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

Seo, D.; Faintuch, Bluma Linkowski; Oliveira, Érica Aparecida de; Faintuch, Joel

doi:10.1016/j.nucmedbio.2017.03.002

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…GLP-1 receptor was found in nerves that innervate hepatocytes [172], but their presence on human liver or hepatocytes is debated as found by some [169,170] but not others [173,174]. A recent study that used incretins (GLP-1 and Exendin-4) radiolabeled with technetium-99m showed that the tracer was highly taken up both by the liver and the pancreas and that the uptake was reduced in both organs after diet-induced obesity (DIO), similarly to alloxan diabetes controls [175].…”

Section: Effect Of Glp-1 and Glp-1ra On Hepatic Glucose And Lipid Metmentioning

confidence: 99%

Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH

Svegliati‐Baroni

Patrı́cio

Lioci

et al. 2020

IJMS

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Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease worldwide. Due to its association with obesity and diabetes and the fall in hepatitis C virus morbidity, cirrhosis in NAFLD is becoming the most frequent indication to liver transplantation, but the pathogenetic mechanisms are still not completely understood. The so-called gut-liver axis has gained enormous interest when data showed that its alteration can lead to NAFLD development and might favor the occurrence of non-alcoholic steatohepatitis (NASH). Moreover, several therapeutic approaches targeting the gut-pancreas-liver axis, e.g., incretins, showed promising results in NASH treatment. In this review, we describe the role of incretin hormones in NAFLD/NASH pathogenesis and treatment and how metagenomic/metabolomic alterations in the gut microbiota can lead to NASH in the presence of gut barrier modifications favoring the passage of bacteria or bacterial products in the portal circulation, i.e., bacterial translocation.

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Section: Effect Of Glp-1 and Glp-1ra On Hepatic Glucose And Lipid Metmentioning

confidence: 99%

Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH

Svegliati‐Baroni

Patrı́cio

Lioci

et al. 2020

IJMS

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“…Two analogues of [Lys 40 (Ahx-HYNIC- 99m Tc/EDDA])NH 2 ]-exendin-4 containing either methionine or norleucine at position 14 demonstrated similar biodistribution with blockable uptake in GLP-1R positive organs such as lung, pancreas and stomach in normal rats 86. 99m Tc-HYNIC-β-Ala-Exedin4 was successfully used to monitor the BCM in mouse model of diet-induced obesity (DIO) and diet-restricted obesity (DRO) wherein DIO considerably reduced the beta cell uptake and DRO failed to normalize the uptake 91. A GMP compliant freeze-dried kit for the preparation of 99m Tc-EDDA/HYNIC)-exendin(9-39) was developed and validated for the clinical use in diagnosis of insulinomas 92.…”

Section: Imaging Agents: Chemistry and Pre-clinical Evaluationmentioning

confidence: 98%

Advances in GLP-1 receptor targeting radiolabeled agent development and prospective of theranostics

Velikyan

Eriksson

2020

Theranostics

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In the light of theranostics/radiotheranostics and prospective of personalized medicine in diabetes and oncology, this review presents prior and current advances in the development of radiolabeled imaging and radiotherapeutic exendin-based agents targeting glucagon-like peptide-1 receptor. The review covers chemistry, preclinical, and clinical evaluation. Such critical aspects as structure-activity-relationship, stability, physiological potency, kidney uptake, and dosimetry are discussed.

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“…67 A recent approach based on radiolabeled GLP-1/exendin-4 found a high uptake in pancreas and liver in mice which was reduced in the diet-induces obesity phenotype. 93 In addition, evidence was provided from hepatocyte cell lines and primary hepatocytes that GLP-1 RAs reduce triglyceride content by modulation of elements of the insulin signaling pathway as well as by enhancing fatty acid oxidation and reducing lipogenesis. 67 91 94 95 Animal models also suggested that GLP-1 RAs may reduce inflammation through mechanisms that are—at least in part—independent of body weight reduction.…”

Section: Treating People With Nash and Type 2 Diabetesmentioning

confidence: 99%

Novel Antidiabetic Strategies and Diabetologists' Views in Nonalcoholic Steatohepatitis

2021

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Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide with high prevalence, especially in individuals with obesity and type 2 diabetes. Among individuals with type 2 diabetes, the severe insulin resistant subgroup has the greatest risk of NAFLD, likely due to dysfunctional adipose tissue mass but also genetic factors, and may progress earlier to inflammatory and profibrotic nonalcoholic steatohepatitis (NASH). NASH has been associated with increased liver-related as well as cardiovascular morbidity and mortality. International diabetes associations recommend certain screening and treatment strategies for NASH in type 2 diabetes, which, however, bear several limitations such as lack of accurate noninvasive diagnostic tools and targeted treatments. Currently, antihyperglycemic drug concepts based on glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors offer metabolic as well as cardiorenal benefits and provide treatment options for both hyperglycemia and NASH in type 2 diabetes.

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

Cited by 5 publications

References 38 publications

Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH

Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH

Advances in GLP-1 receptor targeting radiolabeled agent development and prospective of theranostics

Novel Antidiabetic Strategies and Diabetologists' Views in Nonalcoholic Steatohepatitis

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