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Title: REGULATION OF INSULIN SECRETION AND BLOOD GLUCOSE METABOLISM BY ADRENOMEDULLIN

Author
item MARTINEZ, A - NIH, NATIONAL CANCER INST
item WEAVER, C - NIH, NATIONAL CANCER INST
item LOPEZ, J - NIH, NATIONAL CANCER INST
item BHATHENA, J - NIH, NATIONAL CANCER INST
item Elsasser, Theodore
item MILLER, M - NIH, NATIONAL CANCER INST
item MOODY, T - NIH, NATIONAL CANCER INST
item UNSWORTH, E - NIH, NATIONAL CANCER INST
item CUTTITTA, F - NIH, NATIONAL CANCER INST

Submitted to: Journal of Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/5/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: Many diseases of metabolism are associated with poor levels of secretion of the hormone insulin. While there are many known and well characterized manifestations of insulin secretion malfunction such as type I and type 2 diabetes, there are many forms of diabetes and improper glucose metabolism and utilization that are clinically observed but without a readily apparent source of cause. Causes of insulin secretion defects can be associated with failure of natural regulatory mechanisms to function properly. We have recently conducted experiments that show a newly discovered hormone called adrenomedullin (AM) can regulate secretion of insulin from the pancreas. Specifically AM decreases secretion of insulin. It is possible that one or more mistakes in the failure of insulin to be released in diabetes may be related to AM. Because we now recognize AM to play a role in insulin secretion in normal animals, we can explore this hormone in disease states and determine if AM plays a role in pancreatic malfunction. Further research is being undertaken to better understand the regulation of AM in the pancreas so that if AM plays a role in some forms of diabetes, we will have knowledge of how best to regulate AM.

Technical Abstract: Adrenomedullin (AM), a recently discovered hypotensive peptide, is expressed in the endocrine pancreas of different species as demonstrated by immunohistochemisry . Electron microscope studies with double immunogold showed colocalization of AM and pancreatic polypeptide. A homogeneous expression of AM receptor (AM-r) was found throughout he islets using in situ hybridization. Six different insulin-producing cell lines were analyzed by RT- PCR and showed expression of both AM and AM-r. Two experimental models have been used to study the effects of AM in pancreatic physiology: 1) analysis of rat islets showed that AM inhibits insulin secretion in a dose-dependent manner. The monoclonal AB MoAB - G6 , which neutralizes AM bioactivity, was able to increase insulin release 5-fold. This effect was reversed by the addition of AM to the media. 2) Oral glucose tolerance tests showed that iv injection of synthetic AM reduced peak levels of insulin with a concomitant increase in peak concentrations of glucose in the circulation. 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.