Activity of Pramlintide, Rat and Human Amylin but Not Aβ1-42 at Human Amylin Receptors

Endocrinology. 2014 Jan;155(1):21-6. doi: 10.1210/en.2013-1658. Epub 2013 Dec 20.

Abstract

Amylin is a neuroendocrine hormone involved in glucose regulation. An amylin analog, pramlintide, is used to treat insulin-requiring diabetes. Its anorexigenic actions give it potential as an obesity treatment. There are 3 amylin receptors (AMY1, AMY2, AMY3), comprising the calcitonin receptor and receptor activity-modifying proteins 1, 2, and 3, respectively. The pharmacology of pramlintide at each subtype has not been determined whereas the unrelated peptide β-amyloid 1-42 (Aβ1-42) has recently been proposed to be a specific agonist of the AMY3 receptor. We investigated the actions of Aβ1-42 and pramlintide, compared with human and rat amylin at the calcitonin receptor, AMY1, AMY2, and AMY3 receptors, measuring the cAMP response in human embryonic kidney 293S and Cos 7 cells. Pramlintide activated all receptors with a slight preference for AMY1. No cAMP response was detected with Aβ1-42 at any receptor, suggesting that it may not be a genuine agonist of AMY receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amylin Receptor Agonists
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • COS Cells
  • Calcitonin / metabolism
  • Chlorocebus aethiops
  • HEK293 Cells
  • Humans
  • Hypoglycemic Agents / chemistry*
  • Islet Amyloid Polypeptide / chemistry
  • Islet Amyloid Polypeptide / metabolism*
  • Molecular Sequence Data
  • Peptide Fragments / metabolism*
  • Phenotype
  • Rats
  • Receptors, Calcitonin / agonists
  • Receptors, Calcitonin / metabolism
  • Receptors, Islet Amyloid Polypeptide / metabolism*

Substances

  • Amylin Receptor Agonists
  • Amyloid beta-Peptides
  • Hypoglycemic Agents
  • Islet Amyloid Polypeptide
  • Peptide Fragments
  • Receptors, Calcitonin
  • Receptors, Islet Amyloid Polypeptide
  • amyloid beta-protein (1-42)
  • Calcitonin
  • pramlintide