Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The present study was undertaken to examine the effect of the angiotensin converting enzyme (ACE) inhibitor, enalapril, on blood pressure and spontaneous blood glucose levels in two rat models: our new diabetic hypertensive rat in which genetic hypertension and diabetes develop following cross-breeding of Cohen diabetic rat (CDR) and spontaneous hypertensive rats (SHR); and a rat in which hypertension, hyperinsulinaemia and hyperlipidaemia were induced by fructose diet. 2. The new strain of animal was fed the usual copper-poor sucrose diet, and for 4 weeks received enalapril. The fructose-induced hyperinsulinaemic animals were fed a fructose-enriched diet for 3 weeks, and enalapril 20 mg per kg per day was added to the drinking water for 2 more weeks. 3. The new strain of diabetic-hypertensive rats that received enalapril showed a significant decrease in blood pressure level. The fructose-fed animals showed a fall in insulin and blood pressure following the introduction of enalapril to their diet. 4. The present study confirms the advantage of the ACE inhibitor enalapril in improving the metabolic parameters of hypertensive diabetic rats, including insulin sensitivity.
 ...
PMID:Enalapril improves glucose tolerance in two rat models: a new hypertensive diabetic strain and a fructose-induced hyperinsulinaemic rat. 907 25

Alterations in the renal dopamine [DA] system have been suggested to contribute to the development of hypertension and diabetic nephropathy. To identify early abnormalities in renal handling of DA and sodium we challenged 16 normotensive patients with uncomplicated insulin-dependent diabetes (IDDM), 18 normotensive nondiabetic subjects with familial borderline hypertension, and 16 healthy controls, 14-29 years old, with a high-sodium diet (HSD). Systolic blood pressure was slightly higher in subjects with familial borderline hypertension than in the other groups on a normal sodium diet (NSD) (P < 0.05). Blood pressure and 24-h urinary measurements were performed on a NSD and after 3 days on a HSD. Twenty-four-hour urinary DA excretion was similar in all groups on NSD. A significant rise in DA excretion was noted after HSD in control subjects (P < 0.01), but not in subjects with a family history of hypertension or with IDDM. Urinary sodium excretion increased in all groups. A correlation between the change in DA and sodium/creatinine ratio after HSD was seen in healthy controls (r = 0.57, P = 0.02) but not in those with familial borderline hypertension (r = 0.18, P = 0.47) or with IDDM (r = 0.40, P = 0.15). A rise in systolic (but not diastolic) pressure was noted only in the IDDM group after HSD (P = 0.02). In conclusion, an impairment in the renal DA and sodium system can be detected early in IDDM and in individuals with familial hypertension. We speculate that this impairment may contribute to the development of hypertension and microvascular disease in both conditions.
 ...
PMID:The dopaminuric response to high salt diet in insulin-dependent diabetes mellitus and in family history of hypertension. 909 Jun 56

It has been suggested that hereditary risk for hypertension and cardiovascular disease (CVD) as well as intrauterine growth may be involved in the pathogenesis of diabetic nephropathy. In the present study, we investigated the influence of familial and perinatal risk factors on the occurrence of micro- and macroalbuminuria in young IDDM patients. A cohort of 1,150 young patients with > or =5 years' duration of IDDM was screened for microalbuminuria. Data on family history of hypertension, CVD, IDDM, and NIDDM; perinatal factors such as birth weight, gestational age, and duration of breastfeeding; and maternal education, smoking, hypertension, and proteinuria during pregnancy were collected. We identified 75 patients with an albumin excretion rate > or =15 microg/min in more than two overnight urinary samples and compared them in a nested case-control study with three normoalbuminuric control subjects per patient from the same cohort, matched for diabetes duration. Perinatal factors were analyzed in all patients born at term (+/- 2 weeks), 59 of the 75 patients and 155 of the 225 control subjects. In univariate analysis, hypertension in parents (odds ratio [OR] 4.21), CVD in parents and grandparents (OR 1.26), maternal smoking during pregnancy (OR 3.21), and a low level of maternal education (OR 2.33) were significantly associated with the development of micro- and macroalbuminuria. When adjusted for other familial and perinatal factors, current mean blood pressure, HbA1c, smoking, BMI, sex, age, and postpubertal diabetes duration, using logistic regression analyses, only parental hypertension in all patients and maternal smoking during pregnancy and low level of maternal education in full-term patients were independent risk factors. When patients with poor glycemic control were analyzed separately, familial CVD, poor metabolic control, parental hypertension, maternal smoking during pregnancy, and level of maternal education were independent risk factors, with the adjusted OR markedly increased, compared with the matched subgroup with better HbA1c. In conclusion, familial hypertension and CVD, maternal smoking during pregnancy, and low level of maternal education may independently increase the risk for incipient nephropathy in full-term offspring who later develop IDDM. Current poor glycemic control seemed to increase the effect of these risk factors.
Diabetes 1998 Jul
PMID:Familial and perinatal risk factors for micro- and macroalbuminuria in young IDDM patients. 964 37

Maitake mushroom has been reported to favorably influence hypertension and diabetes mellitus. The purpose of this study was to compare the effects of whole Maitake mushroom powder and two extracts designated as ether soluble (ES) and water soluble (WS) on Zucker fatty rats (ZFR), a model of insulin resistance, and on spontaneously hypertensive rats (SHR), a model of genetic hypertension. In the initial study, we followed four groups of eight ZFR and SHR receiving special diets: a baseline diet (BD), BD + whole Maitake mushroom powder (20% w/w), BD + fraction ES (0.10% w/w), and BD + WS (0.22% w/w). Different effects of these dietary regimens on the 2 rat strains were found. At 35 days, only consumption of the ES diet significantly decreased systolic BP (SBP) in SHR (average 197 vs. 176 mm Hg, p < 0.001), while in ZFR only the groups consuming the whole Maitake and WS diets showed significantly decreased SBP (138 vs. 120-125 mm Hg, p < 0.001). A challenge test with losartan (an angiotensin II receptor blocker) indicates that angiotensin II does not play a major role in SBP regulation of ZFR, but does in SHR where consumption of ES relative to other groups significantly lowered activity of this system. In SHR, glucose, cholesterol, circulating insulin and HbA1C were virtually similar among all dietary groups; but whole Maitake (-22%), ES (-120%) and WS (-80%) diets were associated with decreased triglycerides, and the ES diet with lowered serum creatinine (-29%). In ZFR, circulating insulin and HbA1C were significantly decreased in the whole Maitake powder and ES groups, and tended to be lower in the WS group compared to control. In the ensuing studies, we gavaged ZFR once daily with water (control), 44 mg fraction WS, or 44 mg fraction WS plus 100 microg niacin-bound chromium (NBC). Oral gavage of WS clearly lowered SBP and circulating glucose concentrations, more so with the addition of chromium. We conclude that the examined forms of Maitake mushroom have antihypertensive and antidiabetic potential which differ among rat strains. The ES fraction may decrease SBP in SHR via alteration in the renin-angiotensin system.
 ...
PMID:Antihypertensive and metabolic effects of whole Maitake mushroom powder and its fractions in two rat strains. 1223 80

Currently, one of the methods of comprehensive evaluation of patient health status is quality of life assessment. In the management of hypertension, evaluation of quality of life helps in individualization of therapy and improves its efficiency. The aim of the study was to compare the general quality of life between patients with essential hypertension and normal blood pressure values, and to analyse the effect of socio-demographic factors on the quality of life. An open questionnaire was distributed among 1539 patients (775 men and 764 women), aged from 18 to 88 years (x = 51.7 +/- 14.6 years) with essential hypertension detected at least 3 months earlier, referring to treatment for the first time or already treated by general practitioners and the Outpatient Department on Hypertension of the I Cardiac Department. Hypotensive treatment was given to 82.6% of the subjects, whereas 17.4% were untreated. A group of 995 subjects (459 men and 536 women) aged from 18 to 82 years (x = 48.6 +/- 11.2 years) with normal blood pressure values served as controls. All subjects provided data on education employment, body mass index, duration of arterial hypertension, family history, target organ damage, co-morbidity, blood pressure value, heart rate and pharmacological treatment. All subjects filled out a standardised questionnaire--Psychological General Well-Being (PGWB), which evaluated the general quality of life and its sin dimensions: Anxiety, Depressive mood, Subjective Well-being, Self-control, General health and Vitality. Statistical analysis included descriptive statistics, analysis of variance and multiple regression. The general quality of life in patients with essential hypertension was significantly lower than that in age-matched normotensives. The quality of life in women was lower than that in men irrespective of arterial hypertension presence. The quality of life was decreasing with age both in hypertensive and normotensives; however in hypertensive men there was a trend towards improved quality of life above 65 years of age in contrast to age-matched women in whom the quality of life deteriorated. The quality of life in untreated hypertensives was lower than that in age-matched healthy subjects, but until 40 years of age was higher than in treated age-matched hypertensives. The quality of life was related to the level of education, employment and familial history of hypertension. A lower quality of life was observed among hypertensives with coronary heart disease and diabetes. Multiple regression analysis revealed that gender, education, age and familial hypertension were the socio-demographic factors, which independently affected the quality of life among hypertensives. These factors accounted for 32.7% of the observed variance of quality of life. In normotensives subjects the independent factors were gender, age, education and employment--accounting for 65.8% of variance of quality of life.
 ...
PMID:[Quality of life in patients with essential arterial hypertension. Part I: The effect o socio-demographic factors ]. 1293 55

The deletion of thiazide-sensitive Na-Cl cotransporter ( TSC, SLC12A3) causes Gitelman's syndrome characterized by low blood pressure, while deletions of the WNK1 ( PRKWNK1) and WNK4 ( PRKWNK4) genes cause familial hypertension known as pseudohypoaldosteronism type II. Recent studies have revealed that cell surface expression of TSC is regulated by WNK1 and WNK4. We hypothesized that molecular variations in TSC, WNK1, and WNK4 could lead to an increased morbidity of hypertension. We identified 52, 35, and 21 polymorphisms in Japanese hypertensives by sequencing the entire coding regions of TSC, WNK1 and WNK4, respectively. Twenty-one representative polymorphisms were genotyped in 1,818 Japanese individuals (771 subjects with hypertension and 1,047 controls) randomly sampled in Suita city. The results indicated that the systolic blood pressure in men with the CT+TT genotype in WNK4 C14717T was 3.1 mmHg higher than those with the CC genotype ( p=0.042) after adjustment with confounding factors such as age, BMI, hyperlipidemia, diabetes mellitus, antihypertensive drug use, smoking, and drinking. Multivariate logistic regression analysis (with adjustment for the same parameters) in men revealed that the odds ratio for the presence of hypertension of the CT+TT genotype in C14717T to the CC genotype was 1.62 ( p=0.010, 95% confidence interval, 1.12-2.33). Association of TSC and WNK1 with hypertension was not observed. In conclusion, our study suggests the possible involvement of WNK4 in essential hypertension in a Japanese general population.
 ...
PMID:Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population. 1530 83

We have investigated the effects of hypertension associated with diabetes mellitus on polyunsaturated fatty acid biosynthesis. For this purpose, two rat models for these pathologies have been established: a type 1 diabetic hypertensive model obtained by streptozotocin injection to spontaneously hypertensive rat (SHR), followed or not by insulin treatment (experiment 1); a type 2 diabetic hypertensive model by feeding SHR with a fructose enriched diet (experiment 2). Liver gene expression of delta-6 desaturase (D6D), microsomal D6D activities and fatty acid composition of total lipids were estimated. In experiment 1, an increase of linoleic acid (18:2 n-6) level was observed in the streptozotocin group. D6D gene expression appeared depressed in both experimental groups. Insulin did not reverse the streptozotocin effect in SHR, as it does in insulin-dependent diabetic rats. In experiment 2, the results showed a decrease of 18:2 n-6 and of long chain products of desaturation in rats fed on fructose diet. Delta-6 n-3 desaturase activity was significantly increased, whereas gene expression tended to decrease. Feeding fructose induced a significant increase in delta-9 desaturated products, suggesting a stimulation of stearoyl-CoA desaturase. These changes in monounsaturated fatty acids strongly differ from those observed in the streptozotocin experiment, indicating that the effects on lipogenesis of hypertension linked to diabetes differ according to the type of diabetes. Then, these results indicate that the liver steatosis observed during genetic hypertension was reinforced by fructose feeding. All together, the present results showed that hypertension associated to type 1 or type 2 diabetes exacerbated the damage caused by diabetes or hypertension alone on liver lipid metabolism. The metabolic effects induced by fructose being very similar to those found in human NIDDM, SHR fed a fructose-rich diet appears to be an appropriate model for studying the consequences of the combination of hypertension and NIDDM in the metabolic syndrome diseases.
 ...
PMID:Effects of streptozotocin and dietary fructose on delta-6 desaturation in spontaneously hypertensive rat liver. 1558 89

The Cohen-Rosenthal diabetic hypertensive rat is a unique animal model in which genetic hypertension and diabetes developed after crossbreeding of a sensitive substrain of Cohen diabetic rats and spontaneously hypertensive rats (SHR) and feeding them a copper-poor sucrose diet. This study examined the acute effects of endothelin-1 on the systemic and renal hemodynamics in Cohen-Rosenthal diabetic hypertensive rats, Cohen diabetic rats and spontaneously hypertensive rats. Intravenous injection of endothelin- 1 (1.0 nmol/kg) into anesthetized SHR resulted in a significant immediate depressor response in mean arterial pressure [from 165 +/- 3 mmHg to 124 +/- 12 mmHg (P < 0.0001)] followed by a minor hypertensive phase (mean arterial pressure increased to 170 +/- 2 mmHg). Simultaneously, the administration of endothelin-1 caused a significant decrease in renal blood flow from 5.8 +/- 0.9 mL/minute to 3.2 +/- 0.5 mL/minute (P = 0.026). These responses were blunted in Cohen-Rosenthal diabetic hypertensive rats and Cohen diabetic rats. Analysis of intrarenal blood flow by laser-Doppler in Cohen-Rosenthal diabetic hypertensive rats revealed that endothelin-1 injection caused a decrease in cortical blood flow (Delta = -12 +/- 2.9%). However, in contrast to its well known renal medullary vasodilatory effect, endothelin-1 produced a significant decline in the medulla blood flow (Delta = -17.5 +/- 3.4%) (P = 0.0125). These findings suggest that Cohen diabetic rats and Cohen-Rosenthal diabetic hypertensive rats have reduced sensitivity to the vascular and renal action of endothelin-1. Furthermore, in the Cohen-Rosenthal diabetic hypertensive rats the expected endothelin- 1-induced medullary vasodilation was abolished and even reversed into prolonged vasoconstrictor response.
 ...
PMID:Effects of endothelin-1 on systemic and renal hemodynamics in hypertensive-diabetic rats (CRDH), diabetic rats (CDR), and hypertensive rats (SHR). 1583 76

Nitric oxide (NO) is a potent regulator in the cardiovascular system; it is generated by the nitric oxide synthase (NOS) family of proteins. NO produced in endothelial cells plays a crucial role in vascular functions. The aim of this study was to clarify the effect of diabetes on aortic NO synthesis in a model of genetic hypertension and determine whether captopril modulates this effect. Diabetes was induced in ten weeks old spontaneously hypertensive rats (SHR) by streptozotocin injection. The rats were allocated into 3 groups: control group 1, non-diabetic SHR; group 2, diabetic SHR; group 3, diabetic SHR group receiving captopril at 80 mg/kg in drinking water for 4 weeks. Mean blood pressure (MBP) was measured once a week by tail-cuff method. Aortic NO metabolities (nitrite/nitrate) and endothelial NOS (NOS-3) were assayed by Griess reaction and by immunoblotting and immunohistochemistry, respectively. There was a significant decrease in nitrite/nitrate (NOx) in aortas of diabetic SHR compared with controls. The decrease of aortic NOx in diabetic SHR was accompanied by a decrease in NOS-3 expression. Captopril treatment reduced MBP without affecting either NOx level or NOS-3 expression in aortas of diabetic SHR. We conclude that STZ-induced diabetes decreased NO in aortas of SHR that may reflect endothelial cell dysfunction; captopril administration decreased MBP without affecting NO level in aortas of diabetic SHR which suggest that the blood pressure-lowering effects of captopril were independent of NO.
 ...
PMID:Effect of diabetes on aortic nitric oxide synthesis in spontaneously hypertensive rats; does captopril modulate this effect? 1589 Mar 70

The aim of this study was to evaluate the effect of prevention of hypertension on glomerular hypertrophy, renal cell replication and accumulation of glomerular fibronectin in a model of genetic hypertension and experimental diabetes. Four-week-old streptozotocin induced spontaneously hypertensive rats (SHR) were randomized for no treatment, or for treatment with captopril, losartan or triple therapy (hydrochlorothiazide, reserpine and hydralazine) for 20 days. Increase in systolic blood pressure was equally prevented by captopril (118+/-15 mmHg), losartan (111+/-9) and triple therapy (112+/-14, p<0.0001). Glomerular size was higher (p<0.005) in diabetic SHR (27,300+/-2130 microm(2)) compared with non-diabetic SHR (23,800+/-307). The antihypertensive therapy with captopril (23,900+/-175), losartan (23,800+/-120), and triple therapy (23,400+/-210) prevented the glomerular enlargement in diabetic SHR. Glomerular expression of fibronectin was increased in diabetic SHR (7.61+/-1.22 densitometric unit) as compared to the controls (2.27+/-2.15, p<0.0001), and was decreased (p<0.0001 vs diabetic SHR) with captopril (2.49+/-1.42), losartan (1.57+/-1.1) and triple therapy (2.04+/-1.42). The number of replicating glomerular cell significantly decreased in diabetic SHR and it was restored by all three antihypertensive regimes. The glomerular expression of p27(Kip1) was increased in diabetic SHR but it was not modified by antihypertensive treatment. Strict blood pressure control, in diabetic SHR independently of the class of antihypertensive agent, restores glomerular hypertrophy and renal cellular replication, and prevents the increment in glomerular fibronectin.
 ...
PMID:Effects of tight blood pressure control on glomerular hypertrophy in a model of genetic hypertension and experimental diabetes mellitus. 1689 Feb 45


<< Previous 1 2 3 Next >>