Wolfram syndrome, an autosomal recessive disorder associated with diabetes and optic atrophy, is caused by mutations in the WFS1 gene encoding wolframin, an endoplasmic reticulum membrane protein. Recent development o...Wolfram syndrome, an autosomal recessive disorder associated with diabetes and optic atrophy, is caused by mutations in the WFS1 gene encoding wolframin, an endoplasmic reticulum membrane protein. Recent development of incretin-based drugs demonstrates promising outcomes for treatment of diabetes mellitus. The aim of this study is to evaluate whether dipeptidyl peptidase-4 inhibition is effective for treating endoplasmic reticulum stress-mediated β-dell failure and impaired glucose tolerance in WFS1-deficient mice (Wfs1-/-). Wfs1-/- mice were orally administrated with vildagliptin (50 mg/kg), a dipeptidyl peptidase-4 inhibitor, twice a day for 4 weeks. The pancreases of these mice were subjected to morphological and biochemical analyses and their glucose tolerance was studied. Electron microscopic studies revealed that vildagliptin reduced number of β-cell containing swollen endoplasmic reticulum in Wfs1-/-?mice. Vildagliptin treatment increased pancreatic insulin content by 30% in Wfs1-/- mice. Oral and intraperitoneal glucose tolerance tests showed improved glucose tolerance in vildagliptin-treated Wfs1-/- mice with increased glucose responsiveness of insulin secretion as compared with vehicle-treated mutant mice. These effects by dipeptidyl peptidase-4 inhibition were partly prevented by glucagon-like peptide-1 receptor blockade. These findings provide evidence that activation of the incretin system by dipeptidyl peptidase-4 inhibition plays a protective role against β-cell failure in wolframin-deficiency. Our data suggest that diabetes in patients affected with Wolfram syndrome could be treated by incretin-based drugs. Furthermore, since WFS1 dysfunction could be involved in common forms of type 2 diabetes mellitus, our results strengthen the mechanistic rational of using this drug for the disease.展开更多
Today, wireless LAN (IEEE802.11g/n) has been the dominant wireless network that can provide high data rates in a limited coverage area. While emerging mobile WiMAX (IEEE802.16e) can provide a wireless broadband access...Today, wireless LAN (IEEE802.11g/n) has been the dominant wireless network that can provide high data rates in a limited coverage area. While emerging mobile WiMAX (IEEE802.16e) can provide a wireless broadband access to mobile users in a wide coverage area. These two different technolgies will co-exist while complementing each other in some regions, hence, a mobile node (MN) with dual interfaces traverses and executes many handovers (HOs) between 802.11g and 802.16e. Meanwhile, there is a huge demand for Voice over IP (VoIP) service over wireless networks. However, VoIP is a delay and loss sensitive application, hence, VoIP session is more likely to be deteriorated during HO between 802.11g and 802.16e. In order to maintain quality of VoIP session during HO, we proposed Vertical Handover Management (VHM) for VoIP session that focuses on HO initiation and decision strategy according to the wireless link condition and congestion state of wireless networks. The VHM exploits request to send (RTS) retries and round trip time (RTT) between an MN and an access point in an 802.11g interface as well as a carrier to interference noise ration (CINR) level and MN’s queue length of an 802.16e interface as HO triggers. We then conducted simulation experiments to evaluate the effectiveness of our proposed VHM using QualNet 4.5. Our simulation results show that our proposed VHM can preserve the quality of VoIP session during such HOs.展开更多
文摘Wolfram syndrome, an autosomal recessive disorder associated with diabetes and optic atrophy, is caused by mutations in the WFS1 gene encoding wolframin, an endoplasmic reticulum membrane protein. Recent development of incretin-based drugs demonstrates promising outcomes for treatment of diabetes mellitus. The aim of this study is to evaluate whether dipeptidyl peptidase-4 inhibition is effective for treating endoplasmic reticulum stress-mediated β-dell failure and impaired glucose tolerance in WFS1-deficient mice (Wfs1-/-). Wfs1-/- mice were orally administrated with vildagliptin (50 mg/kg), a dipeptidyl peptidase-4 inhibitor, twice a day for 4 weeks. The pancreases of these mice were subjected to morphological and biochemical analyses and their glucose tolerance was studied. Electron microscopic studies revealed that vildagliptin reduced number of β-cell containing swollen endoplasmic reticulum in Wfs1-/-?mice. Vildagliptin treatment increased pancreatic insulin content by 30% in Wfs1-/- mice. Oral and intraperitoneal glucose tolerance tests showed improved glucose tolerance in vildagliptin-treated Wfs1-/- mice with increased glucose responsiveness of insulin secretion as compared with vehicle-treated mutant mice. These effects by dipeptidyl peptidase-4 inhibition were partly prevented by glucagon-like peptide-1 receptor blockade. These findings provide evidence that activation of the incretin system by dipeptidyl peptidase-4 inhibition plays a protective role against β-cell failure in wolframin-deficiency. Our data suggest that diabetes in patients affected with Wolfram syndrome could be treated by incretin-based drugs. Furthermore, since WFS1 dysfunction could be involved in common forms of type 2 diabetes mellitus, our results strengthen the mechanistic rational of using this drug for the disease.
文摘Today, wireless LAN (IEEE802.11g/n) has been the dominant wireless network that can provide high data rates in a limited coverage area. While emerging mobile WiMAX (IEEE802.16e) can provide a wireless broadband access to mobile users in a wide coverage area. These two different technolgies will co-exist while complementing each other in some regions, hence, a mobile node (MN) with dual interfaces traverses and executes many handovers (HOs) between 802.11g and 802.16e. Meanwhile, there is a huge demand for Voice over IP (VoIP) service over wireless networks. However, VoIP is a delay and loss sensitive application, hence, VoIP session is more likely to be deteriorated during HO between 802.11g and 802.16e. In order to maintain quality of VoIP session during HO, we proposed Vertical Handover Management (VHM) for VoIP session that focuses on HO initiation and decision strategy according to the wireless link condition and congestion state of wireless networks. The VHM exploits request to send (RTS) retries and round trip time (RTT) between an MN and an access point in an 802.11g interface as well as a carrier to interference noise ration (CINR) level and MN’s queue length of an 802.16e interface as HO triggers. We then conducted simulation experiments to evaluate the effectiveness of our proposed VHM using QualNet 4.5. Our simulation results show that our proposed VHM can preserve the quality of VoIP session during such HOs.
