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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 with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
. The two ways in which glucose uptake can take place are facilitated diffusion (a passive process) and secondary active transport (an active process which on the ion-gradient which is established through the hydrolysis of ATP, known as primary
active transport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...
). Active transport is the movement of ions or molecules going against the concentration gradient. __TOC__


Facilitated diffusion

There are over 10 different types of glucose transporters; however, the most significant for study are GLUT1-4.
GLUT1 Glucose transporter 1 (or GLUT1), also known as solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1), is a uniporter protein that in humans is encoded by the ''SLC2A1'' gene. GLUT1 facilitates the transport of glucose across ...
and GLUT3 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 ( 5 millimolar). 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.
GLUT2 Glucose transporter 2 (GLUT2) also known as solute carrier family 2 (facilitated glucose transporter), member 2 (SLC2A2) is a transmembrane carrier protein that enables protein facilitated glucose movement across cell membranes. It is the principa ...
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 parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...
s and
pancreatic The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an endocr ...
beta cell Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are di ...
s (in mice, but GLUT1 in human beta cells; see Reference 1). The high Km of GLUT2 allows for glucose sensing; rate of glucose entry is proportional to blood glucose levels.
GLUT4 Glucose transporter type 4 (GLUT4), also known as solute carrier family 2, facilitated glucose transporter member 4, is a protein encoded, in humans, by the ''SLC2A4'' gene. GLUT4 is the insulin-regulated glucose transporter found primarily in a ...
transporters are insulin sensitive, and are found in muscle and
adipose Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular ...
tissue. As muscle is a principal storage site for glucose and adipose tissue for
triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''wikt:tri-#Prefix, tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other ...
(into which glucose can be converted for storage), GLUT4 is important in
post-prandial Prandial relates to a meal. Postprandial (from post prandium) means after eating a meal, while preprandial is before a meal. Usages of postprandial The term ''postprandial'' is used in many contexts. Gastronomic or social Refers to activities p ...
uptake of excess glucose from the bloodstream. Moreover, several recent papers show that GLUT 4 is present in the brain also. The drug
metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
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 in
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
ic vesicles within the cell. After a meal and at the binding of insulin (released from the
islets of Langerhans The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% of ...
) to receptors on the cell surface, a signalling cascade begins by activating phosphatidylinositolkinase activity 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 simple cuboidal 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+ 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 any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolys ...
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, N.A., Na, nA or n/a may refer to: Chemistry and physics * Sodium, symbol Na, a chemical element * Avogadro constant (''N''A) * Nucleophilic addition, a type of reaction in organic chemistry * Numerical aperture, a number that characterizes a ...
; this leaves a relative deficiency of Na+ in the intracellular compartment. Na+ ions diffuse down their concentration gradient into the columnar epithelia,
co-transport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...
ing 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 In Cellular Biology, cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane Second law of thermodynamics, from a region of lower concentration to a region of higher concentration—against the concentra ...
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 ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to: * the filter ...
, where glucose levels are high, SGLT2 has a low affinity yet high capacity for glucose transport. Close to the
loop of Henle In the kidney, the loop of Henle () (or Henle's loop, Henle loop, nephron loop or its Latin counterpart ''ansa nephroni'') is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after its ...
and in the
distal convoluted tubule The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule. Physiology It is partly responsible for the regulation of potassium, sodium, calcium, and pH. On its apical surface (lumen ...
of the
nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ...
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.


References

1. De Vos, A., H. Heimberg, et al. (1995). "Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression." The Journal of Clinical Investigation 96(5): 2489–2495. {{DEFAULTSORT:Glucose Uptake Endocrinology