Dataset Information

Feasibility of amylin imaging in pancreatic islets with β-amyloid imaging probes.

ABSTRACT: Islet amyloid deposition composed of amylin aggregates is regarded as one of the hallmarks of type 2 diabetes mellitus (T2DM). For the diagnosis of T2DM, several nuclear medical imaging probes have been developed. However, there have been no reports regarding the development of imaging probes targeting amylin. In this report, we investigated the feasibility of amylin imaging using [(125)I]IPBF as one of the model compounds of β-amyloid (Aβ) imaging probes. In in vitro experiments, [(125)I]IPBF exhibited high binding affinity for amylin aggregates (Kd = 8.31 nM). Moreover, autoradiographic images showed that [(125)I]IPBF specifically bound to islet amyloid composed of amylin. These results suggest the potential application of Aβ imaging probes to amylin imaging. In addition, [(125)I]IPBF is one of the promising lead compounds for amylin imaging, and further structural optimization based on [(125)I]IPBF may lead to useful tracers for the in vivo imaging of islet amyloids in the pancreas.

SUBMITTER: Yoshimura M

PROVIDER: S-EPMC4139942 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Feasibility of amylin imaging in pancreatic islets with β-amyloid imaging probes.

Yoshimura Masashi M Ono Masahiro M Watanabe Hiroyuki H Kimura Hiroyuki H Saji Hideo H

Scientific reports 20140821

Islet amyloid deposition composed of amylin aggregates is regarded as one of the hallmarks of type 2 diabetes mellitus (T2DM). For the diagnosis of T2DM, several nuclear medical imaging probes have been developed. However, there have been no reports regarding the development of imaging probes targeting amylin. In this report, we investigated the feasibility of amylin imaging using [(125)I]IPBF as one of the model compounds of β-amyloid (Aβ) imaging probes. In in vitro experiments, [(125)I]IPBF e ...[more]

PMID: 25142178

Similar Datasets

Project description:BackgroundNeuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer's disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors.MethodsThe presence of dimeric components of the amylin receptor (calcitonin receptor and receptor activity modifying protein 3) were first immunohistochemically identified on microglia. Purified human fetal microglial (HFM) cultures were incubated with an in vivo microglial marker, DyLight 594-conjugated tomato lectin, and loaded with the membrane-permeant green fluorescent dye, Fluo-8L-AM for measurements of intracellular calcium [Ca2+]i. HFM and BV-2 cells were primed with lipopolysaccharide and then exposed to either human amylin or soluble oligomeric Aβ1-42 prior to treatment with and without the amylin receptor antagonist, AC253. Changes in the inflammasome complex, NLRP3 and caspase-1, were examined in treated cell cultures with Western blot and fluorometric assays. RT-PCR measurements were performed to assess cytokine release. Finally, in vivo studies were performed in transgenic mouse model of AD (5xFAD) to examine the effects of systemic administration of AC253 on markers of neuroinflammation in the brain.ResultsAcute applications of human amylin or Aβ1-42 resulted in an increase in [Ca2+]i that could be blocked by the amylin receptor antagonist, AC253. Activation of the NLRP3 and caspase-1 and subsequent release of cytokines, TNFα and IL-1β, was diminished by AC253 pretreatment of HFMs and BV2 cells. In vivo, intraperitoneal administration of AC253 resulted in a reduction in microglial markers (Iba-1 and CD68), caspase-1, TNFα, and IL-1β. These reductions in inflammatory markers were accompanied by reduction in amyloid plaque and size in the brains of 5xFAD mice compared to controls.ConclusionMicroglial amylin receptors mediate Aβ-evoked inflammation, and amylin receptor antagonists therefore offer an attractive therapeutic target for intervention in AD.

Dataset Information

Feasibility of amylin imaging in pancreatic islets with β-amyloid imaging probes.

Publications

Feasibility of amylin imaging in pancreatic islets with β-amyloid imaging probes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets