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).

General Structure

Subunit Architecture

Glucose-dependent Insulinotropic Polypeptide

Active Site

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Associated Diseases

Medical Relevance

Tirzepatide

Figure 2. Sequence alignment of GLP-1, GIP, and Tirzepatide. Residues shown in black are found in all three polypeptides, and modified residues in tirzepatide are highlighted in blue. Residues shown in pink and red are unique to GIP and GLP-1 respectively.