title: Manganese-mediated MRI signals correlate with functional β-cell mass during diabetes progression.
abstract: Diabetes diagnostic therapy and research would strongly benefit from noninvasive accurate imaging of the functional β-cells in the pancreas. Here, we developed an analysis of functional β-cell mass (BCM) by measuring manganese (Mn(2+)) uptake kinetics into glucose-stimulated β-cells by T1-weighted in vivo Mn(2+)-mediated MRI (MnMRI) in C57Bl/6J mice. Weekly MRI analysis during the diabetes progression in mice fed a high-fat/high-sucrose diet (HFD) showed increased Mn(2+)-signals in the pancreas of the HFD-fed mice during the compensation phase, when glucose tolerance and glucose-stimulated insulin secretion (GSIS) were improved and BCM was increased compared with normal diet-fed mice. The increased signal was only transient; from the 4th week on, MRI signals decreased significantly in the HFD group, and the reduced MRI signal in HFD mice persisted over the whole 12-week experimental period, which again correlated with both impaired glucose tolerance and GSIS, although BCM remained unchanged. Rapid and significantly decreased MRI signals were confirmed in diabetic mice after streptozotocin (STZ) injection. No long-term effects of Mn(2+) on glucose tolerance were observed. Our optimized MnMRI protocol fulfills the requirements of noninvasive MRI analysis and detects already small changes in the functional BCM.
authors: Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany.
authors: Anke
authors: A
authors: Meyer
authors: Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany.
authors: Katharina
authors: K
authors: Stolz
authors: In-vivo-MR, University of Bremen, Bremen, Germany.
authors: Wolfgang
authors: W
authors: Dreher
authors: Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany.
authors: Jennifer
authors: J
authors: Bergemann
authors: In-vivo-MR, University of Bremen, Bremen, Germany.
authors: Vani
authors: V
authors: Holebasavanahalli Thimmashetty
authors: Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany.
authors: Navina
authors: N
authors: Lueschen
authors: Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany.
authors: Zahra
authors: Z
authors: Azizi
authors: Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany.
authors: Vrushali
authors: V
authors: Khobragade
authors: Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany kmaedler@uni-bremen.de.
authors: Kathrin
authors: K
authors: Maedler
authors: In-vivo-MR, University of Bremen, Bremen, Germany.
authors: Ekkehard
authors: E
authors: Kuestermann
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008345:Manganese / Q000378:metabolism*; D051379:Mice
chemical_list: D008345:Manganese