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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clustering of diseases has been appreciated by health insurers and epidemiologists for some time. Co-morbidity suggests shared pathways of disease. It is by now well agreed that common diseases have a strong genetic component. Here we present evidence that the angiotensin I-converting enzyme (ACE) deletion/deletion (D/D) genotype is associated with a large number of common adult diseases, including cardiovascular disease, cancer, and psychiatric disease. Since the ACE D/D genotype has been shown to be associated with increased levels of tissue ACE expression at the protein level, these data suggest that overactivity of ACE may be involved in the pathogenesis of common diseases, as well as the utility of effective ACE inhibition in their treatment and, perhaps, prevention.
Diabetes Technol Ther 2002
PMID:Is angiotensin I-converting enzyme a "master" disease gene? 1245 70

Diabetes mellitus impairs the cardiac kallikrein-kinin system by reducing cardiac kallikrein (KLK) and kininogen levels, a mechanism that may contribute to the deleterious outcome of cardiac ischemia in this disease. We studied left ventricular (LV) function and bradykinin (BK) coronary outflow in buffer-perfused, isolated working hearts (n = 7) of controls and streptozotocin (STZ)-induced diabetic rats before and after global ischemia. With the use of selective kininase inhibitors, the activities of angiotensin I-converting enzyme, aminopeptidase P, and neutral endopeptidase were determined by analyzing the degradation kinetics of exogenously administered BK during sequential coronary passages. Basal LV function and coronary flow were impaired in STZ-induced diabetic rats. Neither basal nor postischemic coronary BK outflow differed between control and diabetic hearts. Reperfusion after 15 min of ischemia induced a peak in coronary BK outflow that was of the same extent and duration in both groups. In diabetic hearts, total cardiac kininase activity was reduced by 41.4% with an unchanged relative kininase contribution compared with controls. In conclusion, despite reduced cardiac KLK synthesis, STZ-induced diabetic hearts are able to maintain kinin liberation under basal and ischemic conditions because of a primary impairment or a secondary downregulation of kinin-degrading enzymes.
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PMID:Cardiac kinin level in experimental diabetes mellitus: role of kininases. 1263 59

"Somatic" angiotensin I-converting enzyme (ACE) appears to be one of the evolutionary advances that made a closed circulation possible, and may have contributed to the Cambrian "explosion" of species approximately 540 million years ago. It also appears to be at the origin of a large number of common human diseases. A model is proposed in which the duplicated form of ACE ("somatic" ACE) functions as a mechanotransducer, defending downstream vessels and tissues from an increase in pressure. In the model, ACE senses shear stress (blood velocity) in regions of turbulent blood flow. An increase in shear stress strips an autoinhibitor tripeptide, FQP, from the N-terminal active site, thereby activating it. The C-terminal domain is constitutively activated by chloride. This model explains the clinical superiority of hydrophobic ACE inhibitors relative to hydrophilic ones.
Diabetes Technol Ther 2002
PMID:Is "somatic" angiotensin I-converting enzyme a mechanosensor? 1268 4

If somatic angiotensin I-converting enzyme (ACE) were a mechanosensor, as recently claimed, it would provide insight into the molecular origin of most adult diseases, such as diabetes, cancer, autoimmune diseases, and psychiatric disease, as well as aging itself. The "ACE as mechanosensor" hypothesis holds that tissue ACE is activated by turbulent flow with each heart beat, so that age-dependent diseases begin with a signal from the vasculature. Activation of ACE would thus represent the first of many amplification steps ("cascades"), placing it at the origin of most age-dependent diseases. As a corollary, effective inhibition of tissue ACE might significantly delay the progression of most diseases of aging. In this paper we will explore how useful this hypothesis is in explaining the molecular pathogenesis of diabetes and its complications, in which aging is accelerated.
Diabetes Technol Ther 2003
PMID:Pathophysiologic implications of angiotensin I-converting enzyme as a mechanosensor: diabetes. 1287 9

Endometrial carcinoma is one of the most common gynecological malignancies. Most cases are diagnosed in older patients with diabetes, hypertension, or obesity. The renin-angiotensin system (RAS) has a central role controlling blood pressure and sodium homeostasis. RAS polymorphisms have been reported as genetic determinants of essential hypertension. The objective of this study was to analyze angiotensin I-converting enzyme gene insertion/deletion polymorphism and endometrial human cancer in normotensive and hypertensive women. The presence of an angiotensin converting enzyme (ACE) polymorphism was analyzed by polymerase chain reaction in DNA isolated from peripheral blood samples of 171 women: 70 cases with endometrial cancer (age, 63.6 +/- 9.5 years) and 101 normal control women (age, 61.3 +/- 6.4 years). We detected DD genotype in 47.5%, ID genotype in 44.3%, and II genotype in 8.2% of cases. The allele frequency was 0.69 for D allele and 0.30 for I allele. In normotensives, we found that the presence of I allele (genotypes ID and II) is significantly associated to an earlier age (56.0 +/- 10.1 versus 65.8 +/- 9.9) of onset of endometrial carcinoma (P=0.029). We observed that normotensive women carriers of an allele I have a higher risk of development of endometrial cancer under the age of 63 years (odds ratio=3.60, 95% confidence interval=1.03-12.56; P=0.037). Our findings suggest that ACE polymorphism may be associated with the development of endometrial carcinoma and with the onset of this tumor in younger women. The definition of a pharmacogenomic profile of human neoplasia may help to identify targets for the development of therapeutic or chemoprevention strategies.
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PMID:Angiotensin I-converting enzyme gene insertion/deletion polymorphism and endometrial human cancer in normotensive and hypertensive women. 1552 1

Enzymatic hydrolysates were prepared from bee bread using three proteases. The antioxidant properties of these hydrolysates were measured using four different methods. These had remarkable antioxidant activity similar or superior to that of 1 mM alpha-tocopherol. They also had high scavenging activities against active oxygen species as the superoxide anion radical and hydroxyl radicals. Moreover, they showed angiotensin I-converting enzyme inhibitory activities and the activities were similar to those from various fermented foods such as fish sauce, sake, vinegar, cheese, miso, and natto. The present studies reveal that enzymatic hydrolysates from bee bread are of benefit not only for the materials of health food diets, but also for in patients undergoing various diseases such as cancer, cardiovascular diseases, diabetes, and hypertension.
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PMID:Antioxidant activity and angiotensin I-converting enzyme inhibition by enzymatic hydrolysates from bee bread. 1578 58

Long-term type 2 diabetes can lead to numerous biological complications, such as hypertension and cardio-vascular disease. Key enzymes involved in the enzymatic breakdown of complex carbohydrates,pancreatic alpha-amylase and intestinal alpha-glucosidase, have been targeted as potential avenues for modulation of type 2 diabetes-associated post-prandial hyperglycemia through mild inhibition of their enzymatic activities so as to decrease meal-derived glucose absorption. Further, inhibition of hypertension-linked angiotensin I-converting enzyme (ACE) was targeted as a potential approach for modulation of diabetes-linked hypertension. Water-soluble extracts of soybean optimized for phenolic content via sprouting or bioprocessing by dietary fungus (Rhizopus oligosporus, Lentinus edodes) were investigated for inhibitory activity against porcine pancreatic alpha-amylase (PPA), yeast alpha-glucosidase, and rabbit lung ACE in vitro. PPA was allowed to react with each phenolic-optimized extract and the derivatized enzyme-phytochemical mixtures obtained were characterized for residual amylase activity. Alpha-glucosidase and ACE activities were determined in the presence of each phenolic-optimized extract. All of the soybean extracts possessed marked anti-amylase activity, with extracts of R. oligosporus-bioprocessed soybean having the strongest inhibitory activity, but only slight anti-glucosidase activity. The anti-amylase activity of each extract seemed associated with extract antioxidant activity. Anti-enzyme activity was slightly associated with total soluble phenolic content per se, but seemed more associated to the length of sprouting or bioprocessing of the soybean substrate. Short-term sprouting or bioprocessing seemed to improve anti-amylase activity, while long-term sprouting or bioprocessing seemed to aid anti-glucosidase activity. While ACE activity was strongly inhibited by all of the soybean extracts (44-97%), only sprouting was found to increase this inhibition and bioprocessing of soybean with L. edodes decreased inhibitory activity of soybean extract. The results suggest that sprouting and dietary fungal bioprocessing of soybean improve the anti-diabetic potential of soybean extracts, potentially through modulation of the phenolic profile of the extract, and further suggest that enzyme inhibitory activity may be linked to phenolic antioxidant mobilization during spouting and/ or bioprocessing. The significance of food-grade, plant-based enzyme inhibitors for modulation of carbohydrate breakdown and control of glycemic index of foods in the context of preventing hyperglycemia and diabetes mellitus complications such as hypertension in the long-term is hypothesized and discussed.
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PMID:Anti-diabetic and anti-hypertensive potential of sprouted and solid-state bioprocessed soybean. 1592 31

Metabolic syndrome represents a common risk factor for premature cardiovascular disease and cancer whose core cluster includes diabetes, hypertension, dyslipidaemia and obesity. The liver is a target organ in metabolic syndrome patients in which it manifests itself with non-alcoholic fatty liver disease spanning steatosis through hepatocellular carcinoma via steatohepatitis and cirrhosis. Given that metabolic syndrome and non-alcoholic fatty liver disease affect the same insulin-resistant patients, not unexpectedly, there are amazing similarities between metabolic syndrome and non-alcoholic fatty liver disease in terms of prevalence, pathogenesis, clinical features and outcome. The available drug weaponry for metabolic syndrome includes aspirin, metformin, peroxisome proliferator-activated receptor agonists, statins, ACE (angiotensin I-converting enzyme) inhibitors and sartans, which are potentially or clinically useful also to the non-alcoholic fatty liver disease patient. Studies are needed to highlight the grey areas in this topic. Issues to be addressed include: diagnostic criteria for metabolic syndrome; nomenclature of non-alcoholic fatty liver disease; enlargement of the clinical spectrum and characterization of the prognosis of insulin resistance-related diseases; evaluation of the most specific clinical predictors of metabolic syndrome/non-alcoholic fatty liver disease and assessment of their variability over the time; characterization of the importance of new risk factors for metabolic syndrome with regard to the development and progression of non-alcoholic fatty liver disease.
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PMID:Review article: the metabolic syndrome and non-alcoholic fatty liver disease. 1622 69

Levels of obesity-linked non-insulin-dependent diabetes mellitus (NIDDM) and hypertension are highest among indigenous communities in North America. This is linked to changes in dietary pattern towards high calorie foods such as sugar, refined grain flour, and sweetened beverages. Therefore, a return to traditional dietary patterns may help to reduce these disease problems because of better balance of calories and beneficial nutrients. Further protective non-nutrient phenolic phytochemicals against NIDDM and hypertension are potentially high in these foods but less understood. In this study antidiabetic- and antihypertension-relevant potentials of phenolic phytochemicals were confirmed in select important traditional plant foods of indigenous communities such as pumpkin, beans, and maize using in vitro enzyme assays for -glucosidase, alpha-amylase, and angiotensin I-converting enzyme (ACE) inhibitory activities. In vitro inhibitory activities of these enzymes provide a strong biochemical rationale for further in vivo studies and dietary management strategy for NIDDM through the control of glucose absorption and reduction of associated hypertension. These enzyme inhibitory activities were further compared to total soluble phenolic content and antioxidant activity of the above-targeted plant foods. Pumpkin showed the best overall potential. Among the varieties of pumpkin extracts P5 (round orange) and P6 (spotted orange green) had high content of total phenolics and moderate antioxidant activity coupled to moderate to high alpha-glucosidase and ACE inhibitory activities. Therefore this phenolic antioxidant-enriched dietary strategy using specific traditional plant food combinations can generate a whole food profile that has the potential to reduce hyperglycemia-induced pathogenesis and also associated complications linked to cellular oxidation stress and hypertension.
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PMID:Health benefits of traditional corn, beans, and pumpkin: in vitro studies for hyperglycemia and hypertension management. 1765 Oct 62

The renin-angiotensin aldosterone system (RAAS) is well-established to be involved in diabetic nephropathy. Several abnormalities in the RAAS have been described in diabetes mellitus, including an abnormal aldosterone to renin ratio, elevated angiotensin I-converting enzyme (ACE) levels, and altered angiotensin II sensitivity. Whereas the renoprotective properties of ACE-inhibition in diabetic nephropathy have been demonstrated more than a decade ago, somewhat surprisingly, the role of ACE-activity in the pathogenesis of diabetic nephropathy is not well established. This paper addresses the possible functional impact of genetic and environmental increased in ACE activity in the pathogenesis of diabetic renal damage, in the context of the various other abnormalities in the RAAS in diabetes. Human and experimental data on circulating and tissue ACE in diabetes are reviewed, as well as the associations of ACE with angiotensin I conversion, with pathophysiological responses, and with renal end organ damage. New data from our laboratory provide evidence for interaction between genetical regulation of ACE activity by the ACE (I/D) genotype and diabetes as an environmental factor. Moreover, for functional effects of the elevated ACE activity in terms of increased conversion of angiotensin I to angiotensin II. The effects of enhanced generation of angiotensin II are modulated by the angiotensin II-subtype I receptor (AT1R). Altered AT1R sensitivity has been reported in diabetes that may further modu-late the eventual effects of elevated ACE. Epidemiological data on the association of genetically elevated ACE activity with diabetic nephropathy provide support for a pathogenetic role of elevated ACE activity in diabetic nephropathy. Together, the data suggest that differences in ACE expression and activity, resulting from both genetic and environmental factors and their interaction can modulate the pathogenesis of diabetic nephropathy. Unravelling the nature of this interaction, with focus on modifiable environmental factors, may help to ameliorate the risk for nephropathy in diabetes.
Curr Diabetes Rev 2007 Feb
PMID:Angiotensin I-converting enzyme: a pathogenetic role in diabetic renal damage? 1822 Jun 55


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