GPR44 as a Target for Imaging Pancreatic Beta-Cell Mass

Eriksson, Olof

doi:10.1007/s11892-019-1164-z

Cited by 14 publications

(13 citation statements)

References 37 publications

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“…Therefore, the various molecules whose expression is observed specifically in b cells have been explored, and those ligands, substrates, and antibodies have been investigated as putative probes for b-cell imaging. To date, sulfonylurea receptor 1 (SUR1) (40,41), glucose transporter 2 (42), voltage-dependent calcium channel (43), G protein-coupled receptor 44 (GPR44) (44,45), D2 and D3 dopamine receptors (46,47), serotonergic system (48-51), vesicular monoamine transporter 2 (VMAT2) (52,53), and GLP-1 receptor (GLP-1R) (54, 55) have been reported as potential probe targets (Figure 2) (56).…”

Section: Exploration Of Ideal Probe Targets In In Vivo B-cell Imagingmentioning

confidence: 99%

Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

2021

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Pancreatic beta (β)-cell dysfunction and reduced mass play a central role in the development and progression of diabetes mellitus. Conventional histological β-cell mass (BCM) analysis is invasive and limited to cross-sectional observations in a restricted sampling area. However, the non-invasive evaluation of BCM remains elusive, and practical in vivo and clinical techniques for β-cell-specific imaging are yet to be established. The lack of such techniques hampers a deeper understanding of the pathophysiological role of BCM in diabetes, the implementation of personalized BCM-based diabetes management, and the development of antidiabetic therapies targeting BCM preservation and restoration. Nuclear medical techniques have recently triggered a major leap in this field. In particular, radioisotope-labeled probes using exendin peptides that include glucagon-like peptide-1 receptor (GLP-1R) agonist and antagonist have been employed in positron emission tomography and single-photon emission computed tomography. These probes have demonstrated high specificity to β cells and provide clear images accurately showing uptake in the pancreas and transplanted islets in preclinical in vivo and clinical studies. One of these probes, 111indium-labeled exendin-4 derivative ([Lys12(111In-BnDTPA-Ahx)]exendin-4), has captured the longitudinal changes in BCM during the development and progression of diabetes and under antidiabetic therapies in various mouse models of type 1 and type 2 diabetes mellitus. GLP-1R-targeted imaging is therefore a promising tool for non-invasive BCM evaluation. This review focuses on recent advances in non-invasive in vivo β-cell imaging for BCM evaluation in the field of diabetes; in particular, the exendin-based GLP-1R-targeted nuclear medicine techniques.

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Section: Exploration Of Ideal Probe Targets In In Vivo B-cell Imagingmentioning

confidence: 99%

Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

2021

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“…During the last decade, several putative beta cell-specific probes have been identified, including monoclonal antibodies (mAbs) [ 42 , 43 ], short or fragments of antibodies [ 44 , 45 ], peptides [ 46 , 47 , 48 ], small molecules such as metabolites [ 49 , 50 , 51 ], and ion-binding probes [ 52 , 53 ]. The different existing tracers have been recently and comprehensively reviewed [ 54 ] and will not be further discussed here.…”

Section: Bcm Probes Presently Under Clinical Investigationmentioning

confidence: 99%

Beta Cell Imaging—From Pre-Clinical Validation to First in Man Testing

Demine

Schulte

Territo

et al. 2020

IJMS

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There are presently no reliable ways to quantify human pancreatic beta cell mass (BCM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. Furthermore, the lack of beta cell imaging hampers the evaluation of the impact of new drugs aiming to prevent beta cell loss or to restore BCM in diabetes. We presently discuss the potential value of BCM determination as a cornerstone for individualized therapies in diabetes, describe the presently available probes for human BCM evaluation, and discuss our approach for the discovery of novel beta cell biomarkers, based on the determination of specific splice variants present in human beta cells. This has already led to the identification of DPP6 and FXYD2ga as two promising targets for human BCM imaging, and is followed by a discussion of potential safety issues, the role for radiochemistry in the improvement of BCM imaging, and concludes with an overview of the different steps from pre-clinical validation to a first-in-man trial for novel tracers.

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“…In addition to optical methods, several other imaging modalities have been used to image b-cell mass (16)(17) and function (18,19) in vivo in rodents. Although the rodent model is widely used, there are technical challenges in imaging the rodent pancreas because, unlike the human pancreas, the rodent pancreas is an irregular-shaped thin layer of soft tissue spread throughout the upper abdomen (16).…”

Section: Introductionmentioning

confidence: 99%

Imaging β-Cell Function Using a Zinc-Responsive MRI Contrast Agent May Identify First Responder Islets

et al. 2022

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An imaging method for detecting β-cell function in real-time in the rodent pancreas could provide new insights into the biological mechanisms involving loss of β-cell function during development of type 2 diabetes and for testing of new drugs designed to modulate insulin secretion. In this study, we used a zinc-responsive MRI contrast agent and an optimized 2D MRI method to show that glucose stimulated insulin and zinc secretion can be detected as functionally active “hot spots” in the tail of the rat pancreas. A comparison of functional images with histological markers show that insulin and zinc secretion does not occur uniformly among all pancreatic islets but rather that some islets respond rapidly to an increase in glucose while others remain silent. Zinc and insulin secretion was shown to be altered in streptozotocin and exenatide treated rats thereby verifying that this simple MRI technique is responsive to changes in β-cell function.

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GPR44 as a Target for Imaging Pancreatic Beta-Cell Mass

Cited by 14 publications

References 37 publications

Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

Beta Cell Imaging—From Pre-Clinical Validation to First in Man Testing

Imaging β-Cell Function Using a Zinc-Responsive MRI Contrast Agent May Identify First Responder Islets

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