Functional MR microimaging of pancreatic beta-cell activation.
The increasing incidence of diabetes and the need to further understand its cellular basis has resulted in the development of new diagnostic and therapeutic techniques. Nonetheless, the quest to noninvasively ascertain beta-cell mass and function has not been achieved. Manganese (Mn)-enhanced MRI is presented here as a tool to image beta-cell functionality in cell culture and isolated islets. Similar to calcium, extracellular Mn was taken up by glucose-activated beta-cells resulting in 200% increase in MRI contrast enhancement, versus nonactivated cells. Similarly, glucose-activated islets showed an increase in MRI contrast up to 45%. Although glucose-stimulated Ca influx was depressed in the presence of 100 microM Mn, no significant effect was seen at lower Mn concentrations. Moreover, islets exposed to Mn showed normal glucose sensitivity and insulin secretion. These results demonstrate a link between image contrast enhancement and beta-cell activation in vitro, and provide the basis for future noninvasive in vivo imaging of islet functionality and beta-cell mass.
Gimi
Barjor
B
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD, 21205, USA.
Leoni
Lara
L
Oberholzer
Jose
J
Braun
Mark
M
Avila
Jose
J
Wang
Yong
Y
Desai
Tejal
T
Philipson
Louis H
LH
Magin
Richard L
RL
Roman
Brian B
BB
D000818:Animals; D045744:Cell Line, Tumor; D002469:Cell Separation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D007089:Image Enhancement / Q000379:methods*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000378:metabolism*; D007340:Insulinoma / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology; D016381:Islets of Langerhans Transplantation / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew
D007328:Insulin; D008345:Manganese; D005947:Glucose