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

We examined the influence of experimental diabetes on the proliferation of cultured vascular smooth muscle cells (VSMCs) in presence of a nitric oxide (NO)-generating agent, sodium nitroprusside (SNP), and 8-bromo-cGMP. VSMC cultures were prepared from aortas of control and streptozotocin-diabetic rats. SNP induced a time- and dose-dependent inhibition of control and diabetic VSMC proliferation, consistent with the data on [3H]thymidine incorporation, cell counts, and index of culture mass. However, the responses to SNP were significantly enhanced in VSMCs from diabetic rats. SNP induced an increased dose-dependent accumulation of intracellular cGMP in diabetic VSMCs. In contrast, growth-inhibitory responses to 8-bromo-cGMP were not significantly different between the two VSMC models. Moreover, basal cGMP content in VSMCs was lower in diabetic rats than in controls, a result that can explain the enhanced proliferation observed in VSMCs from diabetic rats. These results suggest an enhanced antiproliferative effect of NO in VSMCs from diabetic rats through increased cGMP production. Therefore, experimental diabetes may impair and up-regulate soluble guanylate cyclase activity in VSMCs.
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PMID:Enhanced antiproliferative effect of nitric oxide in cultured smooth muscle cells from diabetic rats. 865 48

In insulin-dependent diabetes mellitus (IDDM) elevated exchangeable sodium (Na) levels are found even in the absence of hypertension, but it is not known whether this is associated with increased sensitivity of blood pressure to sodium level. To clarify this issue we compared 30 patients with IDDM (19 without and 11 with microalbuminuria, i.e. more than 30 mg albumin/day) and 30 control subjects matched for age, gender and body mass index. The subjects were studied on the 4th day of a low-salt diet (20 mmol/day) under in-patient conditions and were subsequently changed to the same diet with a high-salt supplement, yielding a total daily intake of 220 mmol Na/day. Circadian blood pressure, plasma renin activity (PRA), plasma atrial natriuretic factor (p-ANF), plasma cyclic guanosine 5'-phosphate (p-cGMP) and urinary albumin were measured. The proportion of salt-sensitive subjects, i.e. showing increment of mean arterial pressure > or = 3 mmHg on high-salt diet, was 43% in diabetic patients (50% of diabetic patients with and 37% without microalbuminuria) and 17% in control subjects (p < 0.05). Lying and standing PRA levels on low- or high-salt diet were significantly lower in diabetic patients than in control subjects. Salt-sensitive diabetic patients had significantly higher lying ANF on high-salt (38.7 +/- 4.2 pmol/l vs 20.1 +/- 2.3 pmol/l, p < 0.005) than on low-salt diet. The results suggest that (i) the prevalence of sodium sensitivity is high in IDDM (ii) sodium sensitivity is found even in the absence of nephropathy as indicated by albuminuria.
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PMID:Increased prevalence of salt sensitivity of blood pressure in IDDM with and without microalbuminuria. 878 18

We examined the influence of streptozotocin-induced diabetes on the growth of cultured rat aortic smooth muscle cells in the presence of interleukin-1 beta. Interleukin-1 beta induced a dose-dependent biphasic effect on proliferation of diabetic and control smooth muscle cells, consistent with the data on [3H]thymidine incorporation and cell counts. However, the major effect of interleukin-1 beta was to stimulate growth of diabetic cells and inhibit growth of control cells. Furthermore, interleukin-1 beta induced a dose-dependent increase in nitric oxide (NO) release and in intracellular cyclic GMP accumulation: nitrite release was similar in both smooth muscle cell models but cyclic GMP accumulation was greater in diabetic cells than in controls. These results suggest that the inhibitory loop involving NO is not effective enough to completely counterbalance the stimulatory effects of interleukin-1 beta on diabetic cells. Therefore, experimental diabetes may modify the interleukin-1 beta-regulated smooth muscle cell growth.
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PMID:Regulation of growth of cultured smooth muscle cells from diabetic rats by interleukin-1 beta: role of nitric oxide. 888 40

To elucidate the underlying mechanisms of platelet dysfunction in diabetes mellitus, we examined the activity of soluble guanylate cyclase (sGC), a key enzyme in the nitric oxide (NO)-related signalling pathway, in platelets from NIDDM (non-insulin dependent diabetes mellitus) patients. The sGC activity was determined by measuring the amount of cyclic GMP produced in platelet cytosol. In the first study, we investigated the platelet sGC activity in untreated NIDDM patients without diabetic complications. In the male NIDDM patients, sodium nitroprusside (SNP) caused a significantly lower sGC response than that in age-matched control male subjects, while the enzyme activity of female diabetics did not differ from that in the controls. Secondly, we investigated effects of diabetic-associated factors on the enzyme activity in the male NIDDM patients. There was no difference in the SNP-stimulated sGC activity in platelets from male diabetics between with and without retinopathy. In the male diabetic patients with retinopathy, however, the platelet sGC activity was slightly increased by treatment with insulin. Interestingly, the changes in enzyme activity did not correlate with plasma glycosylated hemoglobin A1c levels in diabetic patients. The impairment of the NO-related signalling pathway may contribute to the platelet dysfunction observed in patients with diabetes mellitus.
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PMID:Nitric oxide-dependent soluble guanylate cyclase activity is decreased in platelets from male NIDDM patients. 889 Sep 25

We have cloned the coding region of a human gene, whose predicted amino acid sequence shows 88% homology and higher correspondence in functional domains to the rat cGMP inhibited phosphodiesterase gene (PDE3A). In concordance with the expression data of the rat PDE3A gene, a 5.3-kb transcript of the human cGMP-inhibited phosphodiesterase gene is shown in Northern blot analysis to be highly expressed in adipose tissue. In addition, weaker expression is seen in pancreas, skeletal muscle, liver, placenta, and heart. cDNA clones from the homologue mouse gene were isolated and sequenced spanning a highly conserved region coding for a C-terminal located catalytic core region of this enzyme family. Using a genomic cosmid clone of human PDE3A for fluorescence in situ hybridization, the gene was mapped to chromosomal region 11p15 and regionally sublocalized by PCR on a human-hamster somatic hybrid-cell mapping panel to 11p15.1-p2. Based on comparative linkage data in mouse and rat this chromosomal location is suggested to contain genes involved in complex diseases like obesity and diabetes mellitus type II. Therefore, a possible involvement of the human PDE3A gene in these polygenic traits is discussed, taking into account the prominent role of the rat PDE3A gene product in the antilipolytic action of insulin in adipocytes.
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PMID:Molecular cloning and chromosomal assignment of the human homologue of the rat cGMP-inhibited phosphodiesterase 1 (PDE3A)--a gene involved in fat metabolism located at 11p 15.1. 892 98

Leptin, a recently identified hormone, is believed to reduce appetite and maintain body weight. The mRNA of leptin is expressed only in mature adipose cells. To clarify the regulation of leptin gene expression in adipocytes, 3T3-L1 adipocytes were treated for 16 h with various agents known to modulate lipid metabolism, and then the leptin mRNA was measured by the reverse transcription-polymerase chain reaction method. Interestingly, both norepinephrine and isoproterenol reduced the level of leptin mRNA to about 20% of that found in untreated control cells in a dose-dependent fashion. The maximum reduction occurred at 100 nmol/l of either norepinephrine or isoproterenol, and the half-maximal effect was observed at approximately 3 nmol/l norepinephrine and approximately 1 nmol/l isoproterenol. Propranolol reversed about 50% of the reduction by either norepinephrine or isoproterenol. In contrast, phentolamine did not inhibit the reduction by either norepinephrine or isoproterenol. Moreover, both cholera toxin and dibutyryl cAMP decreased the level of leptin mRNA to about 10% of that in control cells in a dose-dependent fashion. The maximum effect was elicited at 100 ng/ml cholera toxin and 100 micromol/l dibutyryl cAMP. The concentration producing the half-maximal effect was approximately 1 ng/ml cholera toxin and approximately 50 micromol/l dibutyryl cAMP. Dibutyryl cGMP, however, did not affect leptin gene expression. These results suggest that a signaling pathway that results in the activation of protein kinase A regulates leptin gene expression in 3T3-L1 adipocytes.
Diabetes 1996 Dec
PMID:Reduced expression of the leptin gene (ob) by catecholamine through a G(S) protein-coupled pathway in 3T3-L1 adipocytes. 892 60

Hypertension is commonly associated with diabetes mellitus. The aim of the present study was to explore the pathophysiological significance of the natriuretic peptide (NP) system in hypertension associated with genetically obese/hyperglycemic Wistar fatty rats. The messenger RNA (mRNA) levels of the two biologically active NP receptors, NP-A receptor [more specific for atrial natriuretic peptide (ANP)] and NP-B receptor [more specific for C-type natriuretic peptide (CNP)], and CNP mRNA levels were determined in the aorta and kidney by ribonuclease protection assay. Plasma ANP levels were determined by RIA. Both NP-A and NP-B receptor mRNA levels in the aortae of Wistar fatty rats were double those in Wistar lean rats. Plasma ANP levels and CNP mRNA levels in the aorta of Wistar fatty rats were also significantly higher than those in Wistar lean rats. In contrast, there was no significant difference in renal levels of the mRNA for both NP receptors and CNP between the two strains. Administration of a NP-A and -B receptor antagonist, HS-142-1, to Wistar fatty rats resulted in a significant increase in systolic blood pressure and a larger decrease in plasma cGMP level than that in Wistar lean rats, with no difference in the extents of decrease in urine volume and urinary sodium excretion between the two strains. These results suggest that both the ANP/NP-A system and the CNP/NP-B system in vessels are up-regulated at the level of gene expression and may, thus, play an important role in counteracting the hypertension associated with diabetes mellitus.
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PMID:Vascular action of circulating and local natriuretic peptide systems is potentiated in obese/hyperglycemic and hypertensive rats. 894 Mar 83

It is well established that estrogens and progestogens are able to influence the vasotonus in postmenopausal women. The present study was undertaken to find out if the NO/cGMP-system is involved in this hormone action. Urinary cGMP excretion which can reflect intracellular cGMP production elicited by NO (EDRF) was investigated in 20 postmenopausal women. In an open cross-over study design norethisterone acetate was administered orally for 8 days, estradiol valerate orally for 9 days and a combination of both substances for 12 days. After all three treatment phases urinary cGMP expressed as percentage of the pretreatment value was increased at a statistically significant level. Due to high individual variations no significant differences could be found among the values after the three treatment phases. It was concluded that the NO/cGMP-system may play a role in maintaining vasotonus in postmenopausal women under hormone replacement therapy.
Exp Clin Endocrinol Diabetes 1996
PMID:Urinary cGMP excretion after hormone replacement therapy in postmenopausal women. 895 75

Tissue-type plasminogen activator (tPA) is an endothelium-derived vasoactive substance which is released to the blood stream by exercise, blood occlusion, and desmopressin (DDAVP). The increased capacity of the plasma tPA level raised by these factors is thought to reflect in vivo endothelial function. On the other hand, endothelial dysfunction has been reported in patients with hypercholesteremia as well as in those with diabetes mellitus. Therefore, diabetic patients with hypercholesteremia were administered 5 mg of simvastatin daily for one month and plasma tPA responses evoked by DDAVP were examined before and after treatment for hypercholesteremia. While the treatment of simvastatin for one month significantly reduced serum cholesterol levels from 257 +/- 12 mg to 206 +/- 10 mg (no change in HbA1c was observed during the study), plasma tPA levels and % delta vWF (von Willebrand factor) following DDAVP infusion significantly increased from 11.4 +/- 1.2 ng/ml to 13.4 +/- 1.4 ng/ml and from 69.3 +/- 23.4% to 126.5 +/- 47.4%, respectively. However, neither increase in plasma levels of guanosine 3', 5'-cyclic monophosphate (cGMP) nor change in the depressive response of blood pressure was observed following DDAVP infusion after the treatment of simvastatin. In addition, no change in urinary albumin excretion rate was observed with the treatment of hypercholesteremia. Therefore, it was suggested that improvement in hypercholesteremia may ameliorate vascular endothelial dysfunction in diabetic patients with hypercholesteremia and that hypercholesteremia may enhance endothelial dysfunction in these patients.
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PMID:[Effect of hypercholesteremia on vascular endothelial function and albumin excretion rate in patients with diabetes mellitus]. 895 5

In the present study, we evaluated whether acute dietary supplementation with L-arginine in vivo could reverse the defective endothelium-dependent relaxation in diabetic blood vessels assessed ex vivo. At 8 weeks of diabetes, streptozotocin-induced diabetic rats were given 1.25% L-arginine in drinking water 3 days prior to isolation of aortic rings for evaluation ex vivo. Plasma arginine concentration was reduced by diabetes but restored to normal in diabetic rats receiving dietary L-arginine. In norepinephrine-contracted rings, relaxation to acetylcholine but not to nitroglycerin was reduced by diabetes. Dietary treatment with L-arginine restored relaxation to acetylcholine without altering relaxation to nitroglycerin and restored the defect in acetylcholine-stimulated cGMP generation. These data suggest that the substrate for nitric oxide synthesis by the endothelium is likely to be limited in diabetes but can be overcome by dietary supplementation with L-arginine.
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PMID:Short-term oral administration of L-arginine reverses defective endothelium-dependent relaxation and cGMP generation in diabetes. 899 16


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