Effect of photobiomodulation therapy on the regulation of glucose uptake by lymphocytes in diabetes mellitus (Review)

For most cells, including lymphocytes, glucose is a primary energy source, and, therefore, it is vital to understand the regulatory mechanisms that control the work of glucose transporters. Lymphocytes are pivotal for mediation of immune and inflammatory responses. A feature of lymphocytes is increasing glucose utilization during activation of the immune function, which is strongly dependent on glucose uptake. Some studies show that elevated glucose concentration in diabetes mellitus affects lymphocytes’ glucose transporters expression, whichcorrelates with impaired immune functions and may become one of the predisposing factors of contracting infectious diseases. Recent studies have focused on glucose transporters as therapeutic targets for a variety of diseases, including diabetes mellitus. This review demonstrates the effect of photobiomodulationtherapy on glucose uptake by Na+-coupled glucose carrier SGLT1 and facilitated diffusion glucose carriers of the GLUT family (GLUT1, GLUT3, GLUT4) in normal and diabetic lymphocytes.

Expression of JAK3 Sensitive Na+ Coupled Glucose Carrier SGLT1 in Activated Cytotoxic T Lymphocytes

Background: Similar to tumor cells, activated T-lymphocytes generate ATP mainly by glycolytic degradation of glucose. Lymphocyte glucose uptake involves non-concentrative glucose carriers of the GLUT family. In contrast to GLUT isoforms, Na+-coupled glucose-carrier SGLT1 accumulates glucose against glucose gradients and is effective at low extracellular glucose concentrations. The present study explored expression and regulation of SGLT1 in activated murine splenic cytotoxic T cells (CTLs) and human Jurkat T cells. Methods: FACS analysis, immunofluorescence, confocal microscopy, chemiluminescence and Western blotting were employed to estimate SGLT1 expression, function and regulation in lymphocytes, as well as dual electrode voltage clamp in SGLT1 ± JAK3 expressing Xenopus oocytes to quantify the effect of janus kinase3 (JAK3) on SGLT1 function. Results: SGLT1 is expressed in murine CTLs and also in human Jurkat T cells. 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake was significantly decreased by SGLT1-blocker phloridzin (0.2 mM) and by pharmacological inhibition of JAK3 with WHI-P131 (156 µM), WHI-P154 (11.2 µM) and JAK3 inhibitor VI (0.5 µM). Electrogenic glucose transport (Iglucose) in Xenopus oocytes expressing human SGLT1 was increased by additional expression of human wild type JAK3, active A568VJAK3 but not inactive K851AJAK3. Coexpression of JAK3 enhanced the maximal transport rate without significantly modifying affinity of the carrier. Iglucose in SGLT1+JAK3 expressing oocytes was significantly decreased by WHI-P154 (11.2 µM). JAK3 increased the SGLT1 protein abundance in the cell membrane. Inhibition of carrier insertion by brefeldin A (5 µM) in SGLT1+JAK3 expressing oocytes resulted in a decline of Iglucose, which was similar in presence and absence of JAK3. Conclusions: SGLT1 is expressed in murine cytotoxic T cells and human Jurkat T cells and significantly contributes to glucose uptake in those cells post activation. JAK3 up-regulates SGLT1 activity by increasing the carrier protein abundance in the cell membrane, an effect enforcing cellular glucose uptake into activated lymphocytes and thus contributing to the immune response.

Carbohydrate metabolism and metabolic disorders in horses

Horses evolved consuming primarily fermentable forage carbohydrates, but forage diets have been traditionally supplemented with grain meals rich in starch and sugar in order to provide additional calories, protein and micronutrients. Starch and sugar are important for performance horses, but the consumption starch-rich meals may cause equine digestive and metabolic disorders. The critical capacity for preileal starch digestibility appears to be 0.35 to 0.4% but may be as little, depending on the source of starch. Small intestinal absorption of simple sugars is limited by the activity and expression of two classes of glucose carrier proteins, which are affected by chronic intake of hydrolyzable carbohydrate but may be sluggish to respond to abrupt changes in diet, further exacerbating the risk of overload. The most rapid fermentation occurs during starch overload or in the presence of fructans. Rapid fermentation perturbs the microbial and pH balance of the cecum and colon, favoring proliferation of Lactobacillus spp and acid production and increasing the risk of colic and laminitis. In addition to digestive disturbances, feeding grain concentrates rich in hydrolyzable carbohydrate may increase the risk of insulin resistance, which has been associated with obesity, laminitis and chronic founder, developmental orthopedic disease, and Cushing's disease in horses. This threshold concentration of starch intake may be a starting point for horse owners, feed manufacturers and veterinarians that may be claimed to be "low" enough to reduce risk in insulin resistant horses sensitive to grain-associated disorders.