Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin converting enzyme (ACE) plays an essential role in two physiological systems, one leading to the production of angiotensin II and the other to the degradation of bradykinin. The wide distribution and multifunctional properties of these peptides suggest that ACE could be involved in various pathophysiological conditions. The discovery that ACE levels are under genetic control ushered in a new era of investigation; most studies focused on an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene as a marker for a functional polymorphism. Recently, many single nucleotide polymorphisms were detected in the gene and the search for the locations of functional polymorphisms became a topic of extensive investigation. Nevertheless, association studies on the I/D polymorphism and clinical outcomes continued, mostly with conflicting results. This article reviews the current state of knowledge regarding ACE polymorphisms and suggests that a functional polymorphism is most likely located between intron 18 and the 3' UTR. The potential existence of another functional polymorphism in the 5' UTR, however, cannot be excluded. This review also presents an overview of ACE function in different pathophysiological systems, and summarizes previous reports on ACE and clinical outcomes. Although findings on the I/D polymorphism and disorders like diabetic nephropathy and Alzheimer disease can be considered conclusive, reports on most of the cardiovascular phenotypes are still controversial. Genotypic and phenotypic misclassifications, insufficient power in some studies, and the presence of interaction with other genes or environmental factors are possible explanations for the contradictory findings.
 ...
PMID:ACE polymorphisms. 1669 Aug 93

Amylin (islet amyloid peptide) plays a critical role in islet amyloidosis and in the development of beta-cell dysfunction in patients with diabetes; however, the involvement of amylin in renal amyloidosis has not been studied. For this reason, we surveyed 149 patients with biopsy-proven diabetic nephropathy (DN). The results were compared to 95 renal disease control patients, which included membranoproliferative glomerulonephritis, light-chain deposition, IgA nephropathy, and obesity-related glomerulopathy (ORG). Seventy-two of the 149 patients with DN showed amylin deposition in their renal tissue. Amylin was mainly distributed in the expanded mesangial area, Kimmelstiel-Wilson nodules, Bowman's capsule, and in blood vessels. The frequencies of mesangial proliferation, glomerular nodule lesions, and glomerular sclerosis were higher in DN patients with amylin deposits. Furthermore, the tubular interstitial lesions were more severe in these patients. Of the 95 disease-control patients, four with ORG were positive for renal amylin deposits. Our study has found renal amylin deposition in patients with DN and that the deposition was associated with disease severity. We suggest that strict metabolic control and reversing insulin resistance in patients with diabetes may blunt the process of amylin deposition in the kidney and possibly protect renal function in these patients.
 ...
PMID:Amylin deposition in the kidney of patients with diabetic nephropathy. 1749 60

A variety of peptide signaling moieties that we have termed intracrines can act in the interiors of their cells of synthesis or of target cells after internalization. These intracrine factors are known to be upregulated in such disorders as diabetic nephropathy, systolic heart failure, and age-related macular degeneration. Indeed, a similar set of intracrines is upregulated in each of these disorders, suggesting a commonality of mechanism. In addition, several chronic neurodegenerative disorders such as Alzheimer disease and Parkinson disease involve intercellular trafficking of intracellular disease-causing proteins. These disorders can be considered intracrine-like. Here the mechanistic and therapeutic implications of these observations, and of the relevant modes of intracrine action, are discussed, including the possibility that similar therapeutic approaches could be effective in multiple progressive disorders and the implications of these observations for intracrine pharmacology in general.
 ...
PMID:A Pathogenic Mechanism Potentially Operative in Multiple Progressive Diseases and Its Therapeutic Implications. 2888 62