Regulation of insulin secretion and blood glucose metabolism by adrenomedullin.
Adrenomedullin (AM), a recently discovered hypotensive peptide, is expressed in the endocrine pancreas of different species, as demonstrated by immunocytochemistry. Electron microscopic studies with double immunogold showed colocalization of AM and pancreatic polypeptide. A homogeneous expression of AM receptor was found throughout the islet using in situ hybridization. Six different insulin- producing cell lines have been analyzed by reverse transcription-PCR and showed expression of both AM and its receptor. Two experimental models have been used to study the effects of AM in pancreatic physiology. 1) Analysis of isolated rat islets shows that AM inhibits insulin secretion in a dose-dependent manner. The monoclonal antibody MoAb-G6, which neutralizes AM bioactivity, was able to increase insulin release 5-fold; this effect was reversed by the addition of synthetic AM. 2) Oral glucose tolerance tests showed that iv injection of AM reduces the levels of insulin in the bloodstream with a concomitant increase in circulating glucose. These studies implicate AM as a newly defined factor of the insulin regulatory system that could be involved in disorders such as diabetes and obesity.
Martínez
A
A
Biomarkers and Prevention Research Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850, USA. martineza@bprb.nci.nih.gov
Weaver
C
C
López
J
J
Bhathena
S J
SJ
Elsasser
T H
TH
Miller
M J
MJ
Moody
T W
TW
Unsworth
E J
EJ
Cuttitta
F
F
D053607:Adrenomedullin; D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism*; D002415:Cats; D002460:Cell Line; D006224:Cricetinae; D004285:Dogs; D005951:Glucose Tolerance Test; D006168:Guinea Pigs; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D010455:Peptides / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D001786:Blood Glucose; D007328:Insulin; D010455:Peptides; D012333:RNA, Messenger; D053607:Adrenomedullin