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

Dilution of thrombocyte-rich blood plasma (down to 2.5 x 10(8) thrombocytes/ml) enabled to avoid an irreversible phase of the ADP-induced thrombocyte aggregation; the reversible phase of aggregation was followed by deaggregation. The reversible aggregation of thrombocytes was studied in healthy persons and patients with diabetes mellitus within wide ranges of ADP concentrations (including 10 microM) using the diluted blood plasma. Thrombocytes of the patients with diabetes mellitus of the I and II types were found to be 1.6- and 2.33-fold more sensitive to the ADP aggregating effect as compared with thrombocytes of healthy persons. The elevated rate of thrombocytes aggregation in diabetes mellitus appears to be related to early decrease in activity of thrombocyte guanylate cyclase and to its ability to be activated.
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PMID:[ADP-induced aggregation of human platelets in diabetes mellitus]. 223 25

1. Acetylcholine (ACh)-induced relaxation of aortic strips with endothelium and production of cyclic GMP between streptozotocin-induced diabetic and age-matched control rats were compared. 2. The concentration-response curve for ACh-induced relaxation was shifted to the right in diabetic rats. IC50 values for ACh were 4.57 +/- 0.67 x 10(-8) M and 1.00 +/- 0.87 x 10(-7) M in aortic strips from age-matched control and diabetic rats, respectively (n = 6, P less than 0.05). 3. Relaxations produced by atrial natriuretic peptide (ANP) in diabetic aortae were similar to those in age-matched vessels. 4. Relaxations produced by sodium nitroprusside (SNP) in diabetic aortae were similar to those in age-matched vessels. 5. Basal levels of cyclic GMP and ACh-induced production of cyclic GMP were significantly decreased in diabetic rats. 6. These results suggest that functional changes in endothelium but not in guanylate cyclase activity in the aorta may occur in diabetes, and thus, spontaneous and ACh-induced formation of cyclic GMP may be decreased. This decrease in production of cyclic GMP may be responsible for the decreased response of the aorta to the relaxant effect of ACh.
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PMID:Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in aorta from streptozotocin-induced diabetic rats. 254 80

Clear differences in properties of platelet guanylate cyclase from healthy donors and patients with diabetes mellitus were identified; departure from the norm was more pronounced in the case of the II-type of this disease, than the I-type. We have registered the decrease in the Mg-activity (basal) of guanylate cyclase by 30 and 50 per cent, Mn-activity--by 20 and 30 per cent, the state of guanylate cyclase activation by 0.1 mM sodium nitroprusside to 2 and 3-fold in patients with I and II-type of diabetes mellitus, consequently. The possible causative factors of these disturbances are discussed. It is suggested that the decrease in guanylate cyclase activation by nitroprusside is due to the enzyme heme-deficiency rising with the diabetes mellitus.
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PMID:[Human thrombocyte guanylate cyclase in diabetes mellitus]. 256 38

Eight weeks following streptozotocin-induced diabetes mellitus in rats, the sensitivity of adenylate cyclase to dopamine (DA) and norepinephrine (NE) was reduced in homogenates of retina. Furthermore, the activation of adenylate cyclase in cerebral microvessels (capillaries) by NE, 5'-guanylyl imidodiphosphate (alone or with NE) and forskolin was reduced in diabetic rats versus appropriate controls. In diabetic rats enzyme sensitivity to only NE was attenuated in homogenates of cerebral cortex and cortical piaarachnoid. No differences between controls and diabetics were noted with respect to guanylate cyclase or cyclic AMP phosphodiesterases. The damage observed in retina and microvessels may play an important pathogenic role in diabetes-induced blindness and stroke.
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PMID:Streptozotocin-induced diabetes produces alterations in adenylate cyclase in rat cerebrum, cerebral microvessels and retina. 613 68

Adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) mediate penile erection. We have previously established that adenylate and guanylate cyclase activity is elevated in the diabetic rat penis and aorta. This study investigates the action of papaverine and vasoactive intestinal polypeptide (VIP) on these cyclases. The aortae and penes of Sprague Dawley rats (n = 7) were stimulated with VIP and papaverine. Diabetes mellitus (DM) was induced in Sprague Dawley rats (n = 7) with streptozotocin and the penile and aortic tissues were treated with VIP. The penes, aortae and carotid arteries of New Zealand White rabbits were similarly processed. cAMP and cGMP generation was measured by radioimmunoassay. In all tissues: VIP stimulated cAMP synthesis; VIP did not increase cGMP levels; papaverine was without effect on either cAMP or cGMP synthesis. VIP-stimulated cAMP was significantly enhanced in the diabetic rat penis and aorta; there was also a significant elevation in the basal levels of cGMP in these tissues. These data: (1) consolidate that cAMP is a mediator of penile erection, (2) indicate that papaverine and VIP elicit erection by different mechanisms, (3) suggest that an enhanced penile capacity to generate cAMP in DM may constitute an adaptive response to counteract the previously reported reduction in VIP content and VIP receptors, and (4) indicate that the penile and vascular tissues of the rabbit respond in a similar manner to VIP and papaverine.
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PMID:Effects of papaverine and vasointestinal polypeptide on penile and vascular cAMP and cGMP in control and diabetic animals: an in vitro study. 749 46

Nitric oxide (NO)-dependent cyclic guanosine monophosphate (cGMP) generation was examined in glomeruli isolated from 1-2-wk and 2-mo streptozotocin diabetic (D) and control (C) rats. After 1-2 wk of diabetes, ex vivo basal cGMP generation and cGMP responses to carbamylcholine (CCh) were significantly suppressed in glomeruli from D compared with those from C, whereas cGMP responses to the calcium ionophore A23187 and nitroprusside (NP) did not differ in glomeruli from D vs. those from C. After 2 mo, glomeruli from D did not respond to CCh, and responses to A23187 and NP were suppressed compared with those from C. Differences in basal, CCh, and A23187-responsive cGMP between D and C were abolished by the NO synthetase inhibitor NG-monomethyl-L-arginine. Soluble glomerular guanylate cyclase prepared from either D or C responded indistinguishably to NP, suggesting a role for NO quenching in the suppression of cGMP in intact glomeruli from D. Compared with those from C, glomeruli isolated from D demonstrated increased generation of thromboxane A2 (TXA2) and activation of protein kinase C (PKC). Both the TXA2/endoperoxide receptor antagonist Bay U3405 and inhibitors of PKC activity restored a cGMP response to CCh in glomeruli from D. Conversely, in glomeruli from C, the TXA2/endoperoxide analogue U46619 activated PKC and suppressed the cGMP response to CCh. Both of those actions were blocked by inhibitors of PKC. The results indicate a progressive impairment of NO-dependent cGMP generation in glomeruli from D which may be mediated in part by TXA2 and activation of PKC. This impairment may participate in glomerular injury in diabetes.
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PMID:Impaired nitric oxide-dependent cyclic guanosine monophosphate generation in glomeruli from diabetic rats. Evidence for protein kinase C-mediated suppression of the cholinergic response. 750 12

To investigate whether insulin reduces platelet aggregability through a modulation of the guanosine-3',5'-cyclic monophosphate (cGMP) concentrations, we determined by a radioimmunoassay the cGMP values in the platelet-rich plasma (PRP) obtained from 17 healthy volunteers and incubated for 3 min with different concentrations of human recombinant insulin (0, 240, 480, 720, 960, and 1,920 pM). Insulin induced a dose-dependent cGMP increase, from 18.5 +/- 3.3 to 42.0 +/- 6.4 pmol/10(9) platelets (P = 0.0001). This increase was completely blunted when PRP was preincubated for 20 min with the tyrosine kinase inhibitor genistein (10 microM) or with the guanylate cyclase inhibitor methylene blue (10 microM), but the increase remained highly significant (P = 0.003 and 0.009) when PRP was preincubated for 20 min with the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX, 500 microM) or with the nitric oxide synthase inhibitor NG-mono-methyl-L-arginine (L-NMMA, 30 microM). Finally, the insulin-induced decrease of platelet aggregability to collagen and ADP was completely blunted when PRP was preincubated with 10 microM of the guanylate cyclase inhibitor methylene blue. This study demonstrates that the platelet anti-aggregatory effect exerted by insulin is attributable to the insulin-induced increase of cGMP that is due to a direct receptor-mediated platelet guanylate cyclase activation.
Diabetes 1994 Aug
PMID:Insulin increases guanosine-3',5'-cyclic monophosphate in human platelets. A mechanism involved in the insulin anti-aggregating effect. 751 80

Progression of diabetic nephropathy is now associated with intrarenal hemodynamic disorders (renal hyperperfusion, hyperfiltration, intraglomerular hypertension). The cause of these disorders is unclear. It is supposed that the relaxation factor which is produced by the vascular endothelium (endothelial relaxation factor-ERF) and an endogenous nitrogen oxide (NO) can cause the above intrarenal hemodynamic alterations in diabetes mellitus. The production of ERF/NO in 35 patients with insulin-dependent diabetes mellitus who had varying severities of diabetic nephropathies were examined. These included the following groups: 1) patients without diabetic nephropathy (n = 9); 2) those with incipient diabetes mellitus (n = 12), 3) those with severe diabetes mellitus (n = 14). From groups 1 and 2, 5 patients with hyperfiltration were identified, their glomerular filtration rate were more than 140 ml/ml. The ability of the cells to produce ERF/NO was indirectly estimated, by determining the levels of human platelet guanylate cyclase in the presence of L-arginine, a NO precursor, the accumulation of cGMP in the cells and plasma. When L-arginine was present, the activity of guanylate cyclase was virtually unchanged in Group 1, but it was substantially increased in Groups 2 and 3, by reaching its peak in patients with hyperfiltration (Group 4). The platelet and plasma levels of cGMP corresponded to the enhancement of guanylate cyclase activity in the presence of L-arginine and increased as diabetic nephropathy progressed. Thus, it is suggested that there is ERF/NO hyperproduction in patients at a high risk for diabetic nephropathy (those having hyperfiltration). ERF/NO is likely to promote the dilation of glomerular arterioles, which results in the development of hyperfiltration and intraglomerular hypertension, causing diabetic nephropathy progression.
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PMID:[Endothelial relaxation factor in the development of diabetic nephropathy]. 762 82

Recent investigations have suggested that the vascular endothelium is an active participant in the regulation of arterial tone and blood flow. In a state of health, the endothelium contributes to hemodynamic equilibrium; however, it rapidly becomes dysfunctional in hypercholesterolemia and diabetes mellitus or with exposure to the stress of hypertension or long-term smoking. Among the deficits observed during endothelial dysfunction is a reduction in the synthesis and release or an excessive degradation of EDRF. This potent vasorelaxant is derived from the amino acid L-arginine and has been characterized as NO or a closely related substance. EDRF relaxes vascular smooth muscle by activating guanylate cyclase. A deficiency in the activity of EDRF may be the mechanism of diminished coronary vasodilation in patients with ischemic heart disease. Organic nitrates, which are metabolized to NO or S-nitrosothiol at the cellular level, are often used in the management of myocardial ischemia; they also induce vasodilation by activating guanylate cyclase. The similarities between organic nitrates and endogenous EDRF and their interactions are discussed in this review.
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PMID:Endothelium, coronary vasodilation, and organic nitrates. 783 12

The intracellular content of cyclic GMP (cGMP) is known to mediate the effects of various vasodilating substances on glomerular mesangial cells. However, little is known about the role of soluble guanylate cyclase (SGC) in these cells in diabetes. We, therefore, investigated the changes in SGC activity as well as the cGMP content in rat mesangial cells (MC) cultured under high glucose or hypertonic conditions. The following results were obtained. 1. Sodium nitroprusside (SNP) (10(-4) M, 10min.) increased cyclic GMP (cGMP) content in MC from 8.17 +/- 0.99 pmol/mg protein to 981.6 +/- 86.3. 2. SNP (10(-4) M) stimulated SGC activity from 38.3 +/- 10.8 pmol cGMP formed/mg protein/10 minutes to 74.4 +/- 5.2. 3. In the coincubation experiment with bovine aortic endothelial cells, bradykinin (10(-6) M, 10min.) increased cGMP content in MC from 6.24 +/- 1.35 to 348.3 +/- 45.3. However, 4. the activity of SGC and SNP-induced increase of cGMP were not influenced by culturing MC in high glucose or hypertonic media. Similarly, the cGMP increase in MC coincubated with BAEC under bradykinin stimulation was not altered by culturing under high glucose or hypertonic conditions. These data suggested that SGC may play an important role in the regulation of cGMP content in MC. However, this enzyme may not be involved in the increase of cGMP content in MC cultured under high glucose condition.
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PMID:[Effect of glucose on soluble guanylate cyclase in cultured rat mesangial cells]. 810 Feb 85


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