Sulfonylurea receptor
Encyclopedia
In the field of molecular biology
, the sulfonylurea receptors (SUR) are membrane protein
s which are the molecular targets of the sulfonylurea
class of antidiabetic drugs whose mechanism of action is to promote insulin
release from pancreatic
beta cell
s. More specifically, SUR proteins are subunits of the inward-rectifier potassium ion channel
s Kir6.x (6.1 and 6.2
). The association of four Kir6.x and four SUR subunits form an ion conducting channel commonly referred to as the KATP channel.
There are three forms of the sulfonylurea receptor, SUR1
encoded by the ABCC8 gene and SUR2A
and SUR2B
which are splice variants arising from a single ABCC9 gene.
s ATP
and ADP
and in response facilitate the open or closing its associated Kir6.x potassium channel. Hence the KATP channel monitors the energy balance within the cell.
Depending on the tissue in which the KATP channel is expressed, altering the membrane potential can trigger a variety of down stream events. For example, in pancreatic beta cell
s, high levels of glucose lead to increased production of ATP which in turn binds to the KATP channel resulting in channel closure. The reduction in membrane potential in turn opens voltage-dependent calcium channel
s increasing intracellular calcium concentrations which triggers exocytosis
of insulin
.
and susceptibility to type 2 diabetes.
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
, the sulfonylurea receptors (SUR) are membrane protein
Membrane protein
A membrane protein is a protein molecule that is attached to, or associated with the membrane of a cell or an organelle. More than half of all proteins interact with membranes.-Function:...
s which are the molecular targets of the sulfonylurea
Sulfonylurea
Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide...
class of antidiabetic drugs whose mechanism of action is to promote insulin
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....
release from pancreatic
Pancreas
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. More specifically, SUR proteins are subunits of the inward-rectifier potassium ion channel
Inward-rectifier potassium ion channel
Inwardly rectifying potassium channels are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types...
s Kir6.x (6.1 and 6.2
Kir6.2
Kir6.2 is a major subunit of the ATP-sensitive K+ channel, an inward-rectifier potassium ion channel. The gene encoding the channel is called KCNJ11 and mutations in this gene are associated with congenital hyperinsulinism.-Structure:...
). The association of four Kir6.x and four SUR subunits form an ion conducting channel commonly referred to as the KATP channel.
There are three forms of the sulfonylurea receptor, SUR1
ABCC8
ATP-binding cassette transporter sub-family C member 8 is a protein that in humans is encoded by the ABCC8 gene. ABCC8 orthologs have been identified in all mammals for which complete genome data are available.-External links:* *...
encoded by the ABCC8 gene and SUR2A
ABCC9
ATP-binding cassette, sub-family C member 9 also known as sulfonylurea receptor 2 is a ATP-binding cassette transporter that in humans is encoded by the ABCC9 gene.- Function :...
and SUR2B
ABCC9
ATP-binding cassette, sub-family C member 9 also known as sulfonylurea receptor 2 is a ATP-binding cassette transporter that in humans is encoded by the ABCC9 gene.- Function :...
which are splice variants arising from a single ABCC9 gene.
Function
The primary function of the sulfonylurea receptor is to sense intracellular levels of the nucleotideNucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
s 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...
and ADP
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...
and in response facilitate the open or closing its associated Kir6.x potassium channel. Hence the KATP channel monitors the energy balance within the cell.
Depending on the tissue in which the KATP channel is expressed, altering the membrane potential can trigger a variety of down stream events. For example, in pancreatic 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, high levels of glucose lead to increased production of ATP which in turn binds to the KATP channel resulting in channel closure. The reduction in membrane potential in turn opens voltage-dependent calcium channel
Voltage-dependent calcium channel
Voltage-dependent calcium channels are a group of voltage-gated ion channels found in excitable cells with a permeability to the ion Ca2+...
s increasing intracellular calcium concentrations which triggers exocytosis
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...
of insulin
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....
.
Tissue distribution
The isoforms of the sulfonylurea receptor have the following tissue distribution:- adipose tissueAdipose tissueIn histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
- SUR2B/Kir6.1 - pancreatic beta cellBeta cellBeta 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 - SUR1/Kir6.2Kir6.2Kir6.2 is a major subunit of the ATP-sensitive K+ channel, an inward-rectifier potassium ion channel. The gene encoding the channel is called KCNJ11 and mutations in this gene are associated with congenital hyperinsulinism.-Structure:... - cardiac myocytes - SUR2A
- skeletal muscleSkeletal muscleSkeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
- SUR2A - smooth muscleSmooth muscleSmooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
- SUB2B
Disease linkage
The SUR1 protein is coded by the ABCC8 gene and is associated with congenital hyperinsulinismCongenital hyperinsulinism
Congenital hyperinsulinism is a medical term referring to a variety of congenital disorders in which hypoglycemia is caused by excessive insulin secretion. Congenital forms of hyperinsulinemic hypoglycemia can be transient or persistent, mild or severe. These conditions are present at birth and...
and susceptibility to type 2 diabetes.