User:Camille Gaudet/Sandbox 1

From Proteopedia

(Difference between revisions)

Revision as of 01:28, 28 April 2024

Glucose-dependent Insulinotropic Polypeptide Receptor

1 Introduction
- 1.1 History
- 1.2 Biological Role
2 General Structure
3 Associated Diseases
4 Medical Relevance
- 4.1 Tirzepatide

Introduction

History

Interest in pancreatic hormones began at the turn of the 20th century. In 1902, Bayliss and Starling discover a pancreatic secretin involved in regulation of water homeostasis, giving rise to interest in pancreatic hormones. Shortly after, in 1906, Moore et al. hypothesize involvement of gastrointestinal hormone extracts in maintenance of the endocrine pancreas. Jean La Barre purifies glucose-lowering gut extracts in 1929 and characterizes them as incretins, which is short for intestine secretion insulin. Finally, in 1984, gastric inhibitory peptide (GIP) is isolated from porcupine intestine. Although GIP was initially characterized for its gastric inhibitory effects (hence the name), it was also shown that the polypeptide played an integral role in insulin signaling and secretion. Interestingly, it was found that the effect of GIP on insulin levels was still seen in its absence, hinting toward the presence of an additional incretin, which has now been classified as glucagon-like peptide-1 (GLP-1).

Biological Role

Figure 1. The biological roles of GIP and and GLP-1, incretin hormones.

The GIP receptor (GIPR) helps facilitate the transport of glucose into/out of the cell through the stimulation of insulin secretion. ^[1]. GIPR is a type of G-Protein Coupled Receptor (GPCR), and its natural ligand, GIP, serves as an initiator of a cellular signaling cascade, thereby activating adenylyl cyclase and increasing cAMP levels. Subsequently, insulin secretion is stimulated. Insulin, a peptide hormone, is secreted by the pancreas in response to glucose ingestion, allowing intake of glucose into the cell via the Glut2 transporter. In individuals with diabetes, insulin is under-secreted or unresponsive to elevated glucose levels, raising blood glucose levels and resulting in failed glucose transport.

General Structure

Subunit Architecture

Glucose-dependent Insulinotropic Polypeptide

Active Site

Associated Diseases

Medical Relevance

Tirzepatide

Figure 2. Sequence alignment of GLP-1, GIP, and Tirzepatide. Residues shown in black are found in all three amino acid sequences. Pink or red coloration denotes residues that are unique to GIP or GLP-1, respectively. The sequence of tirzepatide is colored accordingly, and residues differing from both GIP and GLP-1 are highlighted in blue. Residues that differ across all three structures are boxed.

References

^[1]

↑ ^1.0 ^1.1 Sun B, Willard FS, Feng D, Alsina-Fernandez J, Chen Q, Vieth M, Ho JD, Showalter AD, Stutsman C, Ding L, Suter TM, Dunbar JD, Carpenter JW, Mohammed FA, Aihara E, Brown RA, Bueno AB, Emmerson PJ, Moyers JS, Kobilka TS, Coghlan MP, Kobilka BK, Sloop KW. Structural determinants of dual incretin receptor agonism by tirzepatide. Proc Natl Acad Sci U S A. 2022 Mar 29;119(13):e2116506119. PMID:35333651 doi:10.1073/pnas.2116506119

Student Contributors

Camille Gaudet

Proteopedia Page Contributors and Editors (what is this?)

Camille Gaudet

Retrieved from "http://52.214.119.220/wiki/index.php/User:Camille_Gaudet/Sandbox_1"

@@ Line 8: / Line 8: @@
 === Biological Role ===
-[[Image:GIP-GLP1-Purpose.png|300 px|right|thumb|Figure 1. The biological roles of GIP and and GLP-1, incretin hormones.]] The GIP receptor (GIPR) helps facilitate the transport of glucose into/out of the cell through the stimulation of insulin secretion. <ref name='Sun'>PMID:35333651</ref>. GIPR is a type of [https://en.wikipedia.org/wiki/G_protein-coupled_receptor G-Protein Coupled Receptor] (GPCR), and its natural ligand, GIP, serves as an initiator of a cellular signaling cascade, activating adenylyl cyclase and subsequently potentiating insulin secretion. [https://en.wikipedia.org/wiki/Insulin Insulin], a peptide hormone, is secreted by the pancreas in response to glucose ingestion, allowing intake of glucose into the cell via the [https://en.wikipedia.org/wiki/GLUT2 Glut2] transporter.
+[[Image:GIP-GLP1-Purpose.png|300 px|right|thumb|Figure 1. The biological roles of GIP and and GLP-1, incretin hormones.]] The GIP receptor (GIPR) helps facilitate the transport of glucose into/out of the cell through the stimulation of insulin secretion. <ref name='Sun'>PMID:35333651</ref>. GIPR is a type of [https://en.wikipedia.org/wiki/G_protein-coupled_receptor G-Protein Coupled Receptor] (GPCR), and its natural ligand, GIP, serves as an initiator of a cellular signaling cascade, thereby activating adenylyl cyclase and increasing cAMP levels. Subsequently, insulin secretion is stimulated. [https://en.wikipedia.org/wiki/Insulin Insulin], a peptide hormone, is secreted by the pancreas in response to glucose ingestion, allowing intake of glucose into the cell via the [https://en.wikipedia.org/wiki/GLUT2 Glut2] transporter. In individuals with diabetes, insulin is under-secreted or unresponsive to elevated glucose levels, raising blood glucose levels and resulting in failed glucose transport.
-Once the levels become too high, the ligand will send this transporter back down into the cell and not have anymore glucose activate. It will also cause the insulin pathway to start to help signal that there is too much glucose in the body. As mentioned above, many issues that arise with diabetes can affect the rate of transport within these transporters for the cell.