Pancreas and liver uptake of new radiolabeled incretins (GLP-1 and Exendin-4) in models of diet-induced and diet-restricted obesity

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2017
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Nuclear Medicine and Biology
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Introduction: Radiolabeled GLP-1 and its analog Exendin-4, have been employed in diabetes and insulinoma. No protocol in conventional Diet-Induced Obesity (DIO), and Diet-Restricted Obesity (DRO), has been identified. Aiming to assess pancreatic beta cell uptake in DIO and DRO, a protocol was designed. Methods: GLP-1-βAla-HYNIC and HYNIC-βAla-Exendin-4 were labeled with technetium-99m. Four Swiss mouse models were adopted: Controls (C), Alloxan Diabetes Controls (ADC), DIO and DRO. Biodistribution and ex-vivo planar imaging were documented. Results: Radiolabeling yield was in the range of 97% and both agents were hydrophilic. Fasting Blood Glucose (FBG) was 79.2 ± 8.2 mg/dl in C, 590.4 ± 23.3 mg/dl in ADC, 234.3 ± 66.7 mg/dl in DIO, and 96.6 ± 9.3 in DRO (p = 0.010). Biodistribution confirmed predominantly urinary excretion. DIO mice exhibited depressed uptake in liver and pancreas, for both radiomarkers, in the range of ADC. DRO only partially restored such values. 99mTc-HYNIC-βAla-Exendin-4 demonstrated better results than GLP-1-βAla-HYNIC-99mTc. Conclusions: 1) Diet-induced obesity remarkably depressed beta cell uptake; 2) Restriction of obesity failed to normalize uptake, despite robust improvement of FBG; 3) HYNIC-βAla-Exendin-4 was the most useful marker; 4) Further studies are recommended in obesity and dieting, including bariatric surgery.

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SEO, DANIELE; FAINTUCH, BLUMA L.; OLIVEIRA, ERICA A. de; FAINTUCH, JOEL. Pancreas and liver uptake of new radiolabeled incretins (GLP-1 and Exendin-4) in models of diet-induced and diet-restricted obesity. Nuclear Medicine and Biology, v. 49, p. 57-64, 2017. DOI: 10.1016/j.nucmedbio.2017.03.002. Disponível em: http://repositorio.ipen.br/handle/123456789/27707. Acesso em: 28 Mar 2024.
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