Abstract
Insulin resistance contributes to the development of cardio-vascular disease and diabetes. An important but unresolved task is to study the dynamics of insulin resistance in selective cell types of insulin target tissues in vivo. Here we present a novel technique to monitor insulin resistance dynamics non-invasively and longitudinally in vivo in a cell type-specific manner, exemplified by the pancreatic β-cell situated within the micro-organ the islet of Langerhans. We utilize the anterior chamber of the eye (ACE) as a transplantation site and the cornea as a natural body-window to study the development and reversibility of insulin resistance. Engrafted islets in the ACE that express a FoxO1-GFP-based biosensor in their β-cells, report on insulin resistance measured by fluorescence microscopy at single-cell resolution in the living mouse. This technique allows monitoring of cell type specific insulin sensitivity/resistance in real-time in the context of whole body insulin resistance during progression and intervention of disease.
Highlights
ObjectivesThe aim of the present study was to develop and validate an approach allowing studies of the dynamics of insulin resistance in a specific cell type of a multicellular insulin target tissue in the living organism
Based on the different intracellular localization of FoxO1 in response to insulin, i.e. cytosolic in insulin responsive cells and nuclear in insulin resistant cells, which can be resolved by our Anterior Chamber of the Eye (ACE) in vivo imaging platform, we generated a β -cell specific biosensor for insulin resistance (β IRB)
As a proof-of-concept, we analyzed the dynamics of pancreatic β -cell insulin resistance in the leptin-deficient ob/ob mouse in vivo
Summary
The aim of the present study was to develop and validate an approach allowing studies of the dynamics of insulin resistance in a specific cell type of a multicellular insulin target tissue in the living organism
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