Physiology And Molecular Biology Of Intestinal Glucose Transport Biology Essay
Glucose is an of import beginning of foods for mammals. It non merely provides energy but besides serves as a substrate for big molecules such as glycoproteins, proteoglycans, glycolipids and nucleic acids. Hence it plays a major function in keeping cellular homeostasis and cellular metamorphosis ( Shirazi-Beechey, 1995 ) .
The consumption of glucose by cells is accomplished with the aid of bearer proteins present in the plasma membrane. They bind with glucose and so transport it across the lipid bilayer. Two types of bearer proteins have been identified in mammalian cells ;
the Na+-coupled glucose cotransporters ( SGLT )
the facilitative glucose transporter ( GLUT )
The map of these transporters is to transport monosaccharoses viz. glucose, galactose and fructose from the lms of bowel to the blood ( Ferraris, 2001 ) .
The merchandises of saccharide digestion, D_glucose and D-galactose are transported from the lms across the coppice boundary line into the cells by SGLT1 and roll up at that place. These merchandises are so passed from these cells into the systemic circulation via GLUT 2 down the concentration gradient ( Shirazi-Beechey, 1995 ) .
The survey of conveyance measurings and ligand-binding experiments suggest that there are more than one type of SGLT proteins nevertheless so far merely one type has been found ; the SGLT1 ( Ferraris, 2001 ) .
SGLT1 is present in the coppice boundary line or apical membrane of the enteric epithelial cells and is responsible for conveyance of glucose and galactose along with Na+ ions into the cytosol from lms of the bowel. This motion occurs against the concentration gradient and electrochemical gradient. This gradient is maintained by virtuousness of an active conveyance of Na+ out of the cell at basolateral membrane which is done by Na+/K+ active conveyance ( Shirazi-Beechey, 1995 ) .
This transporter favours hexose sugars with equatorial hydroxyl at place C2. Hence a figure of natural dietetic saccharides such as D-glucose and D-galactose and nonmetabolized
sugars, 3-O-methyl-a, ~-glucopyranosidaen vitamin D methyl-a, D-glucopyranoside can be transported. Bing a cotransporter it needs matching which is merely done with Na+ ions and other ions such as K+ and Li+ do non transport out this conveyance ( Shirazi-Beechey, 1995 ) .
The SGLT1 consists of 664 aminic acids in worlds. The secondary construction reveals that it spans the plasma membrane 12 times.
The Effect of Diet
It has been identified that dietetic saccharides can change the degrees of enteric coppice boundary line membrane Na+/glucose cotransporter. Progresss in the molecular biological science techniques have led to an addition in the apprehension of the molecular mechanisms which regulate the conveyance of sugars via SGLT1.
Initial grounds came from carnal surveies and it was shown that when there is an addition in the saccharide content of diets given to rats and mice, the rate of conveyance of D-glucose across the intestinal wall besides increased 2-3 old and was reversible. On farther geographic expedition, it was shown that when mice devouring a saccharide free diet were later switched to a high saccharide diet, Na+-dependent D-glucose about doubled in 24 hours. Similarly, when mice on a high saccharide diet were switched to a saccharide free diet, it took 1-3 yearss before brush boundary line glucose consumption decreased significantly from control values ( Shirazi-Beechey, 1995 ) . An extract of glucose in the sheep enteric lms that does non usually show SGLT or messenger RNA showed a pronounced addition in SGLT1 activity and copiousness. However, messenger RNA was non increased hence proposing that the dietetic ordinance of SGLT1 look is likely modulated by some translational or posttranslational mechanism ( Ferraris, 2001 ) .
In worlds besides, SGLT1 may be affected by diet ( Dyer, 1997 ) . It has been shown by assorted surveies that the glucose conveyance was greater in the coppice boundary line membrane cysts of normal enteric tissues in contrast to the cysts obtained from the bordering dysfunctional tissue with reduced exposure to enteric foods. This reduced transportation of glucose was a consequence of reduced look of SGLT1 and was independent of morphology of the villus.
Changes in the degree of Na+ besides have an consequence on the glucose conveyance in enteric cells as was shown by the surveies showing that a reduced Na consumption in the diet reduces the enteric conveyance of glucose making a upper limit within 2 yearss ( Garriga et al, 2000 ) . However, a higher dietetic Na+ was shown to hold no consequence.
The Crypt-illus Axis
Enterocytes along the crypt-villus axis respond otherwise due to fluctuations in the province of distinction along the crypt villus axis. Expression of SGLT1 protein and SGLT1 messenger RNA along the crypt villus-axis has been studied utilizing immunocytochemical and in situ hybridisation techniques. Consequences indicated that SGLT1 protein was expressed along the full length of villus but the oncoming of glucose conveyance occured near the crypt-villus junction ( ( Shirazi-Beechey, 1995 ) .
Hence, in SGLT1 theoretical account, the activity in villus cells can non be controlled by diet ( Figure1 ) ; the clip class of alteration as shown in the figure 1 is due to migration and distinction of cells
Figure:1 A theoretical account of SGLT1 ordinance by diet ( Beginning: Ferraris, 2001 )
These facilitated glucose transporters are found in all mammalian cells. Different isoforms of GLUT are from GLUT1 to Gorge 7.
GLUT 1 -4 have a decently categorised tissue distribution and they have a function in the motion of glucose across the plasma membrane in and out of the cells along its chemical gradient ( Kellett et al, 2008 ) . GLUT 5 has been recognized as a fructose transporter and has a omnipresent presence while GLUT6 is a pesudogene and hence is without a merchandise. GLUT7 has been reported to hold a function in conveyance of glucose in endoplasmic Reticulum of enterocytes.
GLUT2 has been discussed here owing to its primary function in glucose conveyance.
It has been widely accepted that GLUT2 is involved in the basolateral conveyance of sugar ( Kellett et al, 200o ) . It has been proposed that GLUT5 controls the traffic at the brush-border membrane while GLUT2 controls the traffic at the basolateral membrane of the rat bowel ( Ferraris, 2001 ) .
A recent survey suggested that GLUT2 is besides present at the coppice boundary line of normal cells in rat bowel and plays a function in glucose and fructose conveyance. However, it has non been possible to corroborate its presence in vitro as GLUT2 is assumed to be quickly lost from the coppice boundary line membrane shortly after remotion of jejunum from the animate being ( Ferraris, 2001 ) . A survey by Kellet et Al ( 2008 ) suggested that apical GLUT2 might be present which play an of import function in enteric soaking up of glucose and fruit sugar. They have besides suggested that this enlisting of GLUT2 to apical surface or coppice boundary line is in response to dietary glucose and contributes towards the diffuse constituent of enteric glucose soaking up. This GLUT2 has hence become a possible mark for agents that can be used for therapy of diabetes and fleshiness ( Kwon et al, 2007 ) .
One of such surveies attempted to prove whether the major sugar transporters such as SGLT1, GLUT2 and GLUT5 can be inhibited by the enteric luminal contents of course present in nutrient such as flavonoids which were tested in this survey ( Kwon et al, 2007 ) . The consequences indicated that an effectual suppression of glucose and fructose conveyance by GLUT2 was done by normally consumed flavonoids such as flavonols, myricetin and fisetin. This was a non-competitive suppression. However, no such consequence was observed in instance of other important sugar transporters which are SGLT1 and GLUT5. & A ; Acirc ; Therefore these flavonoids can play a critical function in get bying with jobs such as fleshiness and diabetes.
In an attempt to look into the diurnal form of activity among the hexose transporters, a survey was carried out on rats as they have nocturnal eating wonts ( Corpe and Burant, 1996 ) . The degrees of messenger RNA and proteins were determined for three major transporters i.e. SGLT1, GLUT2 and GLUT5. It was shown that the degrees of GLUT-5, GLUT-2, and SGLT-1 mRNA vary in a diurnal manner, with increased messenger RNA for each of these transporters and occurred before the oncoming of extremum feeding although the exact mechanisms behind this fluctuation remain to be elucidated. GLUT5 protein besides increased although out of stage in comparing to GLUT5 mRNA nevertheless no diurnal fluctuation was observed in GLUT5 protein. A fructose rich diet was accompanied by lift in degrees of GLUT5 messenger RNA and protein whereas there was important consequence on diurnal form of GLUT2 and SGLT messenger RNA.
It is apparent from the above treatment that the enteric conveyance of glucose is mediated by two major glucose transporters viz. SGLT1 and GLUT2. SGLT1 is chiefly responsible for conveyance of glucose from the lms into the cytosol through the coppice boundary line via a Na+ coupled conveyance mechanism. GLUT2 maps to transport this glucose into the systemic circulation at the basolateral cellular boundary line through facilitated diffusion. However, recent grounds identified the presence of an apical GLUT2 which is thought to be recruited in response to dietetic glucose. These transporters are thought to hold changing looks in response to altering glucose form in diet. A glucose rich diet increases the SGLT1 proteins in enterocytes and hence increased conveyance of glucose. A low salt ( Na+ ) diet decreases the enteric conveyance of glucose. Similarly, more dietetic glucose increases the look of GLUT2. Food substances like falvonoids inhibit the GLUT2 associated conveyance of glucose and hence are possible curative agents in fleshiness intervention. Furthermore, SGLT1, GLUT2 and GLUT5 messenger RNAs have been shown to exhibit a diurnal fluctuation in rats.