Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to evaluate clinical presentation and to determinate classification criteria of type 1 diabetes in the elderly, we carried out a study in 258 diabetic patients more than 60 years old of which 100 used insulin by failure to oral hypoglycemic agents (OHA). The prevalence of ischemic cardiovascular disease was 36%, peripheral vascular disease 34% and stroke 30%. Non-proliferative retinopathy 47%, nephropathy 16% and peripheral neuropathy 37%. Cardiovascular risk factors as obesity (36%), hypertension (33%) and hypercholesterolemia (12%) were evaluated. The average duration of diabetes was 20 years. Post-glucagon C-Peptide, HLA-DR antigens and islet cell antibodies (ICA), were measured in 75 older diabetic patients on treatment of which 24 used insulin, 11 diet and 40 OHA. Older patients on treatment with insulin had longer duration of disease, less obesity, low level basal of C-Peptide and a low response to post glucagon C-Peptide (0.94 +/- 0.5 pmol/ml) compared with patients on diet (1.8 +/- 0.9 pmol/ml) and OHA (1.8 +/- 0.8 pmol/ml). Older diabetics on insulin therapy had a greater frequency of HLA-DR3 (42%) and HLA-DR4 (21%) than other older diabetics. The ICA was negative in most patients. This study shows the high prevalence of macrovascular and microvascular disease in elderly patients with diabetes mellitus and that the most reliable parameter in classifying type 1 (insulin-dependent) diabetes is the measurement of basal and post-glucagon C-Peptide. HLA-DR specific markers can be used with this parameter because their expression is partly shared. This approach appears useful in the older diabetic patients to help classify diabetes and its management.
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PMID:[Diabetes mellitus in the elderly: a study on its clinical presentation, C-peptide reserve, and immunogenetic markers of insulin dependence]. 848 59

The present studies were undertaken to examine if adenylyl cyclase activity and the levels of G-proteins (Gs alpha and Gi alpha) are altered in cardiovascular tissues in hypertension. Adenylyl cyclase activity and its responsiveness to stimulatory and inhibitory hormones as well as the expression of G-proteins (Gs and Gi) were determined at protein and mRNA levels by using specific antibodies and cDNA probes in hearts and aorta from 12 week old spontaneously hypertensive rats (SHR) and their age-matched control Wistar Kyoto (WKY) rats. The stimulatory effects of guanine nucleotides, isoproterenol, glucagon etc. on adenylyl cyclase activity were decreased in SHR rats as compared to the WKY rats, whereas, the inhibitory hormones inhibited enzyme activity to a greater extent in SHR rats as compared to WKY rats. Furthermore, the levels of Gi alpha-2 and Gi alpha-3 proteins and Gi alpha-2 and Gi alpha-3 mRNA as determined by immunoblotting and Northern blotting techniques respectively were higher in SHR as compared to WKY rats. However, the levels of Gs alpha were unaltered in SHR. To further investigate if these alterations are the cause or effect of hypertension, the SHRs at various ages of development of blood pressure (3-5 days, 2, 4 and 8 weeks) and their age-matched WKY were used for G-protein expression and adenylyl cyclase activity. The increased expression of Gi alpha-2 and Gi alpha-3 protein and mRNA levels in hearts and aorta were observed as early as in 2-weeks old SHR as compared to WKY, when the blood pressure was still normal. However, the levels of Gs alpha in SHR were not different from WKY rats. In addition, the altered responsiveness of adenylyl cyclase to hormone stimulation and inhibition was also observed as early as in 2 week old SHR. These results suggest that the increased expression of Gi alpha-2 and Gi alpha-3 and decreased levels of cAMP precedes the development of blood pressure and may be one of the contributing factors in the pathogenesis of hypertension.
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PMID:G-proteins and adenylyl cyclase signalling in hypertension. 873 43

Most obese patients with noninsulin-dependent diabetes mellitus (NIDDM) are initially treated with diet, then with oral hypoglycemic agents, eventually with insulin. However several reports indicate that in these patients insulin therapy has little chance to control glucose metabolism, promotes weight gain and arterial hypertension, and is likely to aggravate insulin resistance. In this randomized, double-blind trial vs. placebo (P) we evaluated in 29 obese NIDDM patients poorly controlled by insulin (daily insulin doses 48.7 +/- 4.0 U/day, HbA1c 10 +/- 0.27%, mean daily blood glucose levels 12.3 +/- 0.3 mmol/L, fasting C-peptide 1.8 +/- 0.2, C-peptide after 1 mg iv glucagon 3.2 +/- 0.3 ng/mL, means +/- SE), the clinical and metabolic effects of benfluorex (B), a lipid-lowering drug able to improve insulin sensitivity. After a 2-3 week run-in period (1 tablet P at dinner and diet 800 cal/day to lose 5% of the initial body weight (BWi), patients received a 1000 kcal/day diet and were randomized to B, 150 mg/ tablet, or P (3 tablets/day); the time limit was set at a 10% decrease of BWi or at 90 days. At the end of run-in there was a significant reduction of BWi (P < 0.001), fasting (P = 0.002) and mean daily blood glucose levels (P < 0.001), triglycerides (P = 0.02), cholesterol (P < 0.001) and daily insulin doses (P < 0.001). At the end of the double-blind trial, weight-loss was greater (P < 0.05), faster (P = 0.018), and more frequent (P < 0.05) with B than with P, and systolic blood pressure (P < 0.05) decreased only with B. Considering only patients with a 10% decrease of BWi (B = 15, P = 10), HbA1c (P < 0.001) decreased only with B, while fasting insulin levels decreased with both B (P < 0.01) and with P (P < 0.05). Insulin sensitivity was evaluated by means of a double infusion test (LDIGIT, insulin 25 mU/Kg/h plus glucose 4 mg/kg/min, lasting 150 min) at the end of run-in and at the end of the double-blind trial; at the end of the double-blind trial steady state blood glucose (SSBG, P < 0.05), free fatty acids (FFA, P < 0.05) and blood beta-hydroxybutyrate (P < 0.05) decreased only with B, while blood glycerol decreased both with both P (P < 0.05) and B (P < 0.06). At the end of the double-blind trial, C-peptide release was unchanged with either P or B. In conclusion, benfluorex potentiates the effects of hypocaloric diet on weight loss and on glycemic control in obese NIDDM patients treated with insulin, and this effect seems to be the result of an improved insulin sensitivity.
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PMID:Benfluorex in obese noninsulin dependent diabetes mellitus patients poorly controlled by insulin: a double blind study versus placebo. 885 30

Endocrine disorders associated with diabetes mellitus are described. When blood glucose control deteriorates, observed endocrine abnormalities are as follows. 1) Blood GH levels increase. This elevation is small but enough to disturb insulin secretion and glucose metabolism. Plama insulin-like growth factor-1 levels decrease in spite of their strong relation with diabetic retinopathy. 2) Blood thyroid hormones show the similarity with low T3 syndrome. 3) Hyporeninemic hypoaldosteronism occurs especially with patients who have hypertension or moderate diabetic complications. 4) Plasma pancreatic glucagon levels are elevated. Amino acids induce hypersecretion but hypoglycemia fails to response normally. Glucose administration shows impaired inhibition or paradoxical hypersecretion. 5) Other plasma levels of pancreatic hormones such as gastrin, secretin, motilin and somatostatin are usually elevated.
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PMID:[Endocrine disorders associated with impaired glucose tolerance]. 891 25

1. A missense mutation leading to reduced ligand affinity in the glucagon receptor (GCG-R) has been found recently to be five-fold more common in essential hypertensives than normotensives. The present paper provides additional information on patients that harbour this variant and proposes a possible mechanism by which this may lead to hypertension. 2. The seven hypertensives with the mutation were all female, had a later age of onset of the disease and a slightly higher body mass index. 3. Glucagon is involved in the regulation of fluid and electrolyte excretion. Mutant GCG-R results in reduced ligand affinity and cAMP response which, in the kidney, would reduce the normal natriuretic effect of glucagon. This could lead to enhanced fluid reabsorption, expansion of extracellular fluid volume and hypertension via long-term autoregulation of blood pressure.
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PMID:Hypothesis: glucagon receptor glycine to serine missense mutation contributes to one in 20 cases of essential hypertension. 897 55

Noninsulin-dependent diabetes mellitus is a genetically determined form of diabetes, due to impaired insulin secretion by the B-cells as well as to insulin resistance of the peripheral tissues. According to the glucose toxicity theory hyperglycemia and hyperinsulinemia exist in a vicious circle. Therefore, it is a major therapeutical aim to put the B-cell to rest and improve insulin sensitivity by a strict control of fasting blood glucose and of postprandial hyperglycemia. Furthermore, associated abnormalities within the metabolic syndrome, such as hypertension, dyslipoproteinemia and hemostatic disorders should be corrected to avoid vessel complications. Therefore, it should be started with basic measures as body weight reduction, carbohydrate-rich and fat-poor diet and exercise. If these measures fail to achieve acceptable glycemic control, antihyperglycemic drugs (acarbose, metformin) are indicated, eventually in a combination with small doses of short-acting sulfonylureas. Further impairment of insulin secretion is the indication for sulfonylurea and/or insulin application. HbA1c of 7 to 7.5% should be the goal of antidiabetic therapy, also for patients in advanced age. The main criterion for the choice of antidiabetics is the present insulin secretion capacity. Simple indicators in this respect are changes of body weight, plasma triglycerides and C-Peptide after i.v. glucagon stimulation. Application of insulin in combination with other antidiabetics or in the form of intensified insulin therapy should not be too much postponed.
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PMID:[Rational therapy of Type II diabetes]. 903 69

A 46-year-old man was found to have numerous cerebellar hemangioblastomas on magnetic resonance imaging (MRI). He denied any symptoms and had no history of hypertension, but his family history was remarkable for a father who died of renal cell carcinoma. Computed tomography (CT) of the abdomen revealed bilateral adrenal pheochromocytomas with significant enhancement in the regions where 131I-metaiodobenzylguanidine (MIBG) had noticeably accumulated. Endocrinological examinations demonstrated high plasma and urine catecholamine concentrations which were very responsive to metoclopramide and glucagon loading tests, without a significant change in blood pressure. After resection of bilateral pheochromocytomas, he underwent an operation for the cerebellar tumors. Since pheochromocytomas associated with Lindau or von Hippel-Lindau (VHL) disease have a tendency to multiple occurrence in normotensive patients, we suggest that patients with a family history involving VHL lesions should undergo cranial MRI, abdominal CT, MIBG scintigraphy and endocrinological examinations.
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PMID:Normotensive bilateral pheochromocytoma with Lindau disease: case report. 907 13

To investigate the frequency of pheochromocytoma in patients with incidentally discovered adrenal masses (incidentalomas) and to evaluate the sensitivity, specificity and diagnostic accuracy of the Glucagon test in comparison with resting plasma catecholamines, 89 patients with adrenal incidentalomas (age range 23-80 yr; 41 males and 48 females) were studied. Fifty-seven patients were normotensive (SBP 130+/-1.8 mmHg; DBP 80+/-0.7 mmHg, mean+/-SE) and 32 had stable hypertension (SBP 155+/-3.3 mmHg, DBP 93+/-1.4 mmHg): no patient complained of typical signs or symptoms of pheochromocytoma. Resting plasma samples for noradrenaline and adrenaline determination and, at appropriate intervals, the Glucagon test (1 mg i.v.), were performed in all subjects. Diagnosis of pheochromocytoma was made on the basis of humoral evaluations and/or surgical intervention in 6 patients (6.7%), of whom 3 hypertensives and 3 normotensives. Resting plasma catecholamines revealed 5 out of 6 patients with pheochromocytoma: in 3 cases both catecholamines were above the normal range, in 1 only adrenaline was elevated and in 1 case only noradrenaline. Similarily, the glucagon test identified 5/6 pheochromocytomas: in 3 patients the response was abnormal for both catecholamines, in 1 only for adrenaline and in 1 case only for noradrenaline. The sensitivity, specificity, and diagnostic accuracy of resting plasma catecholamines and of the glucagon test were comparable: 83.3%, 96.3%, and 95.5%, respectively. In conclusion, the frequency of pheochromocytoma in adrenal incidentalomas is not negligible, and since the diagnostic accuracy of the Glucagon test is the same of that of resting plasma catecholamines, the former does not appear to offer additional advantages in the diagnosis of incidentally discovered pheochromocytomas.
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PMID:Frequency of pheochromocytoma in adrenal incidentalomas and utility of the glucagon test for the diagnosis. 912 85

We have recently shown an enhanced expression of inhibitory guanine nucleotide regulatory proteins Gi alpha-2 and Gi alpha-3 and their respective mRNA in hearts from DOCA-salt hypertensive rats. However, it is not known whether these changes are due to the expressed hypertrophy or hypertension. The present studies were therefore undertaken to investigate this possibility. Hypertension in Sprague-Dawley rats was induced by the oral administration of the arginine analog N(omega)-nitro-L-arginine methyl ester (L-NAME) in their drinking tap water for a period of 4 weeks. The control rats were given plain tap water only. L-NAME-treated rats showed an enhanced blood pressure (190 +/- 9.23 mm Hg; n = 20) compared to control rats (121 +/- 6.3 mm Hg; n = 20). However, heart to body weight ratio was not different in the two groups. Guanosine 5'-o-(3-thiotriphosphate) (GTPgammaS) stimulated adenylyl cyclase activity in heart membranes from both groups, but the extent of stimulation was significantly decreased in L-NAME-treated rats. Similarly, stimulations exerted by isoproterenol, glucagon, NaF, and forskolin on adenylyl cyclase were also diminished in L-NAME-treated rats. On the other hand, the inhibitory effect of low concentrations of GTPgammaS on forskolin-stimulated enzyme activity was significantly enhanced. The extent of oxotremorine-mediated inhibition of adenylyl cyclase was unaltered in both control and L-NAME-induced hypertensive rats. The levels of Gi alpha-2 and Gi alpha-3, but not of stimulatory guanine nucleotide regulatory protein Gs alpha, as determined by immunoblotting, were significantly augmented in L-NAME-treated rats. Northern blot studies revealed a significant increase in Gi alpha-2 and Gi alpha-3 mRNA with no changes in Gs alpha mRNA. These results suggest that the altered expression of Gi alpha proteins and adenylyl cyclase activity in L-NAME-treated rats may be attributed to hypertension and not to hypertrophy.
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PMID:Nitric oxide synthase inhibition by N(omega)-nitro-L-arginine methyl ester modulates G-protein expression and adenylyl cyclase activity in rat heart. 912 16

In the present studies we have investigated if the increased expression of Gi alpha proteins reported earlier in heart and aorta from SHR (spontaneously hypertensive rats) is the cause or effect of hypertension. The SHRs at various ages of the development of blood pressure (3-5 days, 2 weeks, 4 weeks and 8 weeks) and their age-matched WKY were used for these studies. The expression of Gi alpha-2 and Gi alpha-3 (inhibitory guanine nucleotide regulatory protein and Gs alpha (stimulatory guanine nucleotide regulatory protein) at protein and mRNA level was determined by immunoblotting and Northern blotting technique using specific antibodies and cDNA probes. The SHR at early ages up to 2 weeks did not show any increase in blood pressure, however it started to go up from 4 weeks. The levels of Gi alpha 2 and Gi alpha 3 at protein and mRNA in heart from SHR were not different in 3-5 days old SHR as compared to WKY (Wistar-Kyoto rats), however, the expression of Gi alpha-2 and Gi alpha-3 protein and mRNA was significantly increased in 2 weeks and older SHR. The mRNA level of the catalytic subunit type V enzyme was significantly decreased in SHR 2 weeks and later ages as compared to their age-matched WKY. On the other hand, the expression of Gs alpha was not different in SHR as compared to WKY at all the ages studied. In addition, the oxotremorine and C-ANF4-23 (a ring deleted analog of atrial natriuretic factor) mediated inhibitions of adenylyl cyclase in hearts and aorta were also significantly enhanced in 2 weeks and older SHRs as compared to WKY rats, whereas, at younger age of SHR (3-5 days old), no change in the percent inhibition of adenylyl cyclase by C-ANF4-23 was observed and oxotremorine was unable to inhibit adenylyl cyclase activity. Furthermore, the basal enzyme activity and the stimulatory responses of isoproterenol, NECA (N-ethylcarboxamideadenosine), glucagon and forskolin on adenylyl cyclase were significantly decreased at all ages of SHR as compared to WKY. These results suggest that the increased expression of genes for Gi alpha-2 and Gi alpha-3, decreased expression of type V enzyme mRNA and decreased cAMP levels precedes the development of blood pressure and may participate in the pathogenesis of hypertension.
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PMID:Enhanced expression of Gi-protein precedes the development of blood pressure in spontaneously hypertensive rats. 915 62


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