streptozotocin-induced type 1 diabetes, 52Mn2+ uptake in the pancreas was distinguished from healthy controls in parallel with classic histological quantification of ß-cell mass from pancreatic sections. 52Mn2+-PET also reported the expected increase in functional ß-cell mass in the ob/ob model of pretype 2 diabetes, a result corroborated by histological ß-cell mass measurements and live-cell imaging of ß-cell Ca2+ oscillations. These results indicate that 52Mn2+-PET is a sensitive new tool for the noninvasive assessment of functional ß-cell mass.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos de Manganês
/
Compostos Radiofarmacêuticos
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Tomografia por Emissão de Pósitrons
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Diabetes Mellitus Experimental
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Células Secretoras de Insulina
Tipo de estudo:
Evaluation_studies
/
Observational_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article