Glucose uptake
Method of glucose uptake differs throughout tissues depending on two factors; the metabolic needs of the tissue and availability of glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

. The two ways in which glucose uptake can take place are facilitated diffusion (a passive process) and secondary active transport (an active process which indirectly requires the hydrolysis of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...


Facilitated diffusion

There are over 10 different types of glucose transporter; however, the most significant for study are GLUT1-4.

Glucose transporter 1 , also known as solute carrier family 2, facilitated glucose transporter member 1 is a protein that in humans is encoded by the SLC2A1 gene...

 and GLUT3
Glucose transporter 3 , also known as solute carrier family 2, facilitated glucose transporter member 3 is a protein that in humans is encoded by the SLC2A3 gene. GLUT3 facilitates the transport of glucose across the plasma membranes of mammalian cells...

 are located in the plasma membrane of cells throughout the body, as they are responsible for maintaining a basal rate of glucose uptake. Basal blood glucose level is approximately 5mM. The Km value (an indicator of the affinity of the transporter protein for glucose molecules; a low Km value suggests a high affinity)of the GLUT1 and GLUT3 proteins is 1mM; therefore GLUT1 and GLUT3 have a high affinity for glucose and uptake from the bloodstream is constant.

Glucose transporter 2 also known as solute carrier family 2 , member 2 is a transmembrane carrier protein that enables passive glucose movement across cell membranes. It is the principal transporter for transfer of glucose between liver and blood, and for renal glucose reabsorption...

 in contrast has a high Km value (15-20mM) and therefore a low affinity for glucose. They are located in the plasma membranes of hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...

s and pancreatic
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...

 beta cell
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...

s, and their high Km allows for glucose sensing; rate of glucose entry is proportional to blood glucose levels.

Glucose transporter type 4, also known as GLUT4, is a protein that in humans is encoded by the GLUT4 gene. GLUT4 is the insulin-regulated glucose transporter found in adipose tissues and striated muscle that is responsible for insulin-regulated glucose translocation into the cell...

 transporters are insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

 sensitive, and are found in muscle and adipose tissue. As muscle is a principle storage site for glucose and adipose tissue for triglyceride
A triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....

 (into which glucose can be converted for storage), GLUT4 is important in post-prandial uptake of excess glucose from the bloodstream. The drug Metformin
Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...

 phosphorylates GLUT4, thereby increasing its sensitivity to insulin.

During fasting, some GLUT4 transporters will be expressed at the surface of the cell. However, most will be found within the plasma membranes of cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

ic vesicles
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...

 within the cell. After a meal and at the binding of insulin (released from the islets of Langerhans
Islets of Langerhans
The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas...

) to receptors on the cell surface, a signalling cascade begins which culminates in the movement of the cytoplasmic vesicles toward the cell surface membrane. Upon reaching the plasmalemma, the vesicles fuse with the membrane, increasing the number of GLUT4 transporters expressed at the cell surface, and hence increasing glucose uptake.

Secondary active transport

Facilitated diffusion can occur between the bloodstream and cells as the concentration gradient between the extracellular and intracellular environments is such that no ATP hydrolysis is required.

However in the kidney, glucose is reabsorbed from the filtrate in the tubule lumen, where it is at a relatively low concentration, passes through the columnar epithelia
Columnar epithelia
Columnar epithelia are epithelial cells whose heights are at least four times their width. Columnar epithelia are divided into simple , and stratified .* Simple columnar epithelia* Stratified columnar epithelia...

 lining the kidney tubule, and into the bloodstream where glucose is at a comparatively high concentration. Therefore the concentration gradient of glucose opposes its reabsorption, and energy is required for its transport.

The secondary active transport of glucose in the kidney is Na+
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 linked; therefore an Na+ gradient must be established. This is achieved through the action of the Na+/K+ pump, the energy for which is provided through the hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

 of ATP. Three Na+ ions are extruded from the cell in exchange for two K+ ions entering through the intramembrane enzyme Na+/K+-ATPase
Na+/K+-ATPase is an enzyme located in the plasma membrane in all animals.- Sodium-potassium pumps :Active transport is responsible for cells containing relatively high...

; this leaves a relative deficiency of Na+ in the intracellular compartment. Na+ ions diffuse down their concentration gradient into the columnar epithelia, co-transporting
Co-transport, also known as coupled transport or secondary active transport, refers to the simultaneous or sequential passive transfer of molecules or ions across biological membranes in a fixed ratio...

 glucose. Once inside the epithelial cells, glucose reenters the bloodstream through facilitated diffusion through GLUT2 transporters.

Hence reabsorption of glucose is dependent upon the existing sodium gradient which is generated through the active functioning of the NaKATPase. As the cotransport
Co-transport, also known as coupled transport or secondary active transport, refers to the simultaneous or sequential passive transfer of molecules or ions across biological membranes in a fixed ratio...

 of glucose with sodium from the lumen does not directly require ATP hydrolysis but depends upon the action of the ATPase, this is described as secondary active transport.

There are two types of secondary active transporter found within the kidney tubule; close to the glomerulus
A glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...

, where glucose levels are high, SGLT2 has a low affinity yet high capacity for glucose transport. Close to the loop of Henle
Loop of Henle
In the kidney, the loop of Henle is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after its discoverer F. G. J...

 and in the distal convoluted tubule
Distal convoluted tubule
The distal convoluted tubule is a portion of kidney nephron between the loop of Henle and the collecting duct system.- Physiology :It is partly responsible for the regulation of potassium, sodium, calcium, and pH...

 of the nephron
The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....

where much glucose has been reabsorbed into the bloodstream, SGLT1 transporters are found. These have a high affinity for glucose and a low capacity. Functioning in conjunction, these two secondary active transporters ensure that only negligible amounts of glucose are wasted through excretion in the urine.
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