Faculty Opinions recommendation of Metabolic changes in glucose transporter-deficient Leishmania mexicana and parasite virulence.

Author(s):  
Roberto Docampo
Author(s):  
Stefania Camastra ◽  
Maria Palumbo ◽  
Ferruccio Santini

AbstractBariatric surgery determines a rearrangement of the gastrointestinal tract that influences nutrient handling and plays a role in the metabolic changes observed after surgery. Most of the changes depend on the accelerated gastric emptying observed in Roux-en-Y gastric bypass (RYGB) and, to a lesser extent, in sleeve gastrectomy (SG). The rapid delivery of meal into the jejunum, particularly after RYGB, contributes to the prompt appearance of glucose in peripheral circulation. Glucose increase is the principal determinant of GLP-1 increase with the consequent stimulation of insulin secretion, the latter balanced by a paradoxical glucagon increase that stimulates EGP to prevent hypoglycaemia. Protein digestion and amino acid absorption appear accelerated after RYGB but not after SG. After RYGB, the adaptation of the gut to the new condition participates to the metabolic change. The intestinal transit is delayed, the gut microbioma is changed, the epithelium becomes hypertrophic and increases the expression of glucose transporter and of the number of cell secreting hormones. These changes are not observed after SG. After RYGB—less after SG—bile acids (BA) increase, influencing glucose metabolism probably modulating FXR and TGR5 with an effect on insulin sensitivity. Muscle, hepatic and adipose tissue insulin sensitivity improve, and the gut reinforces the recovery of IS by enhancing glucose uptake and through the effect of the BA. The intestinal changes observed after RYGB result in a light malabsorption of lipid but not of carbohydrate and protein. In conclusion, functional and morphological adaptations of the gut after RYGB and SG activate inter-organs cross-talk that modulates the metabolic changes observed after surgery.Level of evidence Level V, narrative literature review.


2020 ◽  
Author(s):  
Felice D. Kelly ◽  
Khoa D. Tran ◽  
Jess Hatfield ◽  
Kat Schmidt ◽  
Marco A. Sanchez ◽  
...  

AbstractPrevious studies in Leishmania mexicana have identified the cytoskeletal protein KHARON as being important for both flagellar trafficking of the glucose transporter GT1 and for successful cytokinesis and survival of infectious amastigote forms inside mammalian macrophages. KHARON is located in three distinct regions of the cytoskeleton: the base of the flagellum, the subpellicular microtubules, and the mitotic spindle. To deconvolve the different functions for KHARON, we have identified two partner proteins, KHAP1 and KHAP2, that associate with KHARON. KHAP1 is located only in the subpellicular microtubules, while KHAP2 is located at the subpellicular microtubules and the base of the flagellum. Both the KHAP1 and KHAP2 null mutants are unable to execute cytokinesis but are able to traffic GT1 to the flagellum. These results confirm that KHARON assembles into distinct functional complexes and that the subpellicular complex is essential for cytokinesis and viability of disease-causing amastigotes but not for flagellar membrane trafficking.


2014 ◽  
Vol 29 (1) ◽  
pp. 11-24 ◽  
Author(s):  
Dayana Rodriguez‐Contreras ◽  
Hamide Aslan ◽  
Xiuhong Feng ◽  
Khoa Tran ◽  
Phillip A. Yates ◽  
...  

2003 ◽  
Vol 100 (7) ◽  
pp. 3901-3906 ◽  
Author(s):  
R. J. S. Burchmore ◽  
D. Rodriguez-Contreras ◽  
K. McBride ◽  
M. P. Barrett ◽  
G. Modi ◽  
...  

2007 ◽  
Vol 153 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Dayana Rodriguez-Contreras ◽  
Xiuhong Feng ◽  
Kristie M. Keeney ◽  
H.G. Archie Bouwer ◽  
Scott M. Landfear

2011 ◽  
Vol 175 (1) ◽  
pp. 39-48 ◽  
Author(s):  
Xiuhong Feng ◽  
Torben Feistel ◽  
Cosmo Buffalo ◽  
Ashley McCormack ◽  
Elizabeth Kruvand ◽  
...  

2006 ◽  
Vol 281 (29) ◽  
pp. 20068-20076 ◽  
Author(s):  
Dayana Rodríguez-Contreras ◽  
Scott M. Landfear

2020 ◽  
Vol 295 (37) ◽  
pp. 13106-13122 ◽  
Author(s):  
Felice D. Kelly ◽  
Khoa D. Tran ◽  
Jess Hatfield ◽  
Kat Schmidt ◽  
Marco A. Sanchez ◽  
...  

Previous studies in Leishmania mexicana have identified the cytoskeletal protein KHARON as being important for both flagellar trafficking of the glucose transporter GT1 and for successful cytokinesis and survival of infectious amastigote forms inside mammalian macrophages. KHARON is located in three distinct regions of the cytoskeleton: the base of the flagellum, the subpellicular microtubules, and the mitotic spindle. To deconvolve the different functions for KHARON, we have identified two partner proteins, KHAP1 and KHAP2, which associate with KHARON. KHAP1 is located only in the subpellicular microtubules, whereas KHAP2 is located at the subpellicular microtubules and the base of the flagellum. Both KHAP1 and KHAP2 null mutants are unable to execute cytokinesis but are able to traffic GT1 to the flagellum. These results confirm that KHARON assembles into distinct functional complexes and that the subpellicular complex is essential for cytokinesis and viability of disease-causing amastigotes but not for flagellar membrane trafficking.


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