Rat amylin: cloning and tissue-specific expression in pancreatic islets.
Amyloid deposits in the islets of Langerhans of the pancreas are a common finding in non-insulin-dependent diabetes mellitus. The main protein constituent of these deposits is a 37-amino acid peptide known as amylin that resembles calcitonin gene-related peptide, a neuropeptide. We have isolated cDNA clones corresponding to the rat amylin precursor from an islet cDNA library and we show that this peptide is encoded in a 0.9-kilobase mRNA that is translated to yield a 93-amino acid precursor. The amylin peptide is bordered by dibasic residues, suggesting that it is proteolyzed like calcitonin gene-related peptide. The peptide sequences flanking the amylin sequence do not resemble the calcitonin gene-related peptide flanking sequences. RNA hybridization studies show that amylin mRNA is abundant in the islets of Langerhans but is not present in the brain or seven other tissues examined. Dietary changes, such as fasting or fasting and refeeding, have little effect on amylin mRNA expression. This tissue specificity suggests that amylin is involved in specific signaling pathways related to islet function.
Leffert
J D
JD
Gifford Laboratories, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, 75235.
Newgard
C B
CB
Okamoto
H
H
Milburn
J L
JL
Luskey
K L
KL
D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015740:Calcitonin Gene-Related Peptide; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015342:DNA Probes; D005786:Gene Expression Regulation; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics; D009693:Nucleic Acid Hybridization; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution
D000682:Amyloid; D015342:DNA Probes; D058228:Islet Amyloid Polypeptide; D009479:Neuropeptides; D011498:Protein Precursors; D012333:RNA, Messenger; D004247:DNA; D015740:Calcitonin Gene-Related Peptide