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121.
Angelika Hartung Anna-Maria Ordelheide Harald Staiger Martina Melzer Hans-Ulrich Häring Reiner Lammers 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2013,1833(12):2803-2811
Akt kinases are important mediators of the insulin signal, and some Akt substrates are directly involved in glucose homeostasis. Recently, Girdin has been described as an Akt substrate that is expressed ubiquitously in mammals. Cells overexpressing Girdin show an enhanced Akt activity. However, not much is known about Girdin's role in insulin signaling. We therefore analyzed the role of Girdin in primary human myotubes and found a correlation between Girdin expression and insulin sensitivity of the muscle biopsy donors, as measured by a hyperinsulinemic–euglycemic clamp. To understand this finding on a cellular level, we then investigated the function of Girdin in C2C12 mouse myoblasts. Girdin knock-down reduced Akt and insulin receptor substrate-1 phosphorylation. In contrast, stable overexpression of Girdin in C2C12 cells strikingly increased insulin sensitivity through a massive upregulation of the insulin receptor and enhanced tyrosine phosphorylation of insulin receptor substrate-1. Furthermore, Akt and c-Abl kinases were constitutively activated. To investigate medium-term insulin responses we measured glucose incorporation into glycogen. The Girdin overexpressing cells showed a high basal glycogen synthesis that peaked already at 1 nM insulin. Taken together, we characterized Girdin as a new and major regulator of the insulin signal in myoblasts and skeletal muscle. 相似文献
122.
Sabine Frank Martin Heni Anja Moss Julia von Schnurbein Sadaf Farooqi Hans-Ulrich H?ring Andreas Fritsche Hubert Preissl Martin Wabitsch 《PloS one》2013,8(6)
Context
Congenital leptin deficiency, caused by a very rare mutation in the gene encoding leptin, leads to severe obesity, hyperphagia and impaired satiety. The only systemic treatment is the substitution with metreleptin leading to weight reduction based on hormonal changes. Several studies have also shown alterations in brain function after metreleptin therapy. In a previous study, we were able to show changes in homeostatic (hypothalamus) and reward-related brain areas (striatum, orbitofrontal cortex (OFC), substantia nigra/ventral tegmental area, amygdala) 3 days and 6 months after therapy start in a leptin-deficient adolescent girl. To further access the time course of functional brain activation changes, we followed the patient for 2 years after initiation of the therapy.Design, Patient
Functional magnetic resonance imaging during visual stimulation with food (high- and low-caloric) and non-food pictures was performed 1 and 2 years after therapy start in the previously described patient.Results
The comparison of ‘food vs. non-food’ pictures showed a stabilization of the long-term effects in the amygdala and in the OFC. Therefore, no significant differences were observed between 6 months compared to 12 and 24 months in these regions. Additionally, a reduction of the frontopolar cortex activity over the whole time span was observed. For the comparison of high- and low-caloric pictures, long-term effects in the hypothalamus showed an assimilating pattern for the response to the food categories whereas only acute effects after 3 months were observed in hedonic brain regions.Conclusion
This follow-up study shows that the long lasting benefit of metreleptin therapy is also associated with activation changes in homeostatic, hedonic and frontal control regions in congenital leptin deficiency. 相似文献123.
124.
Koselj K Schnitzler HU Siemers BM 《Proceedings. Biological sciences / The Royal Society》2011,278(1721):3034-3041
Foragers base their prey-selection decisions on the information acquired by the sensory systems. In bats that use echolocation to find prey in darkness, it is not clear whether the specialized diet, as sometimes found by faecal analysis, is a result of active decision-making or rather of biased sensory information. Here, we tested whether greater horseshoe bats decide economically when to attack a particular prey item and when not. This species is known to recognize different insects based on their wing-beat pattern imprinted in the echoes. We built a simulation of the natural foraging process in the laboratory, where the bats scanned for prey from a perch and, upon reaching the decision to attack, intercepted the prey in flight. To fully control echo information available to the bats and assure its unambiguity, we implemented computer-controlled propellers that produced echoes resembling those from natural insects of differing profitability. The bats monitored prey arrivals to sample the supply of prey categories in the environment and to inform foraging decisions. The bats adjusted selectivity for the more profitable prey to its inter-arrival intervals as predicted by foraging theory (an economic strategy known to benefit fitness). Moreover, unlike in previously studied vertebrates, foraging performance of horseshoe bats was not limited by costly rejections of the profitable prey. This calls for further research into the evolutionary selection pressures that sharpened the species's decision-making capacity. 相似文献
125.
126.
Alfred Opolka Sabine Ratzinger Thomas Schubert Hans-Ulrich Spiegel Joachim Grifka Peter Bruckner Axel Probst Susanne Gr?ssel 《Matrix biology》2007,26(2):85-95
Fracture repair recapitulates in adult organisms the sequence of cell biological events of endochondral ossification during skeletal development and growth. After initial inflammation and deposition of granulation tissue, a cartilaginous callus is formed which, subsequently, is remodeled into bone. In part, bone formation is influenced also by the properties of the extracellular matrix of the cartilaginous callus. Deletion of individual macromolecular components can alter extracellular matrix suprastructures, and hence stability and organization of mesenchymal tissues. Here, we took advantage of the collagen IX knockout mouse model to better understand the role of this collagen for organization, differentiation and maturation of a cartilaginous template during formation of new bone. Although a seemingly crucial component of cartilage fibrils is missing, collagen IX-deficient mice develop normally, but are predisposed to premature joint cartilage degeneration. However, we show here that lack of collagen IX alters the time course of callus differentiation during bone fracture healing. The maturation of cartilage matrix was delayed in collagen IX-deficient mice calli as judged by collagen X expression during the repair phase and the total amount of cartilage matrix was reduced. Entering the remodeling phase of fracture healing, Col9a1(-/-) calli retained a larger percentage of cartilage matrix than in wild type indicating also a delayed formation of new bone. We concluded that endochondral bone formation can occur in collagen IX knockout mice but is impaired under conditions of stress, such as the repair of an unfixed fractured long bone. 相似文献
127.
128.
Distinct domains of yeast cortical tag proteins Bud8p and Bud9p confer polar localization and functionality
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In Saccharomyces cerevisiae, diploid yeast cells follow a bipolar budding program, which depends on the two transmembrane glycoproteins Bud8p and Bud9p that potentially act as cortical tags to mark the cell poles. Here, we have performed systematic structure-function analyses of Bud8p and Bud9p to identify functional domains. We find that polar transport of Bud8p and Bud9p does not depend on N-terminal sequences but instead on sequences in the median part of the proteins and on the C-terminal parts that contain the transmembrane domains. We show that the guanosine diphosphate (GDP)/guanosine triphosphate (GTP) exchange factor Bud5p, which is essential for bud site selection and physically interacts with Bud8p, also interacts with Bud9p. Regions of Bud8p and Bud9p predicted to reside in the extracellular space are likely to confer interaction with the N-terminal region of Bud5p, implicating indirect interactions between the cortical tags and the GDP/GTP exchange factor. Finally, we have identified regions of Bud8p and Bud9p that are required for interaction with the cortical tag protein Rax1p. In summary, our study suggests that Bud8p and Bud9p carry distinct domains for delivery of the proteins to the cell poles, for interaction with the general budding machinery and for association with other cortical tag proteins. 相似文献
129.
Anja B?hm Anna Halama Tobias Meile Marty Zdichavsky Rainer Lehmann Cora Weigert Andreas Fritsche Norbert Stefan Alfred K?nigsrainer Hans-Ulrich H?ring Martin Hrabě de Angelis Jerzy Adamski Harald Staiger 《PloS one》2014,9(4)