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

Diabetes and hypertension have a higher than expected comorbidity. They share common etiology, pathophysiology, and organ effects. Long-term therapeutic goals are to prevent renal failure and atherosclerosis. Management should inhibit pathophysiologic mechanisms and avoid stimulating them. The most appropriate pharmacologic agents to treat hypertension in the diabetic are ACE inhibitors, selected calcium channel blockers, alpha adrenengic blockers, and certain central alpha agonists. The only diuretics that should be used are indapamide and torsemide.
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PMID:Diabetes and hypertension. 856 30

This study was designed to investigate the effects of the calcium channel blocker manidipine on insulin-dependent glucose uptake (insulin sensitivity) and insulin action to renal sodium handling and pressor systems in essential hypertensive (EHT). Seven EHT were hospitalized and a 2-h euglycemic hyperinsulinemic glucose clamp was performed in a fasting condition before and after 2 weeks administration of manidipine (20 mg/day). Insulin sensitivity was evaluated as M-value calculated from the infusion rate of glucose. Manidipine administration decreased mean blood pressure and increased M-value significantly in EHT. Before the manidipine treatment, hyperinsulinemia during the clamp induced a decrease of urinary sodium excretion and increases of plasma norepinephrine and plasma renin activity in EHT. After manidipine treatment, however, hyperinsulinemia induced natriuresis and did not augment the pressor systems activity. Thus, the calcium channel blocker improved insulin resistance as assessed by glucose clamp technique in EHT. Suppression of augmented renal sodium reabsorption and pressor system activities of insulin may be connected with the hypotensive mechanisms and the natriuresis caused by calcium channel blockers.
J Diabetes Complications
PMID:Effects of a calcium channel blocker, manidipine, on insulin sensitivity in essential hypertensives. 857 30

This study was done to examine the acute effect of a calcium channel blocker on renal hemodynamics in the diabetic spontaneously hypertensive rat (SHR). Streptozotocin was used to induce diabetes, and barnidipine (B) was used as a calcium blocker. Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by a clearance method with paraaminohypurate (PAH) and inulin, respectively. Rats were divided into two groups: nondiabetic SHR, N-SHR; diabetic SHR, DM-SHR. B increased RBF in N-SHR (7.44 +/- 1.99 versus 8.50 +/- 1.97 mL/min/g.kw) while there was no change in DM-SHR. B reduced renovascular resistance (RVR) in DM-SHR and N-SHR. B increased GFR in N-SHR (1.15 +/- 0.24 versus 1.34 +/- 0.25 mL/min/g.kw), in spite of no changes in DM-SHR. B did not modify filtration fraction (FF) in both groups. These results indicate (1) in SHR, B exerts beneficial effects on hypertensive renal damage by reducing mean arterial pressure (MAP), RVR, RBF, and GFR; (2) in diabetic SHR, B is less effective in restoring renal hyperfiltration in spite of reducing RVR.
J Diabetes Complications
PMID:Acute effect of calcium blocker on renal hemodynamics in diabetic spontaneously hypertensive rat. 857 52

Several studies have shown that lowering of blood pressure slows the rate of progression of diabetic renal disease. Some placebo-controlled studies have also shown that angiotensin-converting enzyme (ACE) inhibitors decrease or stabilize albuminuria in incipient nephropathy and slow the rate of progression of advanced nephropathy. However, it is not yet clear if prolonged treatment with ACE inhibitors or with other agents exerts a specific renoprotective effect in incipient diabetic nephropathy. It is proposed that such an effect should be independent from changes in systemic blood pressure and should be characterized by amelioration of the rate of rise of albumin excretion rate (AER) and the rate of fall of glomerular filtration rate (GFR) and independence from changes in other parameters known to influence AER (glycemic control, protein intake, sodium intake). In addition, there should be evidence that the potentially reversible effects of therapeutic intervention on AER and GFR are translated to long-term changes in renal function and structure. This paper reviews the evidence on which the concept of renoprotection is based, with particular reference to choice of end points, heterogeneity of study groups, and complexities of the disease process, and relates this evidence to the natural history of nephropathy in type I and type II diabetes. Based on the above, an assessment is made of the comparative effects of ACE inhibitors and other antihypertensive agents on AER and GFR. It is suggested that longitudinal intra-individual analysis of both variables may be necessary in order to determine whether ACE inhibitors exert greater renoprotection than calcium channel blockers or other antihypertensive agents.
J Diabetes Complications
PMID:Natural history of early diabetic nephropathy: what are the effects of therapeutic intervention? Melbourne Diabetic Nephropathy Study Group. 857 54

Accumulation of sorbitol and xylitol in rat lenses incubated in medium-199 with and without verapamil has been studied. This antihypertensive drug, known to attenuate hypertension by its calcium channel blocking effect, is also known to inhibit cataract formation in diabetes. The present studies have demonstrated that verapamil's effect against cataract could also be partially related to its aldose reductase inhibitory activity, in addition to the Ca++ channel blocking activity. The accumulation of sorbitol in the lenses incubated with high glucose in the presence of 400 microM verapamil was only 2.3 mmoles/Kg wet weight against 11.3 mmoles/Kg in its absence. The level of xylitol attained in the presence of 10 mM xylose was 25.7 +/- 2.4 mmoles/Kg. It decreased to 4.8 +/- 1.2 mmoles/Kg in presence of 400 microM verapamil. Hence, verapamil is significantly effective in inhibiting lens aldose reductase dependent polyol synthesis, an action simultaneous with its effect on calcium penetration.
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PMID:Inhibition of polyol formation in rat lens by verapamil. 857 16

The maintenance of adequate hemodialysis vascular access is frequently complicated in the patient with polytetrafluoroethylene (PTFE) A-V hemodialysis grafts by venous anastomotic stenosis. This stenosis is caused by neointimal hyperplasia (NIH), a response to vascular injury. In this study, the authors prospectively analyzed the effect of a short-term regimen consisting of administration of two medications, heparin and low molecular weight dextran, on the development of NIH at the venous anastomosis in 79 patients with PTFE A-V hemodialysis grafts. In addition, they evaluated other parameters' effects on the development of NIH. In comparison with control subjects, heparin had some effect in minimizing the development of NIH in the PTFE grafts when evaluated radiologically at 3 months, although this effect was not statistically significant. Low molecular weight dextran, however, had no trend or statistically significant effect on this venous anastomotic narrowing. Interestingly, patient age, use of calcium channel blockers, and presence of diabetes mellitus (DM) all appeared to affect the development of NIH. Increasing age and use of calcium channel blockers was associated with decreased development of NIH; conversely, DM was associated with worsened NIH. In evaluation of access survival (time to first access failure), degree of venous anastomosis stenosis at 3 months was not predictive. Patient time on dialysis pre graft placement was the only measured parameter related to access failure. The method of dialysis pre graft placement (hemodialysis versus peritoneal dialysis) was not a significant factor in early access failure. Pharmacologic treatment of venous anastomotic narrowing in PTFE hemodialysis grafts due to NIH continues to be difficult. Short-term treatment with the tested medication failed to statistically affect NIH. Patient age, use of calcium channel blockers, and presence of DM were all factors in the development of NIH. Of measured parameters, time on dialysis pre graft placement was the only factor correlated with early access failure. In future treatment regimens, one should consider more prolonged treatment. In addition, noted risk factors should be considered when determining type of renal replacement therapy.
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PMID:Maintenance of adequate hemodialysis access. Prevention of neointimal hyperplasia. 858 64

We compared the renoprotective effect between angiotensin-converting enzyme inhibitor, enalapril, and a dihydropyridine-type calcium channel blocker, nicardipine, in a severe form of renal injury in rats. Two-day-old spontaneously hypertensive rats (SHR) were injected with streptozotocin or vehicle as control. UNX was performed at 3 weeks of age, and enalapril or nicardipine was administered in drinking water from 7 weeks of age. Uninephrectomy (UNX) markedly exacerbated hypertension and renal injury in the nondiabetic and diabetic SHR. Enalapril and nicardipine comparably reduced blood pressure in UNX diabetic SHR. However, serum creatinine was significantly elevated in the nicardipine-treated group as compared with the enalapril-treated group at 24 weeks of age (nicardipine-treated group, 67 +/- 4 microM; enalapril-treated group, 49 +/- 3 microM; P < 0.01; untreated group 57 +/- 4 microM). Furthermore, the incidence of glomerular sclerosis was similar between untreated and nicardipine-treated groups, whereas it tended to be reduced in the enalapril-treated group. In a separate experiment of diabetic SHR without UNX, enalapril therapy significantly ameliorated hyperglycemia and albuminuria (P < 0.01). This study showed that a renoprotective effect was seen in enalapril but not in nicardipine in UNX diabetic SHR despite the comparable reduction of blood pressure. This suggests that enalapril may be more effective than nicardipine in delaying the progression of a severe form of diabetic nephropathy.
Diabetes Res Clin Pract 1995 Sep
PMID:Renoprotective effect of enalapril in uninephrectomized spontaneously hypertensive rats with neonatal streptozotocin-induced diabetes. 859 7

The effectiveness of the tocolytic agent and other betamimetic drugs in the treatment of preterm labor remains controversial. Effectiveness or efficancy of ritodrine has not yet convincingly been proven. A major concern are the marked side effects of beta-mimetics. The calcium channel blocker nifedipine has been used for tocolysis shortly after its introduction in clinical practice and is considered to be a probable good alternative for ritodrine. The efficacy of nifedipine versus ritodrine in the treatment of preterm labor was assessed in a retrospective study. 32 patients received intravenous ritodrine and 29 oral nifedipine. As endpoints were used: postponement of delivery, maternal side effects and perinatal outcome. The results of this retrospective study suggest that nifedipine is more successful in postponing delivery than ritodrine. Maternal side effects seemed to occur more frequently and be more serious in patients treated with ritodrine as compared to nifedipine. Perinatal outcome seemed better in the nifedipine group than in the ritodrine group. The promising data from small prospective studies and the results of this retrospective study warrant further large prospective studies on the definitive place of nifedipine in the treatment of premature labor. Until the results of such a trial are available we advocate the use of nifedipine in case of preterm labor, especially in a patient with diabetes mellitus, ruptured membranes, cardiac disease or multiple pregnancy, in order to avoid the characteristic side effects of beta-mimetics.
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PMID:Ritodrine and nifedipine as tocolytic agents: a preliminary comparison. 860 48

Catecholamines are known to stimulate calcitonin secretion in C-cells by a receptor mediated pathway, but details regarding the postreceptor events are unknown. Since norepinephrine (NE) influences intracellular calcium concentration [Ca2+]i and cAMP levels in C-cells, we used different adrenergic agonists and antagonists to investigate the effect of NE on [Ca2+]i and cAMP accumulation, and on calcitonin secretion in rat MTC-6-23 cells. NE stimulated intracellular cAMP accumulation and calcitonin secretion dose-dependent, with 10(-7) mol/l causing maximal stimulation. The NE induced increase in cAMP accumulation/calcitonin secretion could be decreased to baseline by equimolar amounts of the beta-adrenergic blocker propanolol. The alpha-blocker phentolamine did not significantly influence NE stimulated calcitonin secretion even at high concentrations. The beta-adrenergic agonist fenoterol proved to be as effective as NE in stimulating cAMP accumulation/calcitonin secretion. Activation of inhibitory G-proteins by the adenosine A1 receptor analogue N6-phenylisopropyladenosine at 10(-6) mol/l completely blocked NE stimulated calcitonin secretion. NE stimulated calcitonin secretion was also completely blocked by the cAMP antagonist RpcAMPs. The calcium channel blocker verapamil significantly inhibited NE stimulated calcitonin secretion, but interestingly increased NE stimulated cAMP accumulation. We conclude that NE induced calcitonin secretion is mediated through beta-receptors coupled to adenylate cyclase via G-proteins. cAMP and changes in [Ca2+]i are necessary for NE induced calcitonin secretion. There seems to be a complex interaction between the two pathways even regarding events occurring distal to cell membrane.
Exp Clin Endocrinol Diabetes 1996
PMID:Norepinephrine induced calcitonin secretion in rat medullary thyroid carcinoma 6-23 cells: interaction between intracellular calcium and cAMP. 875 May 70

The pregnancy complication characterized by proteinuric hypertension is called preeclampsia. Preeclampsia, an important cause of maternal and perinatal death, has an onset and progression impossible to predict. Termination of pregnancy is the only cure of preeclampsia. It is indicated when the fetus can survive outside the uterus or when the maternal condition deteriorates to such a condition that continuation would bring greater harm to the mother. The etiology of preeclampsia is unknown. Preeclampsia appears to be linked to abnormal trophoblastic implantation. In normal pregnancies, implantation effects changes in the spiral arteries that supply the intervillous space and fibrin-containing trophoblast, and amorphous matrix replace the endothelium and the internal elastic lamina. These changes do not occur or are limited in pre-eclamptic women. There appears to be a familial tendency to preeclampsia. Impaired formation of blocking antibodies to antigenic sites on the placenta increases the risk of pre-eclampsia. Risk factors are primigravidity, short duration of sexual cohabitation before conception, abundance of trophoblastic tissue (e.g., multifetal and molar pregnancies), and underlying vascular disease as in diabetes. Poor placental perfusion may account for the increase in maternal blood pressure. Preeclampsia can lead to eclampsia, cerebral hemorrhage, coagulopathy, and death. Poor utero-placental circulation retards fetal growth and causes fetal distress and maybe even perinatal death. When the diastolic blood pressure is higher than 110 mmHg, pre-eclamptic women should be administered antihypertensive drugs (e.g., methyldopa, beta-blockers, calcium channel blockers, hydralazine, labetatol, or diazoxide) to prevent maternal complications, but these drugs do not improve utero-placental blood flow nor do they prevent proteinuria. Diuretics should not be administered. Proteinuria indicates that the kidneys have been affected. A large randomized trial shows that aspirin does not effectively prevent preeclampsia. Routine calcium supplementation does appear to prevent it and preterm delivery.
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PMID:Pre-eclampsia. 875 7


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