The hypothalamic satiety peptide CART is expressed in anorectic and non-anorectic pancreatic islet tumors and in the normal islet of Langerhans.
The hypothalamic satiety peptide CART (cocaine and amphetamine regulated transcript) is expressed at high levels in anorectic rat glucagonomas but not in hypoglycemic insulinomas. However, a non-anorectic metastasis derived from the glucagonoma retained high CART expression levels and produced circulating CART levels comparable to that of the anorectic tumors. Moreover, distinct glucagonoma lines derived by stable HES-1 transfection of the insulinoma caused severe anorexia but retained low circulating levels of CART comparable to that of insulinoma bearing or control rats. Islet tumor associated anorexia and circulating CART levels are thus not correlated, and in line with this peripheral administration of CART (5-50 mg/kg) produced no effect on feeding behavior. In the rat two alternatively spliced forms of CART mRNA exist and quantitative PCR revealed expression of both forms in the hypothalamus, in the different islet tumors, and in the islets of Langerhans. Immunocytochemistry as well as in situ hybridization localized CART expression to the somatostatin producing islet D cell. A potential endocrine/paracrine role of islet CART remains to be clarified.
Jensen
P B
PB
Hagedorn Research Institute, Department of Developmental Biology, Gentofte, Denmark.
Kristensen
P
P
Clausen
J T
JT
Judge
M E
ME
Hastrup
S
S
Thim
L
L
Wulff
B S
BS
Foged
C
C
Jensen
J
J
Holst
J J
JJ
Madsen
O D
OD
D007516:Adenoma, Islet Cell / Q000097:blood* / Q000235:genetics*; D000818:Animals; D000855:Anorexia / Q000097:blood* / Q000235:genetics*; D001483:Base Sequence; D015342:DNA Probes / Q000235:genetics; D004435:Eating / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D005935:Glucagonoma / Q000097:blood / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007340:Insulinoma / Q000097:blood / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000097:blood* / Q000235:genetics* / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D051381:Rats; D019864:Somatostatin-Secreting Cells / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D015342:DNA Probes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein