Hindbrain Astrocyte Glucodetectors and Counterregulation
Ruth B.S. Harris in Appetite and Food Intake, 2017
Rapid signaling of glucose status in intact hindbrain astrocytes may involve the action of a GLUT2-glucose “transceptor” (that may not be present in hippocampal or cultured astrocytes). GLUT2 is the only mammalian glucose transporter that may act as a “transceptor,” i.e., a protein that functions as both a transporter and receptor (Figure 10.6). A GLUT2-based transceptor could detect changes in extracellular glucose concentration and then rapidly initiate a calcium-based transduction event. This system would function somewhat like a ligand-gated cation channel or a membrane G-protein-based receptor linked to ER calcium release. Transgenic mice generated to knock down a GLUT2-intracellular loop domain yielded animals that demonstrated an inability to detect glucose but left the GLUT2-dependent glucose transport unaffected (Stolarczyk et al. 2010, 2007). While the possibility of the GLUT2 “transceptor” is intriguing, any mechanism connecting GLUT2 transceptor-like activation with downstream changes in calcium remains uninvestigated.
Carbohydrate and glycosylation disorders
Steve Hannigan in Inherited Metabolic Diseases: A Guide to 100 Conditions, 2018
Symptoms of this disorder present in infancy and include failure to grow or gain weight (failure to thrive), enlargement of the liver (hepatomegaly) and failure of the bones to harden due to a deiciency of phosphate (hypophosphataemic rickets). Other symptoms include a protruding abdomen, enlarged kidneys, growth defects and decreased bone calciication, decreased bone density or reduced bone mass (osteo-penia). Long periods of time without food may cause mild low blood sugar and raised levels of ketone bodies in the body tissues. Findings include the presence of high levels of lipids in the blood (hyperlipidaemia), massive excretion of glucose in the urine (glucosuria), high levels of protein in the urine (proteinuria) and abnormal urinary excretion of phosphate (hyperphosphaturia) and bicarbonate (renal tubular acidosis or RTA). Other indings include the presence of amino acids in the urine (aminoa-ciduria) and usually a high level of organic acids, lactate, ketone bodies and carnitine in the urine. The GLUT2 gene may be expressed in the liver, kidneys, pancreas and intestines.
Genetics of Endocrine Disorders and Diabetes Mellitus
George H. Gass, Harold M. Kaplan in Handbook of Endocrinology, 2020
There is some evidence for a minor role of Glut2 in the etiology of diabetes. A missense mutation (Val197 to Ile) that destroys the transport activity of Glut291 has been identified in 1 of 48 patients with gestational diabetes.92 Studies have shown a possible association between a restriction length polymorphism of Glut2 and NIDDM in a British and a Caucasian population.88,93 But, polymorphism analyses in NIDDM patients from populations of Pima Indians,94 African Americans,90 British Caucasians,95 and MODY patients from French,96 Danish,97 and British97 families show no association of the Glut2 gene with diabetes. Based on all the available data, it appears that Glut2 has a minor role, if any, in the susceptibility to NIDDM or MODY
Cross talk between exosomes and pancreatic β-cells in diabetes
Published in Archives of Physiology and Biochemistry, 2022
One of the major developments in lncRNAs over the past several years is that lncRNAs exist in various body fluids, such as serum (Shen et al.2017), plasma (Tan et al.2016), and urine (Terracciano et al.2017). Circulating lncRNAs could target distant cells or organs and perform a regulatory function in a new location through exosomes. β-cell-derived lncRNAs in the circulation can restore insulin synthesis and increase the number of pancreatic β-cells. PDX-1 and MafA are key proteins for insulin secretion regulation (Guo et al.2012). GLUT2 is a glucose transporter essential for activating glucose-sensitive genes (Thorens 2015). Microarray technology indicated that the circulating level of lncRNA-p3134 in T2D patients was higher than in non-diabetic controls. Further research in MIN6 cells and isolated mouse islet cells shows β cell-derived lncRNA-p3134 regulating the expression of PDX-1, MafA, and transcription factor 7-like 2, thereby enhancing GSIS (Figure 3⑤). Furthermore, when the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signals were blocked by specific inhibitor, lncRNA-p3134-mediated insulin secretion decreased (Ruan et al.2018) (Figure 3⑤). Simulation of the PI3K/AKT pathway phosphorylates the mammalian target of rapamycin (mTOR), governing promoting cell proliferation (Ruan et al.2018). In summary, circulating lncRNA-p3134 maintains insulin levels through regulating both insulin section and β-cell mass.
Association between the membrane transporter proteins and type 2 diabetes mellitus
Published in Expert Review of Clinical Pharmacology, 2020
GLUT2 is the chief mediator of glucose sensing and homeostasis. GLUT2 present in the intestinal cells is responsible for the initial glucose uptake in the organisms. Reports show that GLUT2 mediates the intestinal glucose transport and it is regulated within jejunal and ileal membranes [34,35]. Followed by the intestinal glucose absorption, activation of the glucose-sensing cells of the hepato-portal vein results in the stimulation of insulin secretion since these cells contain GLUT2 and many physiological responses. The renal reabsorption of glucose is carried out in two sequential steps. Initially, the influx of glucose is mediated by sodium/glucose cotransporter (SGLT2) which increases the intracellular glucose concentration. Thereafter, glucose efflux from the renal tubules into interstitial space is achieved by GLUT2 located exclusively in the basolateral membranes [36].
Antioxidant and Anti-Diabetic Functions of a Polyphenol-Rich Sugarcane Extract
Published in Journal of the American College of Nutrition, 2019
Jin Ji, Xin Yang, Matthew Flavel, Zenaida P.-I. Shields, Barry Kitchen
To study the effect of the PRSE on glucose and fructose transporter GLUT2/GLUT5, Caco-2 human intestinal cells were maintained in the same manner as described above, and monolayers of Caco-2 cells (100% confluence) obtained 9 days after the initial seeding are used. Caco-2 cell monolayers were first treated with six concentrations of PRSE or quercetin for 24 hours. Total RNA was then extracted from the treated Caco-2 cells using the MagMAX™-96 Total RNA Isolation Kit (Thermo Fisher Scientific) according to manufacturer’s instruction. cDNA was synthesized from total RNA by using High Capacity RNA-to-cDNA Kits (Thermo Fisher Scientific) and a Veriti thermal cycler (Thermo Fisher Scientific). Real-time quantitative Polymerase chain reaction (PCR) was performed in an Applied Biosystems Real-Time Quantitative PCR system (Thermo Fisher Scientific) as described previously (13). Specifically, the primer pair used for GLUT2 was 5′-CAG GAC TAT ATT GTG GGC TAA-3′ (forward) and 5′-CTG ATG AAA AGT GCC AAG T-30 (reverse) and for GLUT5 was 5′-ACC GTG TCC ATG TTT CCA TT-3′ (forward) and 5′-ATT AAG ATC GCA GGC ACG AT-3′ (reverse). Human beta-actin was used as the housekeeping genes. Expression of GLUT2 and GLUT5 mRNA in Caco-2 cells that were treated with six different concentrations of PRSE or quercetin was determined by real-time quantitative PCR and compared with those of Caco-2 cells treated with vehicle.