Non-invasive cell type selective in vivo monitoring of insulin resistance dynamics

Sci Rep. 2016 Feb 22:6:21448. doi: 10.1038/srep21448.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage / genetics*
  • Cell Tracking / methods*
  • Cornea / metabolism
  • Cornea / pathology
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / genetics*
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Insulin-Secreting Cells / transplantation
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Mice
  • Microscopy, Fluorescence
  • Single-Cell Analysis

Substances

  • Insulin