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

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-beta Ala-HYNIC and HYNIC-beta Ala-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. Tc-99m-HYNIC-beta Ala-Exendin-4 demonstrated better results than GLP-1-beta Ala-HYNIC-Tc-99m. 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-beta Ala-Exendin-4 was the most useful marker; 4) Further studies are recommended in obesity and dieting, including bariatric surgery. (C) 2017 Elsevier Inc. All rights reserved.