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X Zheng,
X Wang,
Z Ma,
V Gupta Sunkari,
I Botusan, T Takeda,
A Björklund,
M Inoue,
S-B Catrina,
K Brismar,
L Poellinger,
T S Pereira
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ABSTRACT: The success of pancreatic β-cells transplantation to treat type 1 diabetes has been hindered by massive β-cell dysfunction and loss of β-cells that follows the procedure. Hypoxia-mediated cell death has been considered one of the main difficulties that must be overcome for transplantation to be regarded as a reliable therapy. Here we have investigated the mechanisms underlying β-cell death in response to hypoxia (1% O(2)). Our studies show that mouse insulinoma cell line 6 (Min6) cells undergo apoptosis with caspase-3 activation occurring as early as 2 h following exposure to hypoxia. Hypoxia induces endoplasmic reticulum stress in Min6 cells leading to activation of the three branches of the unfolded protein response pathway. In response to hypoxia the pro-apoptotic transcription factor C/EBP homologous protein (CHOP) is upregulated. The important role of CHOP in the apoptotic process was highlighted by the rescue of Min6 cells from hypoxia-mediated apoptosis observed in CHOP-knockdown cells. Culturing isolated pancreatic mouse islets at normoxia showed intracellular hypoxia with accumulation of hypoxia-inducible factor-1α and upregulation of CHOP, the latter one occurring as early as 4 h after isolation. Finally, we observed that pancreatic islets of type 2 db/db diabetic mice were more hypoxic than their counterpart in normoglycemic animals. This finding indicates that hypoxia-mediated apoptosis may occur in type 2 diabetes.
Cell Death & Disease 01/2012; 3:e322. · 5.33 Impact Factor
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ABSTRACT: Using magnetoencephalography (MEG) and a taste stimulator with rapid-rise time, we previously located the primary gustatory area in the human cerebral cortex and also investigated the relation between the onset latency of the gustatory-evoked magnetic fields (GEM) and reaction times (RT) in different taste qualities. In the present study, we investigated the temporal process from receptors to the higher brain in taste detection based on the results of the GEM and RT of different tastes. We used 100 mM, 300 mM and 1 M NaCl and 3 mM saccharine. The duration of each stimulus was 400 ms. The interstimulus interval was approximately 30 s. The temperature of both taste solution and deionized water was maintained the same as that of the tongue. Four subjects participated in this experiment. The 64-channel whole-head SQUID system (CTF Systems Inc., Canada) was used to measure GEM. The sampling rate was 250 Hz, and the low-pass filter was 40 Hz. In each subject, GEM and RT to a given taste were measured separately by applying 40 trials of stimulation. After each trial of both measurements, subjects showed a perceived intensity by using their fingers. In the GEM study, the trials contaminated with eye movements were rejected and the remaining trials were averaged. Averaged GEM were super-imposed on the same sheet with all 64 channels to measure the onset latency of GEM from the stimulus onset. RT and onset latencies of GEM were longer for saccharine than NaCl, and the value of RT minus the onset latency of GEM from RT, presumably indicating the time for higher brain process plus motor process, did not differ between 3 mM saccharine and 1 M NaCl. With increased concentrations of NaCl, RT became shorter, but onset latencies of GEM remained constant. Sweet taste took a longer time than salty taste at receptor process including the time for diffusion to receptors.
Annals of the New York Academy of Sciences 12/1998; 855:493-7. · 3.15 Impact Factor
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ABSTRACT: Magnetic fields (MFs) from gustatory stimulation with 1 M NaCl and 3 mM saccharin were recorded from the human brain by using a whole-cortex SQUID system. The averaged onset latency of MFs was 93 ms for NaCl and 172 ms for saccharin and no response was obtained for water. A high correlation coefficient was noted between the difference of onset MFs latencies in two tastants and that of behavioral reaction times, and responses to saccharin were delayed or abolished after treatment of a subject's tongue with a sweet-suppressing agent. This finding indicates that the MFs obtained were caused by gustatory stimulation. By plotting the estimated current dipole on the magnetic resonance image, we could locate the primary gustatory area at the transition area between the operculum and insula, as reported in macaque monkeys.
Neuroscience Letters 08/1996; 212(3):155-8. · 2.11 Impact Factor
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Electroencephalography and clinical neurophysiology. Supplement 02/1996; 47:133-41.
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Electroencephalography and clinical neurophysiology. Supplement 02/1996; 47:283-91.
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Electroencephalography and clinical neurophysiology. Supplement 02/1996; 47:121-7.
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Electroencephalography and clinical neurophysiology. Supplement 02/1996; 47:449-57.
