Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mortality and morbidity from coronary heart disease (CHD), diabetes mellitus (DM) and essential hypertension (HTN) are higher in people of South Asian descent than in other groups. There is evidence to believe that essential fatty acids (EFAs) and their metabolites may have a role in the pathobiology of CHD, DM and HTN. Fatty acid analysis of the plasma phospholipid fraction revealed that in CHD the levels of gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low, in patients with HTN linoleic acid (LA) and AA are low, and in patients with non-insulin dependent diabetes mellitus (NIDDM) and diabetic nephropathy the levels of dihomo-gamma-linolenic acid (DGLA), AA, alpha-linolenic acid (ALA) and DHA are low, all compared to normal controls. These results are interesting since DGLA, AA and EPA form precursors to prostaglandin E1, (PGE1), prostacyclin (PGI2), and PGI3, which are potent platelet anti-aggregators and vasodilators and can prevent thrombosis and atherosclerosis. Further, the levels of lipid peroxides were found to be high in patients with CHD, HTN, NIDDM and diabetic nephropathy. These results suggest that increased formation of lipid peroxides and an alteration in the metabolism of EFAs are closely associated with CHD, HTN and NIDDM in Indians.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Essential fatty acid metabolism in patients with essential hypertension, diabetes mellitus and coronary heart disease. 764 60

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with an increased risk of macro- and microvascular degenerative complications. Gliclazide is a second generation sulfonylurea that is widely used in the treatment of type II diabetes mellitus. Its hypoglycemic activity is well documented. In addition to its metabolic effects, gliclazide has beneficial effects on the hemobiological abnormalities of NIDDM. These effects are mediated by the azabicyclo-octyl ring grafted on to its aulfonylurea core. Numerous studies have demonstrated that gliclazide reduces platelet hyperadhesion and platelet hyperaggregability. These actions have been extensively confirmed in diabetic patients over periods of up to 3 years. With regard to platelet functions, several groups have demonstrated a significant reduction in serum and intraplatelet beta thromboglobulin and thromboxane B2. In animal models, in-vitro and in-vivo gliclazide stimulates endothelial prostacyclin synthesis. The beneficial effects of the compound on thromboxane/prostacyclin balance have been recently confirmed in type II diabetic patients after a 3-month treatment period. Concerning fibrinolysis, gliclazide restores low plasminogen activity to normal in NIDDM patients previously treated with first-generation sulfonyl-ureas. Gliclazide increases fibrinolytic potential by increasing endothelial cell tissue plasminogen activator and pre-kallikrein activity. More recent studies suggest that gliclazide may have effects on fibrin network structure, rendering the fibrin more amenable to fibrinolysis. Finally, it has been shown that gliclazide has a potent free-radical-scavenging activity in vitro. This property has been recently confirmed in vivo in type II diabetic patients and may suggest that platelet reactivity and oxidative stress are related in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemobiological properties of gliclazide. 783

In uterine tissue obtained from castrated control and non-insulin dependent diabetic (NIDDM) rats, eicosanoid production and its regulation by glucose levels and by the activity of phospholipase A2 (PLA2) was assessed. Basal outputs of prostaglandins (PGs) PGE2, PGE1, PGF2 alpha, 6-keto-PGF1 alpha (indicating the production of prostacyclin), thromboxane B2 (TXB2) (indicating the generation of TXA2) and leukotriene B4 (LTB4) were similar in control and NIDDM uterine preparations as assessed by RIA. When uterine conversion of labelled arachidonate into different prostanoids was evaluated, generation of 6-keto-PGF1 alpha, PGE2 and PGF2 alpha was similar in control and NIDDM uterine tissue, while TXB2 production was higher in the diabetic group. Moreover, when control tissue was incubated in the presence of elevated concentrations of glucose (22 mM) and compared to control tissue incubated in concentrations of glucose 11 mM, similar generation of 6-keto-PGF1 alpha, PGE2 and PGF2 alpha was observed, and higher concentrations of TXB2 were found, similar to those observed in diabetic uterine tissue. When NIDDM uterine tissue was incubated in the presence of glucose 22 mM, no difference in any prostanoid evaluated was observed when compared to values obtained in the presence of glucose 11 mM. In this work we have observed in NIDDM uterine tissue a normal TXA2 production when evaluated by RIA from endogenous arachidonic acid (AA) and a higher TXA2 generation from exogenous labelled AA. In addition PLA2 activity was found diminished in the NIDDM uteri in comparison to control uteri. A role of the diminished PLA2 as a protective mechanism that avoids TXA2 overproduction in uterine tissue from NIDDM rats is discussed.
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PMID:Eicosanoid production and phospholipase A2 activity in uterine tissue from castrated rats with non-insulin dependent diabetes mellitus. 859 72

The acute effects of beraprost sodium (sodium (+/-)-(1R*, 2R, 3aS*, 8bS*)-2, 3, 3a 8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-I- octen-6-ynyl] -1H-cyclopenta [b] bensofuran-5-butyrate), a stable analogue of prostaglandin I2 which works as a vasodilator and anti-platelet agent, were investigated in patients with non-insulin dependent diabetes mellitus. Its effects on the dorsal pedis artery were examined using a new real-time two-dimensional Doppler ultrasonographic technique and by laser blood flowmetry. Before and 60 min after oral administration of beraprost sodium (Dolner 40 micrograms) and elastase (Elaszym 1800 U), the cross-sectional area (CSA) of the dorsal pedis artery and its blood flow index (BFI), calculated from the maximum flow velocity and area, were determined. Dermal microcirculatory blood volume (MBV) was also measured by laser blood flowmetry. In the beraprost sodium group, the CSA, BFI and MBV were significantly increased, while in the elastase group, no significant changes were observed. These result suggest that beraprost sodium has a beneficial effect on diabetic macro- and microangiopathy.
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PMID:Acute effect of beraprost sodium on lower limb circulation in patients with non-insulin-dependent diabetes mellitus-evaluation by color Doppler ultrasonography and laser cutaneous blood flowmetry. 894 5

Prostacyclin (PGl2) generated by vascular endothelial cells play an important role in the maintenance of vessel wall homeostasis. Human plasma-derived serum (PDS) stimulated PGl2 synthesis by both cultured bovine aortic endothelial cells (BAEC) and adrenal capillary endothelial cells (BCEC), but the PGl2 response of the latter cells was far smaller. When BAEC were cultured with a high concentration of glucose (400 mg/dl), the PGl2 synthesis induced by 20% PDS was significantly lower than in the culture with a physiological concentration of glucose (100 mg/dl) (258 +/- 45 pg/10(4) cells/h vs. 402 +/- 52 pg/10(4) cells/h, n = 4, P < 0.05). On the other hand, there was no significant difference in the PDS-induced PGl2 synthesis between BCEC cultured with high and physiological concentrations of glucose. Additionally, 10% PDS obtained from patients with non-insulin dependent diabetes mellitus (n = 6) stimulated significantly less PGl2 synthesis than that from healthy subjects (n = 4) in the case of both BAEC (133 +/- 27 pg/10(4) cells/h vs. 402 +/- 38 pg/10(4) cells/h, P < 0.05) and BCEC (72 +/- 15 pg/10(4) cells/h vs. 118 +/- 12 pg/10(4) cells/h, P < 0.05), with the difference in PGl2 synthesis being smaller for BCEC. These findings indicate that the PDS-induced PGl2 synthesis differs between cultured vascular endothelial cells from large and small vessels with the decrease in PGl2 by diabetic PDS and high glucose being more marked for BAEC than BCEC.
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PMID:Difference in serum-induced prostacyclin production by cultured aortic and capillary endothelial cells. 904 36

Prostacyclin (PGI2) synthesis by vascular endothelial cells (ECs) decreases in diabetic subjects, possibly leading to the development of diabetic angiopathy, such as that seen in atherosclerosis. We recently found a novel bioactive peptide, prostacyclin-stimulating factor (PSF), which stimulates PGI2 synthesis by cultured aortic ECs. Our previous studies demonstrated that PSF is dominantly expressed by arterial smooth muscle cells (SMCs). In the present study, we found PSF to exist in the SMCs of human coronary arteries by means of immunohistochemical methods. Human coronary arteries obtained from autopsies were divided into four subgroups, with or without NIDDM and/or myocardial infarction. Immunostaining for PSF was performed by the avidin-biotin peroxidase complex method using a purified anti-PSF antibody, and the immunostaining for PSF was assessed semiquantitatively. PSF staining was markedly reduced in coronary arterial SMCs from patients with NIDDM and/or myocardial infarction. In addition, the effect of a high glucose culture on PSF mRNA expression and PSF production in bovine aortic SMCs was examined by immunocytochemical staining and both Western and Northern blot analyses. The immunostaining and immunoblot band for PSF also significantly decreased when bovine aortic SMCs were cultured with high concentrations of glucose. Furthermore, as compared with the SMCs cultured with a physiological glucose concentration, the density ratio of PSF mRNA to 28S rRNA expression significantly decreased when the SMCs were cultured with high concentrations of glucose. These results strongly suggest that the decreased PSF production may thus results in a decreased production of PGI2 in the coronary artery, thus leading to the development of both diabetic macroangiopathy and atherosclerosis.
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PMID:Immunohistochemical study of prostacyclin-stimulating factor (PSF) in the diabetic and atherosclerotic human coronary artery. 931 60

The autocrin-paracrin prostanoid system plays a major role in the enhancement or inhibition of renal tissue damage. Our hypothesis was that there might be circulating factors in the plasma with a capability to modify renal (glomerular) prostanoid synthesis. We measured the synthesis of prostacyclin 1-2 (PGI2) and thromboxan A-2 (TxA2) of isolated glomeruli, incubated in plasma samples obtained from hypertensive and diabetic (NIDDM) patients. It was found that these plasma samples decreased the renal PGI2/TxA2 ratio, mostly by decreasing glomerular PGI2 synthesis and, to a lesser extent, increasing the synthesis of TxA2. Our results demonstrate that circulating factors in hypertension and diabetes might play a role in renal damage seen in these conditions.
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PMID:Glomerular prostanoid production is modified by plasma samples of hypertensive and diabetic patients. 953 Apr 33

In an investigation of the involvement of prostanoids in the pathogenesis of nephropathy in type 2 diabetes, we repeatedly measured the urinary excretion of prostanoids in both diabetic and healthy rats as the rats aged. Seven rats of the Otsuka Long-Evans Tokushima Fatty strain were used as rats with a model of type 2 diabetes and seven rats of the Long-Evans Tokushima Otsuka strain were used as rats without diabetes. Thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1alpha, the amounts of which reflect renal production of TXA2 and PGI2, respectively, and PGE2 in urine collected in metabolic cages were assayed when rats were 14, 30, 46, and 54 weeks old. Plasma glucose and urinary protein excretion also were measured periodically. The mean plasma glucose concentration of the diabetic rats was higher than that of the healthy rats throughout the study. At 30 weeks and later, urinary protein excretion by the diabetic rats was greater than that of the healthy rats, and it increased with age. Urinary excretion of TXB2 by the diabetic rats was higher than that of the healthy rats at 14 weeks (52.4+/-23.5 vs. 27.0+/-2.6 ng/day; mean +/- SD, P = .015) and the difference continued to the end of the experiment. Urinary excretion of 6-keto-PGF1alpha by the diabetic rats was high at 14 weeks (52.3+/-12.8 vs. 26.9+/-4.6 ng/day; mean +/- SD, P<.001) but decreased with age and was the same as that of the healthy rats at 54 weeks. The urinary excretion of PGE2 by the two groups of rats was not significantly different. These results suggest that altered renal production of TXA2 and PGI2 is involved in the pathogenesis of diabetic nephropathy in rats with type 2 diabetes.
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PMID:Renal production of thromboxane and prostaglandins in a rat model of type 2 diabetes. 1067 Aug 25

Plasma endothelin-1, the nitric oxide (NO) mediator intraplatelet cyclic guanosine monophosphate (cGMP), the prostacyclin mediator cyclic adenosine monophosphate (cAMP) and the macrophage derived inflammatory mediator plasma neopterin were measured in men with Type 2 diabetes mellitus (n=91), impaired glucose tolerance (IGT; n=51), previously abnormal glucose tolerance (PAGT; n=20), and 34 healthy control men. Plasma endothelin-1was higher in men with Type 2 diabetes mellitus than in controls [4.1 (1.0-14.3) vs. 2.1 (0.2-8. 7) ng/l; P<0.001). Intraplatelet cGMP was higher in men with PAGT [0. 84 (0.57-2.76) pmol/10(9) platelets; P<0.05], IGT [0.85 (0.48-3.53); P<0.001] and Type 2 diabetes mellitus [0.90 (0.47-3.86); P<0.001] than in controls [0.70 (0.42-1.70]. No differences existed between groups concerning intraplatelet cAMP or plasma neopterin. Plasma endothelin-1 correlated with fasting plasma glucose (r=0.33; P<0.001) and HbA1(c) (r=0.29; P<0.001). In conclusion, elevated plasma endothelin-1 in Type 2 diabetes mellitus and its relationship to glucose and HbA1(c) suggest a putative role for endothelin-1 in diabetic endothelial cell damage. Increased cGMP indicating enhanced production/activity of NO suggests that factors other than reduced NO activity contribute to enhanced platelet aggregation in diabetes.
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PMID:Increased plasma endothelin-1 and intraplatelet cyclic guanosine monophosphate in men with disturbed glucose metabolism. 1096 Jul 23

Insulin resistance is a uniform finding in type 2 diabetes, as are abnormalities in the microvascular and macrovascular circulations. These complications are associated with dysfunction of platelets and the neurovascular unit. Platelets are essential for hemostasis, and knowledge of their function is basic to understanding the pathophysiology of vascular disease in diabetes. Intact healthy vascular endothelium is central to the normal functioning of smooth muscle contractility as well as its normal interaction with platelets. What is not clear is the role of hyperglycemia in the functional and organic microvascular deficiencies and platelet hyperactivity in individuals with diabetes. The entire coagulation cascade is dysfunctional in diabetes. Increased levels of fibrinogen and plasminogen activator inhibitor 1 favor both thrombosis and defective dissolution of clots once formed. Platelets in type 2 diabetic individuals adhere to vascular endothelium and aggregate more readily than those in healthy people. Loss of sensitivity to the normal restraints exercised by prostacyclin (PGI(2)) and nitric oxide (NO) generated by the vascular endothelium presents as the major defect in platelet function. Insulin is a natural antagonist of platelet hyperactivity. It sensitizes the platelet to PGI(2) and enhances endothelial generation of PGI(2) and NO. Thus, the defects in insulin action in diabetes create a milieu of disordered platelet activity conducive to macrovascular and microvascular events.
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PMID:Platelet dysfunction in type 2 diabetes. 1147 89


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