Measuring the Pancreatic ß Cell Mass in Vivo with Exendin SPECT during Hyperglycemia and Severe Insulitis.
Mol Pharm
; 16(9): 4024-4030, 2019 09 03.
Article
em En
| MEDLINE
| ID: mdl-31345042
ABSTRACT
OBJECTIVE:
Targeting the glucagon-like peptide-1 receptor with radiolabeled exendin is a very promising method to noninvasively determine the ß cell mass in the pancreas, which is needed to unravel the pathophysiology of type 1 and type 2 diabetes. The present study aimed to explore the effects of both hyperglycemia and insulitis on the uptake of exendin in a spontaneous type 1 diabetes mouse model, nonobese diabetic (NOD) mice.METHODS:
NOD mice (n = 75, 7-21 weeks old) were injected intravenously with [111In]In-DTPA-exendin-3, and single-photon emission computed tomography (SPECT) images were acquired 1 h pi. The pancreatic accumulation of [111In]In-DTPA-exendin-3 was quantified in vivo using SPECT and by ex vivo counting and correlated to the ß cell mass (BCM). The influence of insulitis and hyperglycemia on the exendin uptake was assessed.RESULTS:
The pancreas could be visualized longitudinally using SPECT. A linear correlation was found between the BCM (%) and pancreatic uptake (%ID/g) as measured by ex vivo counting (Pearson r = 0.64, p < 0.001), which was not affected by either insulitis (Pearson r = 0.66, p = 0.83) or hyperglycemia (Pearson r = 0.57, p = 0.51). Biodistribution and ex vivo autoradiography revealed remaining [111In]In-DTPA-exendin-3 uptake in the pancreas despite total ablation of BCM.CONCLUSIONS:
Despite hyperglycemia and severe insulitis, we have found a good correlation between BCM and pancreatic exendin uptake, even in a suboptimal model with relatively high background activity.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Tomografia Computadorizada de Emissão de Fóton Único
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Diabetes Mellitus Tipo 1
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Células Secretoras de Insulina
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Hiperglicemia
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article