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

The effects of non-insulin-dependent diabetes mellitus (NIDDM) were investigated on the reactivity of human internal mammary artery (IMA) and saphenous vein (SV) rings obtained from coronary artery patients (CAP) undergoing coronary artery bypass surgery. In the presence of endothelium, the maximal contractile response and sensitivity (pD2) of IMA or SV to NA and ET-1 significantly increased in CAP with NIDDM relative to CAP only (controls). Removal of the endothelium markedly and significantly enhanced the maximal contractile response and sensitivity of IMA or SV to NA in CAP only, but did not induce a significant alteration in CAP with NIDDM compared to that in the presence of endothelium. The maximal contractile response and sensitivity of diabetic vessels with or without endothelium to NA were similar to values of corresponding vessels without endothelium obtained from nondiabetic CAP. The maximum contractions developed by NA or ET-1 were much greater in SV than that determinated in the IMA. Acetylcholine (ACh) and histamine produced endothelium-dependent relaxations in precontracted IMA and these effects of ACh and histamine significantly decreased in CAP with NIDDM. Endothelium-dependent relaxations stimulated by ACh were more pronounced in IMA than that determinated in the SV. In precontracted SV, histamine induced marked contractions that were significantly greater in CAP with NIDDM relative to CAP only. Endothelium-independent relaxations of vessels to sodium nitroprusside (SNP) were not influenced by NIDDM. Data indicate that NIDDM causes a deficit in the vasorelaxant activity of endothelium, leading to an increase in contractility of human IMA and SV. Data also suggest that IMA can be a better choice of graft for coronary occlusive disease than SV, specially in patients with NIDDM.
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PMID:Effects of non-insulin dependent diabetes mellitus on the reactivity of human internal mammary artery and human saphenous vein. 760 92

Streprozotocin diabetes and extracerebral insulin affect acetyl-CoA and acetylcholine metabolism in the brain. In the present study we have shown that pyruvate utilization, acetyl-CoA content and ACh synthesis in nerve terminals from diabetic rats were 45, 30 and 50%, respectively, higher than that in healthy animals. Treatment with insulin normalized pyruvate utilization and acetylcholine synthesis but did not decrease the acetyl-CoA level. 3-Hydroxybutyrate did not affect acetyl-CoA and acetylcholine metabolism in control rats. However, in diabetic animals, 3-hydroxybutyrate significantly increased supply of acetyl-CoA for acetylcholine synthesis. These data provide evidence that increased provision of acetyl-CoA is prerequisite for activation of acetylcholine synthesis in diabetic brain.
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PMID:Acetylcholine synthesis in nerve terminals of diabetic rats. 769 72

ATP-sensitive potassium channels (KATP) are the ion channels which are closely associated with cellular metabolism. A number of chemical compounds which block KATP facilitate the release of hormones or neuropeptides. For example, KATP-blocking agents such as antidiabetic sulfonylureas and imidazolines stimulate insulin secretion from pancreatic beta-cells by decreasing KATP activity. On the other hand, so-called potassium channel openers, KATP-activating drugs which constitute a chemically diverse group of compounds, inhibit growth hormone secretion from anterior pituitary cells and release of gamma-aminobutylic acid from substantia nigra. Several endogenous substances also modulate release of hormone or neuropeptide by affecting KATP activity. Acetylcholine and histamine stimulate the release of endothelium-derived hyperpolarizing factor, which activates KATP in the plasma membrane of vascular smooth muscle cells. Both galanin and somatostatin inhibit insulin release from pancreatic beta-cells by opening KATP through the activation of G-protein. Glucagon-like peptide-1[7-36], which stimulates insulin secretion by indirectly blocking KATP in beta-cells, shows antidiabetic effects in patients with non-insulin-dependent diabetes mellitus. Endosulphine, an endogenous inhibitor of KATP, stimulates insulin secretion from pancreatic beta-cells. Accumulating knowledge of the modulation and function of KATP would help our understanding of the regulation and physiological role of hormones and neuropeptides.
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PMID:[ATP-sensitive potassium channel and hormone/neuropeptide]. 779 22

Cardiovascular complications of diabetes mellitus account for 80% of deaths among diabetics. Autonomic neuropathy increases the susceptibility of the diabetic myocardium to arrhythmias. Decreased contractility of diabetic myocardium is associated with intracellular calcium overload. However, the relationship between calcium levels and myocardial cholinergic responses is not known. This study was undertaken to observe the effect of felodipine 5 mg/kg on myocardial function and cholinergic responses of the spontaneously working isolated heart of rats with short term streptozotocin-diabetes. Felodipine was administered (po) for 4 week to rats with streptozotocin-diabetes of 4 week duration. Felodipine did not alter the blood glucose levels. The increased cardio-somatic ratio in diabetic rats was attenuated by felodipine. Diabetic status was associated with decreased coronary flow and felodipine increased coronary flow in diabetic rat hearts both before and after ACh. It may be concluded that felodipine favourably altered the adverse myocardial pathology in experimental diabetes, and this strengthens its use as an antihypertensive in diabetics.
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PMID:Effect of felodipine on myocardial function and cholinergic responses in short term streptozotocin diabetes in rats. 781 41

The present study was aimed at investigating the atrial natriuretic peptide (ANP) and urinary responses to acute perturbations in fluid balance and the vascular function in diabetes mellitus (DM). DM was induced in rats by treatment with streptozotocin (50 mg/kg, i.p.). Ten weeks later, the plasma ANP concentration measured in the conscious state was significantly higher in DM group (27.5 +/- 3.9 pg/mL) than in the control (15.4 +/- 2.6 pg/mL), while the atrial tissue contents of ANP were lower. In response to acute extracellular volume expansion (VE), amounting up to 5% of body weight over 45 min, under thiopental anesthesia (50 mg/kg, i.p.), the magnitude of increase in plasma ANP was lower in the DM group than in the control (56.8 +/- 25.2 vs. 189.1 +/- 53.6% increases over the basal). Urinary sodium excretion during VE was also lower in the DM group. Acetylcholine-induced relaxation of the isolated aortic rings was attenuated in the DM group, which was partially restored by L-arginine-supplementation (2 g/L in drinking water). These results suggest that body fluid homeostasis and vascular functions are unfavorably altered in DM.
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PMID:Attenuated release of atrial natriuretic peptide and vasorelaxation in streptozotocin-induced diabetic rats. 798 84

1. Noradrenaline sensitivity and relaxation to acetylcholine were investigated in the isolated perfused mesentery and in aortic rings of control and streptozotocin (STZ)-induced (50 mg kg-1) diabetic Charles River rats. 2. In addition, noradrenaline sensitivity and acetylcholine relaxation were similarly assessed in streptozotocin-induced diabetic rats treated from the time of onset of diabetes with the aldose reductase inhibitor, ponalrestat (100 mg kg-1 day-1). 3. The untreated diabetic rats (2-10 weeks after injection of STZ) demonstrated enhanced vascular sensitivity to noradrenaline in the perfused mesenteric arterial tree, compared with age matched controls (pEC50 [-log concentration (M)]: diabetic 5.62 +/- 0.09, n = 18, versus control 5.23 +/- 0.07, n = 16, P < 0.01). 4. Acetylcholine-induced relaxation was significantly impaired in the perfused mesentery of the diabetic animals compared to controls (pED50 [-log dose (mol)]: diabetic 9.87 +/- 0.10, n = 20, versus controls, 10.29 +/- 0.09, n = 20, P < 0.05). 5. In contrast, the aortic ring preparations demonstrated no significant functional differences between the diabetic and control groups in response to either noradrenaline (pEC50: diabetic 7.66 +/- 0.08, n = 15, versus controls 7.55 +/- 0.06, n = 15, NS), or acetylcholine (pEC50: diabetics 7.30 +/- 0.06, n = 15, versus controls 7.40 +/- 0.09, n = 15, NS). 6. Treatment with the aldose reductase inhibitor, ponalrestat, did not affect the increased vascular reactivity to noradrenaline, or impaired relaxation to acetylcholine in the perfused mesentery.
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PMID:Endothelial function in the isolated perfused mesentery and aortae of rats with streptozotocin-induced diabetes: effect of treatment with the aldose reductase inhibitor, ponalrestat. 801 23

We examined the effect of three distinct depolarizing conditions on [3H]ACh release from cardiac postganglionic parasympathetic neurons in age-matched controls and insulin-treated STZ-induced diabetic rats to determine whether alterations in neurotransmitter release were present in the diabetic group. The effect of TTX, which exerts a use- and voltage-dependent block of sodium channels, was examined on the release of ACh stimulated by SRIF14 (preferentially acts at the cell body). We also studied the effect of STZ-induced diabetes on [3H]ACh release by the relatively site-specific depolarizing agent VT (preferentially acts at the axon) and high potassium (non-site-specific). Basal, SRIF14-(10(-7) M), VT-(10(-4) M), and K+ (100 mM)-stimulated [3H]ACh release was similar in control and STZ-induced diabetic animals. However, in STZ-induced diabetic but not control rats, SRIF14-induced [3H]ACh release was resistant to TTX (2 x 10(-7) M). In addition, the response to submaximal K+ (25 mM) stimulation was greater in STZ-induced diabetic compared with control animals. Treatment with insulin corrected these abnormalities. These data indicate that in the acute STZ-induced diabetic rat, SRIF14-, VT-, and high K(+)-evoked release of ACH is not impaired, which suggests that the mechanisms associated with ACh storage and release in postganglionic cardiac parasympathetic neurons are not affected in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Jan
PMID:Abnormal agonist-stimulated cardiac parasympathetic acetylcholine release in streptozocin-induced diabetes. 809 4

Diabetes was induced in rats by an injection of streptozotocin (55 mg/kg). Endothelium-dependent relaxations in mesenteric resistance arteries (luminal diameter 210 +/- 20 microns) of control and diabetic rats were compared in myographs. Acetylcholine induced endothelium-dependent relaxations that were mediated by nitric oxide (EDNO). EDNO-mediated relaxations were impaired in diabetic arteries; concentrations of acetylcholine required to produce 50% relaxation (ED50) of activated arteries were 5 nM in control and 13.5 nM in arteries from diabetic rats studied after 6 wk (P < 0.05). The impairment in relaxation worsened with duration of the diabetes; ED50 for acetylcholine increased to 63 and 100 nM in diabetic arteries studied after 16 and 24 wk of diabetes, respectively. NG-nitro-L-arginine produced 5.5- and 16-fold decreases in sensitivity of control and diabetic arteries to acetylcholine. NG-nitro-L-arginine produced at least as much inhibition of acetylcholine relaxations in diabetic arteries, indicating that the impaired relaxation noted in diabetic arteries does not result from decreased production of EDNO. EDNO-mediated relaxations in diabetic arteries were impaired by increased production of endothelium-derived free radicals. Superoxide dismutase, a scavenger of superoxide anion, and dimethylthiourea, a scavenger of hydroxyl radicals, normalized EDNO-mediated relaxations in diabetic arteries. The ED50 values for acetylcholine were 13.5, 5.5, and 4 nM for untreated and SOD- and DMTU-treated diabetic arteries, respectively (P < 0.05 for treated vs. untreated arteries). Superoxide anion and hydroxyl radicals appear to block EDNO-mediated relaxation by inactivating EDNO.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelial dysfunction in mesenteric resistance arteries of diabetic rats: role of free radicals. 816 Aug 18

The purpose of this study was to compare vascular responsiveness in young (12 week old), aging hyperinsulinemic-glucose intolerant (52 weeks old) and diabetic (streptozotocin; 14 weeks old) rats. Aortic rings with and without endothelium were maintained in organ chambers for isometric tension recording. The contractile response to KCl was significantly enhanced in aortae from diabetic animals when compared to the responses obtained in young and old ones. The contractile response to norepinephrine or U46619, was significantly shifted to the right in the aortae from aging animals, however the aortae from these hyperinsulinemic rats were hyperresponsive to serotonin. Acetylcholine and ADP provoked an endothelium-dependent relaxation which was markedly depressed in the aortae from diabetic animals. The relaxation to ADP was selectively inhibited in the aging animals. The effect of sodium-nitroprusside was not significantly different in the three groups. Isoproterenol and forskolin induced endothelium-independent relaxation. Isoproterenol responses were inhibited in aging and diabetic animals, however the forskolin-relaxation was inhibited only in the aortae from aging animals. These results suggest that in two models of diabetes (i.e. Type I insulin-dependent and type II non insulin-dependent) vascular responsiveness is differently affected. Aging hyperinsulinemic animals present a selective hyperresponsiveness to serotonin, a selective dysfunction of ADP-induced endothelium-dependent relaxation and smooth muscle adenylate cyclase deficit. In diabetic animals a beta adrenergic hyporesponsiveness, not linked to adenylate-cyclase dysfunction, and non-selective depression of endothelium-dependent responses can be observed.
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PMID:Vascular responsiveness in young, diabetic, and aging hyperinsulinemic rats. 819 94

Rats were fed for 10 days with a 40% galactose diet, in order to chronically stimulate the polyol pathway. Thoracic aorta contraction and relaxation were studied. Compared to controls, galactosaemia did not influence contractions to phenylephrine or serotonin. Acetylcholine produced concentration-dependent relaxation of aortic rectangles precontracted with phenylephrine; galactosaemia caused a 25% deficit in maximum relaxation to acetylcholine (P < 0.01) and a 168% increase in EC50. There was a similar 25% reduction in relaxation to 3 microM calcium ionophore A23187 (P < 0.05). By contrast, there were no significant differences in endothelium-independent relaxation to nitroglycerine or cromakalim. The abnormalities in endothelium-dependent relaxation were completely prevented by treating galactosaemic rats with the aldose reductase inhibitor, ponalrestat. Thus, the data demonstrate that elevated polyol pathway activity contributes to reduced endothelium production, release or the action of nitric oxide in experimental galactosaemia, and suggest that this mechanism could also contribute to the vascular defects seen in diabetes mellitus.
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PMID:Contraction and relaxation of aortas from galactosaemic rats and the effects of aldose reductase inhibition. 825 24


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