Target type: molecularfunction
Combining with sulfonylurea, and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. [GOC:ai, GOC:signaling]
Sulfonylurea receptor (SUR) activity is a crucial molecular function involved in the regulation of insulin secretion from pancreatic beta cells. SUR proteins are transmembrane subunits of ATP-sensitive potassium (KATP) channels, which are essential for maintaining beta cell electrical excitability and insulin release.
SUR proteins exist as two isoforms, SUR1 and SUR2, with SUR1 primarily expressed in pancreatic beta cells, heart, and skeletal muscle, while SUR2 is predominantly found in the brain and other tissues. In pancreatic beta cells, SUR1 forms a complex with the inward rectifier potassium channel Kir6.2, creating the KATP channel.
The primary role of SUR1 in KATP channels is to act as a regulatory subunit, binding to sulfonylureas, a class of drugs used to treat type 2 diabetes. Sulfonylureas bind to SUR1 and inhibit the channel's activity, leading to depolarization of the beta cell membrane, an increase in intracellular calcium levels, and ultimately, insulin release.
Specifically, sulfonylurea binding to SUR1 induces conformational changes in the protein, which in turn affects the channel's permeability to potassium ions. This inhibition of KATP channel activity results in a decrease in potassium efflux from the beta cell, leading to membrane depolarization. Depolarization then triggers the opening of voltage-gated calcium channels, allowing calcium influx into the cell. The rise in intracellular calcium concentration initiates a cascade of events that ultimately lead to the release of insulin from intracellular storage vesicles.
In summary, sulfonylurea receptor activity is an essential molecular function that plays a critical role in insulin secretion from pancreatic beta cells. By binding to SUR1 and inhibiting the KATP channel, sulfonylureas promote beta cell depolarization, calcium influx, and ultimately, insulin release, providing a therapeutic target for the treatment of type 2 diabetes.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| ATP-binding cassette sub-family C member 8 | An ATP-binding cassette sub-family C member 8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q09428] | Homo sapiens (human) |
| ATP-binding cassette sub-family C member 9 | An ATP-binding cassette sub-family C member 9 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O60706] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| diazoxide | diazoxide : A benzothiadiazine that is the S,S-dioxide of 2H-1,2,4-benzothiadiazine which is substituted at position 3 by a methyl group and at position 7 by chlorine. A peripheral vasodilator, it increases the concentration of glucose in the plasma and inhibits the secretion of insulin by the beta- cells of the pancreas. It is used orally in the management of intractable hypoglycaemia and intravenously in the management of hypertensive emergencies. Diazoxide: A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group. | benzothiadiazine; organochlorine compound; sulfone | antihypertensive agent; beta-adrenergic agonist; bronchodilator agent; cardiotonic drug; diuretic; K-ATP channel agonist; sodium channel blocker; sympathomimetic agent; vasodilator agent |
| glyburide | glyburide : An N-sulfonylurea that is acetohexamide in which the acetyl group is replaced by a 2-(5-chloro-2-methoxybenzamido)ethyl group. Glyburide: An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide | monochlorobenzenes; N-sulfonylurea | anti-arrhythmia drug; EC 2.7.1.33 (pantothenate kinase) inhibitor; EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor; hypoglycemic agent |
| pinacidil | Pinacidil: A guanidine that opens POTASSIUM CHANNELS producing direct peripheral vasodilatation of the ARTERIOLES. It reduces BLOOD PRESSURE and peripheral resistance and produces fluid retention. (Martindale The Extra Pharmacopoeia, 31st ed) | pyridines | |
| propafenone | propafenone : An aromatic ketone that is 3-(propylamino)propane-1,2-diol in which the hydrogen of the primary hydroxy group is replaced by a 2-(3-phenylpropanoyl)phenyl group. It is a class 1C antiarrhythmic drug with local anesthetic effects, and is used as the hydrochloride salt in the management of supraventricular and ventricular arrhythmias. Propafenone: An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. | aromatic ketone; secondary alcohol; secondary amino compound | anti-arrhythmia drug |
| troglitazone | Troglitazone: A chroman and thiazolidinedione derivative that acts as a PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR) agonist. It was formerly used in the treatment of TYPE 2 DIABETES MELLITUS, but has been withdrawn due to hepatotoxicity. | chromanes; thiazolidinone | anticoagulant; anticonvulsant; antineoplastic agent; antioxidant; EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor; ferroptosis inhibitor; hypoglycemic agent; platelet aggregation inhibitor; vasodilator agent |
| n-cyano-n'-(1,1-dimethylpropyl)-n''-(3-pyridinyl)guanidine | N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine: potassium channel opener | pyridines | |
| repaglinide | piperidines | ||
| cromakalim | Cromakalim: A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352) | ||
| rosiglitazone | aminopyridine; thiazolidinediones | EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor; ferroptosis inhibitor; insulin-sensitizing drug | |
| mk 767 | 5-((2,4-dioxo-5-thiazolidinyl)methyl)-2-methoxy-N-((4-(trifluoromethyl)phenyl)methyl)benzamide: an antihyperlipidemic agent that also functions as an insulin sensitizer, PPARalpha agonist, and PPARgamma agonist; structure in first source | ||
| zeneca zd 6169 | Zeneca ZD 6169: an ATP-sensitive potassium channel opener; structure given in first source | ||
| cromakalim | 1-benzopyran | ||
| clamikalant | clamikalant: inhibits ATP-sensitive potassium channel; structure in first source | ||
| zm226600 | ZM226600: an ATP-sensitive potassium channel opener; structure in first source | anilide | |
| way 133537 | |||
| ly 465608 | LY 465608: a nonthiazolidinedione agonist of both PPAR-alpha and PPAR-gamma of Ligand Pharm. and Eli Lilly | ||
| bm 131246 | |||
| nn 414 | NN 414: a hypoglycemic agent with insulin release modulating and potassium channel activating activities; structure in first source | ||
| 7-chloro-3-isopropylamino-4h-1,2,4-benzothiadiazine 1,1-dioxide | 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide: activates ATP-sensitive potassium channels; structure in first source |