Multifunctional in vivo imaging of pancreatic islets during diabetes development.
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.
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA.
Ge
G
Li
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA.
Binlin
B
Wu
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA.
Meliza G
MG
Ward
Department of Surgery, Weill Cornell Medical College, New York, NY 10065, USA.
Angie C N
AC
Chong
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA.
Sushmita
S
Mukherjee
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA Department of Surgery, Weill Cornell Medical College, New York, NY 10065, USA mhao@med.cornell.edu shc2034@med.cornell.edu.
Shuibing
S
Chen
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA mhao@med.cornell.edu shc2034@med.cornell.edu.
Mingming
0000-0003-4677-5111
M
Hao
D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003199:Computer Systems; D003920:Diabetes Mellitus / Q000473:pathology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005453:Fluorescence; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D021621:Imaging, Three-Dimensional; D007274:Injections, Intraperitoneal; D007515:Islets of Langerhans / Q000098:blood supply / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice
D003094:Collagen; D005947:Glucose
Diabetes; Glucose metabolism; In vivo imaging; Multiphoton microscopy; NAD(P)H; Pancreatic islets