Multifunctional in vivo imaging of pancreatic islets during diabetes development

Abstract

Pancreatic islet dysfunction leading to insufficient glucose-stimulated insulin secretion triggers the clinical onset of diabetes. How islet dysfunction develops is not well understood at the cellular level, partly owing to the lack of approaches to study single islets longitudinally in vivo. Here, we present a noninvasive, high-resolution system to quantitatively image real-time glucose metabolism from single islets in vivo, currently not available with any other method. In addition, this multifunctional system simultaneously reports islet function, proliferation, vasculature and macrophage infiltration in vivo from the same set of images. Applying our method to a longitudinal high-fat diet study revealed changes in islet function as well as alternations in islet microenvironment. More importantly, this label-free system enabled us to image real-time glucose metabolism directly from single human islets in vivo for the first time, opening the door to noninvasive longitudinal in vivo studies of healthy and diabetic human islets.

Adipsin preserves beta cells in diabetic mice and associates with protection from type 2 diabetes in humans

“…Islet transplantation and in vivo imaging have been described previously 12 . In brief, mouse islets from B6 WT and db/db mice were isolated the day before transplantation and cultured overnight in RPMI 1640 with 10% FBS.…”

Intraocular in vivo imaging of pancreatic islet cell physiology/pathology

“…These and other studies demonstrate the potential of islet intrinsic parameters for the study of islet/beta cell function and survival, namely islet volume, morphology of intra-islet vasculature including vessel diameter and blood vessel integrity (leakage), islet backscatter signal indicating islet integrity and beta cell insulin content, macrophage infiltration, collagen accumulation, cell death, and glucose metabolism indicated by NAD(P)H levels [6] , [7] , [29] , [30] , [31] , [32] , [33] .…”

Mesoscopic 3D imaging of pancreatic cancer and Langerhans islets based on tissue autofluorescence

“…Further, the possibility to study the individual vessel trajectories in relation to tumour volume may www.nature.com/scientificreports/ be highly useful to increase our understanding of PDAC vascularization and how to overcome problems related to drug delivery in these cancers. Although it has been described that islets grafted to the anterior chamber of the eye display AF properties up to 600 nm in vivo 31 , the high signal to noise ratio between islet AF and surrounding pancreatic tissue in the red to the NIR part of the spectrum has to the best of our knowledge not been described previously. In our study, we observed droplet like regions of islet AF over a broad range of the spectrum (excitation maxima tested between 480 and 710 nm).…”