Molecular physiology of amylin.
Amylin is a 37-amino acid peptide first isolated, purified, and characterized from the amyloid deposits in the pancrease of type 2 diabetics. It is synthesized and secreted primarily from pancreatic beta cells along with insulin. The ability of amylin to potently reduce insulin-stimulated incorporation of glucose into glycogen in skeletal muscle requires both an intact 2Cys-7Cys disulfide bond and a COOH-terminal amide. Amylin has structural and functional relationships to two other messenger proteins, calcitonin and CGRP. Amylin has relatively potent calcitonin-like activity on bone metabolism and weaker CGRP-like activity on the vasculature. CGRP is a slightly weaker agonist than amylin for metabolic responses. Although rat calcitonins are weak, teleost fish calcitonins are very potent agonists for amylin's metabolic effects. This group of peptides appears to act on a family of related G protein-coupled receptors; several variant calcitonin receptors have recently been cloned and expressed. These receptors appear to be coupled to adenylyl cyclase in many instances; recent evidence supports the view that amylin's effects on skeletal muscle occur, at least in large part, through activation of the cAMP pathway.
Pittner
R A
RA
Amylin Pharmaceuticals, Inc., San Diego, California 92121.
Albrandt
K
K
Beaumont
K
K
Gaeta
L S
LS
Koda
J E
JE
Moore
C X
CX
Rittenhouse
J
J
Rink
T J
TJ
D000595:Amino Acid Sequence; D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002116:Calcitonin / Q000737:chemistry / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism; D008969:Molecular Sequence Data; D012474:Salmon; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide