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)

Renal acid excretion and proximal and distal nephron acidification were evaluated 20 days after induction of diabetes, in rats, by intraperitoneal injection of streptozotocin (45 mg/kg). Titratable acidity in urine was measured by microtitration and ammonium excretion (NH4+) by spectrophotometry. Proximal tubular acidification was evaluated by the kinetics of reabsorption of perfused HCO3-. Distal nephron acidification was evaluated by measuring urine - blood pCO2 differences under alkaline overload. The net acid excretion (titratable acidity + NH4+ - HCO3-) was higher (p < 0.001) in diabetic rats (9.82+/-0.65 micromol/min/kg, n = 26) than in the control group (6.34+/-0.14, n = 24). Proximal HCO3- reabsorption was also higher (p < 0.001) in diabetic rats (8.38+/-0.11 nmol/cm2/s, n = 12) than in the control group (2.30+/-0.10, n = 22); however, evaluation of distal nephron H+ secretion by urine - blood pCO2 methodology was similar in both groups. We concluded that in rats with induced diabetes mellitus there is an increased rate of proximal HCO3- reabsorption, possibly effected by a higher density of Na+/H+ antiporter in the luminal membrane of the proximal tubule and by an increased proton-motive force of the H+ secretory mechanism. The higher rates of H+ secretion generate lower stationary proximal luminal pH and probably maintain the blood pH within the physiological range.
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PMID:Alterations of the renal handling of H+ in diabetic rats. 939 31

We previously reported the impaired HCO3- secretion and the increased mucosal susceptibility to acid in the duodenum of streptozotocin (STZ)-induced diabetic rats. In this study, we investigated the salutary effect of the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) on these changes and compared it with those of insulin. Animals were injected streptozotocin (STZ: 70 mg/kg, ip) and used after 1, 3-4, and 5-6 weeks of diabetes with blood glucose levels of > 300 mg/dL. Under urethane anesthesia the HCO3- secretion was measured in the proximal duodenal loop using a pH-stat method and by adding 10 mM HCl. L-NAME (20 mg/kg x 2) or insulin (4 units/rat) was administered sc for 4-5 weeks, starting 1 week after STZ treatment. The duodenal HCO3- secretory responses to various stimuli such as mucosal acidification (10 mM HCl for 10 min), 16,16-dimethyl prostaglandin E2 (dmPGE2: 10 micrograms/kg, i.v.), and vagal stimulation (0.5 mA, 2 ms, 3 Hz) were significantly decreased in STZ-treated rats, depending on the duration of diabetes. Repeated administration of L-NAME, starting from 1 week after STZ treatment, significantly reduced blood glucose levels toward normal values and restored the HCO3- responses to various stimuli in STZ rats, the effects being similar to those observed after supplementation of insulin. Diabetic rats developed duodenal lesions after perfusion of the duodenum with 150 mM HCl for 4 h, but this ulcerogenic response was significantly inhibited by the repeated treatment with L-NAME as well as insulin. We conclude that L-NAME is effective in ameliorating hyperglycemic conditions in STZ-diabetic rats, similar to insulin, and restores the impaired HCO3- secretion and the increased mucosal susceptibility to acid in diabetic rat duodenums.
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PMID:Impaired duodenal bicarbonate secretion in diabetic rats. Salutary effect of nitric oxide synthase inhibitor. 940 1

In this article, we report the assisting effect of lithium on hypoglycemic treatment in patients with diabetes. Thirty-eight diabetic patients, 15 male and 23 female, aged 20-70 yr, 33 noninsulin-dependent diabetes mellitus (NIDDM) patients, and 5 insulin-dependent diabetes mellitus (IDDM) patients, were recruited in this study. Fasting and 1-h postprandial blood glucose (BG) profiles were undertaken from three groups of patients with diabetes before and after short-term of treatment of lithium carbonate. Group I was treated with diet only, Group II with oral hypoglycemic agents (OHA), and Group III with insulin. The fasting blood glucose (FBG) level and 1-h postprandial blood glucose (1-h PBG) level before and after treatment of lithium were: Group I: FBG: 7.67 +/- 0.48 vs 7.13 +/- 0.82; 1-h PBG 15.13 +/- 0.88 vs 10.33 +/- 0.96; Group II: FBG: 8.84 +/- 0.67 vs 6.04 +/- 0.57; 1-h PBG: 12.33 +/- 0.72 vs 9.95 +/- 0.82; Group III: FBG: 10.87 +/- 0.83 vs 6.83 +/- 0.79; 1-h PBG: 12.45 +/- 0.93 vs 9.17 +/- 1.00 mmol/L, respectively. The FBG and PBG of all three groups decreased significantly after lithium treatment, except the FBG in Group I. These data suggest that combined with other therapy, lithium could improve glucose metabolism in most patients with diabetes. Our results suggest that lithium has an assisting hypoglycemic effect on antidiabetic treatment.
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PMID:Assisting effects of lithium on hypoglycemic treatment in patients with diabetes. 940 82

The present work was designed to identify the HCO3(-)-dependent alkalinizing carrier in ventricular myocytes of normal and diabetic adult rats and to determine to what extent this system contributes to acid-equivalent extrusion after an intracellular acidification. We also examined the possible influence of intracellular Ca2+ (Cai2-) and glycolytic inhibition on the carrier activation. Intracellular pH (pHi) was recorded using seminaphthorhodafluor-1. The NH4+ method was used to induce an intracellular acid load. Evidence is provided for the existence of a Cl(-)-independent Na(+)-HCO3- cotransport contributing to pHi recovery from an intracellular acid load in ventricular cells of adult rats. Na(+)-HCO3- cotransport accounts for 33% of the total acid-equivalent efflux (JHe) from normal adult myocytes after intracellular acidification at pHi 6.75 in CO2/HCO3(-)-buffered solution. In addition, the activity of this carrier, which is not affected either by decreasing Cai2+ or by inhibiting Ca2+/calmodulin protein kinase II, is down-regulated by inhibition of glycolysis. Under pathophysiological conditions such as diabetes, although total JHe was significantly decreased compared with normal myocytes, JHe carried by Na(+)-HCO3- cotransport remained unchanged. However, because of a decrease in Na+/H+ exchange, the contribution of this carrier to total JHe increased with decreasing pHi (i.e., under conditions that may be associated with an ischemic episode), reaching approximately 58% of total JHe at pHi 6.75 (vs. approximately 33% in normal myocytes.
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PMID:HCO3(-)-dependent alkalinizing transporter in adult rat ventricular myocytes: characterization and modulation. 943 92

In this study, we investigated the constrictor responsiveness to endothelin-1 (ET-1, 10-30 n m) of aortic rings (under 1 g resting tension in Krebs-Bicarbonate solution) from 8-weeks streptozotocin (STZ, 65 mg kg-1, i.p)-induced diabetic rats and vehicle-treated control rats. The maximum ET-1-induced contraction of the aorta in diabetic rats was increased by 150%, but the EC50 of ET-1 remained unchanged. Although in both groups, verapamil reduced the constrictor responses to ET-1 (diabetic group P<0.001, control group P<0.05), there were not any significant differences between PD2 values. These results suggest that verapamil inhibits ET-1-induced Ca2+ entry through the L-type channel and this effect did not change in diabetes mellitus.
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PMID:Effect of verapamil on responses to endothelin-1 in aortic rings from streptozotocin-induced diabetic rats. 1037 88

Acute magnesium (Mg) infusion decreases patathyroid hormone (PTH) secretion. However, the effect of chronic hypermagnesemia on PTH levels in dialysis patients is not well established. We studied 110 hemodialysis patients (mean age, 55 +/- 14 years; time on dialysis, 35 +/- 28 months) not receiving vitamin D and undergoing dialysis with an Mg dialysate concentration of 1.2 mg/dL. The primary phosphate binder was calcium carbonate, and 43% of the patients also needed aluminum hydroxide. During a 6-month period, calcium (Ca), phosphorus (P), and total serum Mg were measured every 2 months; intact PTH and aluminum (Al) were measured every 6 months. The mean value of each parameter was computed. Hypermagnesemia (serum Mg > 2.47 mg/dL) was observed in 73% of the patients. Mg and Ca were inversely correlated with PTH levels (r = -0.48; P < 0.001 and r = -0.21; P < 0.05, respectively). After adjusting for Ca and P (partial correlation analysis), Mg and PTH were inversely correlated (r = -0.58; P < 0.001). A stepwise multiple regression analysis showed that PTH levels were predicted by Mg (P < 0.001), alkaline phosphatase (P < 0.01), and P levels (P< 0.05; multiple R = 0.57; P < 0.001), whereas Ca level, sex (dummy variable), diabetes (dummy variable), time on dialysis, and Al level were not predictive. Patients with inadequately low PTH levels (relative hypoparathyroidism, PTH < 120 pg/mL; n = 52) showed greater serum Mg concentrations than the rest (n = 58; 3.01 +/- 0.33 v 2.63 +/- 0.38 mg/dL; P < 0.001). In conclusion, serum Mg concentrations in dialysis patients are independently associated with PTH levels, suggesting that chronic hypermagnesemia may decrease PTH secretion and/or synthesis. In addition, chronic hypermagnesemia of dialysis patients may have a role in the pathogenesis of adynamic bone disease.
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PMID:Relationship between serum magnesium and parathyroid hormone levels in hemodialysis patients. 1040 Oct 14

Recombinant human insulin-like growth factor-I (rhIGF-I) was found to improve glycemic control and enhance insulin sensitivity in patients with a syndrome of severe insulin resistance. Therefore, the protein may be considered as an alternative therapy in the treatment of diabetes when the patients become insensitive to insulin treatment. Because the protein was administered twice per day in the clinical trials, a sustained release polylactic-co-glycolic acid (PLGA) formulation for rhIGF-I with low initial burst (<20%), maximum possible protein loading (15-20%) and a continuous release of 1-2 weeks may provide greater patient convenience and compliance. The protein was encapsulated in PLGA for sustained release using a spray freeze-drying technique. Formulation parameters such as protein loading, polymer end group, and the presence of zinc carbonate were studied for their effects on in vitro release of rhIGF-I from PLGA microspheres. As the protein loading was increased, the initial burst increased. Due to the hydrophilic properties of the polymers, rhIGF-I encapsulated in unblocked PLGA (free acid end groups) gave a lower initial burst and a more steady-state release profile than the blocked PLGA (hydrocarbon end groups) with the same protein loading and PLGA molecular weight. At 15% w/w protein loading, the addition of 6% w/w zinc carbonate as a protein release modifier to the unblocked PLGA (12 kDa) decreased the initial burst of rhIGF-I. Therefore, a formulation consisting of 15% rhIGF-I and 6% zinc carbonate in 12 kDa, unblocked 50:50 PLGA can provide the required release characteristics in vitro. Rat studies revealed that rhIGF-I in this formulation was released in vivo at a rate which was comparable to that observed in vitro. These studies demonstrate the potential for a sustained release, 14-day formulation for rhIGF-I.
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PMID:Sustained release of recombinant human insulin-like growth factor-I for treatment of diabetes. 1082 61

Calcium supplementation is important in the treatment of osteoporosis, a disease that may also occur in diabetic patients. The acute effects of calcium supplementation and their relationship to gastric emptying time, however, have rarely been studied in type 2 diabetic patients. We evaluated the acute biochemical variations induced by the administration of two different calcium preparations, calcium citrate and calcium carbonate, in 16 (male/female: 13/3) Chinese diabetic patients. Serum free calcium, intact parathyroid hormone (i-PTH), and amount of urinary excretion of calcium (uCal/uCr) were evaluated after a single dose of 1200 mg of elemental calcium in each preparation. The free calcium levels did not change significantly in either group. However, significant suppression of i-PTH after calcium citrate administration at 1 h (17.1+/-2.0 pg/ml, P=.023), and after calcium carbonate administration at 2 h (14.2+/-2.5 pg/ml, P=.000), was noted when compared with individual basal level (21.2+/-2.5 and 19.3+/-2.4 pg/ml, respectively). The suppressive effect on i-PTH lasted for 6 h after calcium citrate and 5 h after calcium carbonate preparation of the 6-h study period. After administration of calcium citrate, the uCal/uCr of 2-to-4-h collection was significantly higher than that of the basal and 0-to-2-h collections: 0.25+/-0.04 vs. 0.19+/-0.03, P=.025; and 0.25+/-0.04 vs. 0.19+/-0.02, P=.014, respectively. A similar finding was observed for calcium carbonate: 0.23+/-0.03 vs. 0.18+/-0.02, P=.019; and 0.23+/-0.03 vs. 0.18+/-0.02, P=.011, respectively. We conclude that, in this group of Chinese type 2 diabetic patients in our study, the oral administration of 1200 mg elemental calcium in either calcium citrate or calcium carbonate preparation can induce a significant suppression of i-PTH. This may be helpful in preventing or treating osteoporosis. A prolonged gastric emptying time in these diabetic subjects may contribute to the non-significant alteration in free calcium levels after the administration of either calcium preparation.
J Diabetes Complications
PMID:Acute biochemical variations induced by calcium citrate and calcium carbonate in Type 2 diabetic patients: impaired calcium absorption in Type 2 diabetic patients with prolonged gastric emptying time. 1127 6

The aim of the study was to compare of nondominant forearm microcirculation in adult-type diabetes and healthy subjects with use of venous blood gasometry (vbg) sampled from basilic vein before and after exercise of antebrachial muscles and with use of laser doppler fluxometry (LDF) with optode localized in dorsal palm surface. Examinations were performed in groups of 16 diabetic patients (aged 43.5 +/- 5.7) and 16 healthy subjects (aged 39.3 +/- 7.8). After exercise of antebrachial muscles in diabetic patients in vbg were: pH higher, pO2 and satO2 lower than in healthy subjects, pCO2 and -HCO3 were not different in both group. In LDF in diabetic patients impaired hypraemic reaction, impaired heating to 40 degrees C reaction and hyperaemic reaction in this temperature were found.
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PMID:[Blood gas analysis of forearm veins--at rest and after exercise of forearm muscles and laser Doppler flowmetry of skin on the back of the palm--use in evaluation of microcirculation in diabetes type 2]. 1129 6

No intravenously injectable enzyme preparate containing urease as an alternetive to hemodialysis, hemoperfusion and CAPD systems in patients having chronic renal failure has been encountered in literature. In this study, it has been aimed to convert blood urea to alanine by using PEG-urease/PEG-AlaDH enzyme pair encapsulated within living erythrocyte. In this system, urea is decomposed into NH3 and HCO3- and the ammonia released is converted into alanine by reacting pyruvate under the catalytic action of alaninedehydrogenase. The production of pyruvate and NADH by erythrocyte required in the second stage of the reaction will make the process a feasible and ceaseless one. The success of the system will enable the renal patients with diabetes mellitus. Urease and AlaDH were covalently immobilized on activated PEG. PEG-urease/PEG-AlaDH were encapsulated in erythrocyte (1/1)(v/v) by using slow dialysis methods. The activity of enzyme system, encapsulation yield and hemogram analysis were determined for each sample.
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PMID:Encapsulation of PEG-urease/PEG-AlaDH enzyme system in erythrocyte. 1170 64


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