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Title: IS ADRENOMEDULLIN A CAUSAL AGENT IN SOME CASES OF TYPE 2 DIABETES?

Author
item MARTINEZ, ALFREDO - NIH, BETHESDA, MD
item Elsasser, Theodore
item Bhathena, Sam
item PIO, RUBEN - NIH, BETHESDA, MD
item BUCHANAN, THOMAS - UNIV. SOUTHERN CALIFORNIA
item MACRI, CHARLES - USUHS, BETHESDA, MD
item CUTTITTA, FRANK - NIH, BETHESDA, MD

Submitted to: Peptides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/6/1999
Publication Date: N/A
Citation: N/A

Interpretive Summary: Diabetes is the leading metabolic disorder challenging the quality of life for more than 16 million people in the United States. While the condition is defined by an absence or reduced release of the hormones that regulate sugar use by tissues and the loss of control of sugar use by tissues in the body, there appears to be several causes for why the release of the hormones is poor. While doctors strive to help diabetics live more normal lives and pursue life's activities, it is clear that some people respond to traditional treatment with diminishing response and this challenges doctors to decide what other ways this condition can be treated. We have discovered that within the larger population of diabetics, other subpopulations may be present that can be further defined by other underlying conditions that themselves may trigger the diabetic condition. In previous research we demonstrated that the natural hormone adrenomedullin can slow insulin release and cause the increased plasma concentrations of the sugar glucose that together are the hallmarks for diabetes. In the present research we clearly show that some individuals have increased concentrations of adrenomedullin. In an animal model of diabetes where concentrations of adrenomedullin in the circulation are high, where we have given compounds that reduce and control the release of adrenomedullin, we have corrected the diabetic condition. The research is significant in that it offers a way to detect a population of diabetics in which the disease is caused by an associated but different pathology. The approach to managing diabetes needs to include screening for adrenomedullin and by controlling the over secretion of this hormone, one can more efficiently manage some of the problems of metabolism associated with diabetes.

Technical Abstract: The study of two populations with a recent onset of type-2 diabetes showed that a subset of the patients had higher plasma levels of adrenomedullin (AM) than the rest of the diabetics. In this subset, physiological increases in AM might have triggered the disease in predisposed individuals. Diabetics showed higher levels of AM than healthy controls. In addition, glycemia was measured in genetically diabetic rats after injection with saline, AM or antibody against AM. AM administration increased plasma glucose levels, while the antibody reduced circulating glucose concentrations to normal. These results suggest that manipulation of AM levels could represent a new approach to management of diabetes in appropriate individuals.