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)

1. This study investigated the responsiveness to vasoconstrictor agents (including endothelin-1, ET-1) of aortic rings from rats with two-week streptozotocin (STZ, 60 mg kg-1, i.v.)-induced diabetes and vehicle-treated control rats. The basal tension was 10 g, which was estimated to be more physiological than the tension of 1-2 g that has been previously used for most studies of aortic rings from diabetic rats. 2. Maximum responses to ET-1 (0.13-18 nM), KCl (2-20 mM) or CaCl2 (10 microM-10 mM) were reduced in aortae from STZ-treated rats compared to those from control rats. Such reductions were still evident after removal of the endothelium. 3. Responses to noradrenaline (NA, 0.1 nM-26 microM) of aortae from STZ-treated rats were not significantly different from responses of aortae of control rats. 4. Removal of endothelium resulted in a significant reduction in the EC50 values for NA of rings from both STZ-treated rats (6.90 +/- 0.13 and 8.17 +/- 0.35 (-log M) with and without endothelium, respectively, n = 5) and control rats (6.90 +/- 0.15 and 8.37 +/- 0.44 (-log M) with and without endothelium, respectively, n = 5). 5. In calcium-free medium (with 1 mM EGTA), responses to NA and ET-1 were reduced compared with those in normal Krebs solution and maximum responses were less in rings from STZ-treated compared with control rats. 6. Indomethacin (5 microM) did not prevent the reduced maximum responsiveness to ET-1 in rings from STZ-treated rats compared with those from controls.7. This study indicates that changes in vascular responsiveness to ET-1, KCI and CaCl2 (but not NA) occur in aortae of two-week STZ-treated rats. The endothelium does not appear to play a major role in mediating changes in responsiveness to ET-1.
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PMID:Attenuated responses to endothelin-1, KCl and CaCl2, but not noradrenaline, of aortae from rats with streptozotocin-induced diabetes mellitus. 181 Jun 3

We investigated the effect of alginate-polylysine-alginate microencapsulation on glucose-induced insulin secretion by rat islets. Applying the encapsulation method originally described by Lim, we found severely reduced in vitro insulin release (expressed as picomoles of insulin.10 islets-1.45 min-1 when incubated in 16.5 mM glucose), because the insulin release with encapsulated islets was 1.42 +/- 0.49 compared to 13.58 +/- 0.80 with free control islets. This could not be explained by inadequate permeability of the capsule, because insulin release was also severely reduced (2.12 +/- 0.61) when islets were subjected to the procedure but without the membrane-forming polylysine step. Therefore, islets were tested after having been subjected separately to each of the steps of the procedure. Insulin release was not affected by either alginate or CaCl2 but was severely reduced after prolonged suspension in saline or treatment with citrate. When saline and citrate were replaced by Ca2(+)-free Krebs-Ringer bicarbonate buffer (KRBB) and 1 mM EGTA, respectively, insulin release improved significantly both with complete and with incomplete (no polylysine step) encapsulation. This outcome was verified in a set of experiments run in parallel with islets derived from the same isolation procedure. Insulin release was 1.20 +/- 0.23 from islets encapsulated with the method of Lim and 10.73 +/- 1.04 from free control islets. With the modified procedure, insulin release was 9.17 +/- 0.52 vs. 9.61 +/- 1.27 for complete versus incomplete encapsulation, respectively. We conclude that Ca2(+)-free KRBB instead of saline and EGTA instead of citrate should be used to obtain an adequate insulin response from encapsulated islets and that the capsule membrane as such has no influence on glucose and insulin diffusion.
Diabetes 1991 Jan
PMID:Effect of alginate-polylysine-alginate microencapsulation on in vitro insulin release from rat pancreatic islets. 201 72

It is a well known fact that isolated, energized mitochondria take up large amounts of Ca2+, thus regulating their own internal Ca2+ concentration and modulating the activity of matrix dehydrogenases involved in the aerobic steps of glucose oxidation. The information available on biochemical alterations in diabetes is extensive but no data on Ca2+ transport alterations have been reported. Therefore, it seemed of interest to study Ca2+ uptake and release (efflux) by liver mitochondria of diabetic rats, in relation to other metabolic parameters representing the energization state of the inner mitochondrial membrane. Rats (male; 200 +/- 20 g body weight) were injected with streptozotocin (65 mg/kg) and after 1-3 months, liver mitochondria were isolated and suspended in an isotonic medium supplemented with 3.0 microM rotenon, 5.0 mM succinate (the energy source), 50 microM Antipyrylazo III and CaCl2 (20-100 microM Ca2+). Ca2+ uptake was monitored by the decrease of the Ca2(+)-Antipyrylazo III complex concentration, measured spectrophotometrically at 720-790 nm and 30 degrees C. The initial rates of Ca2+ uptake (in nmol Ca2+/min/mg of protein; average +/- S.E., n = 5) were as follows (in parenthesis, initial [Ca2+] microM): normal mitochondria, 171 +/- 20 (20); 207 +/- 13 (40); 233 +/- 22 (60) and 237 +/- 14 (100); diabetic mitochondria, 114 +/- 13; 134 +/- 22; 186 +/- 7 and 184 +/- 14, respectively. Accordingly, the decrease of Ca2+ uptake activity was 33, 36, 20 and 22 (%), respectively (P less than 0.05 at all [Ca2+].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Diabetes and calcium transportation in liver mitochondria]. 263 Aug 70

To examine the myocardial contractile response of the diabetic heart, effects of isoproterenol (ISO) and norepinephrine (NE) on perfused hearts isolated from streptozotocin (STZ)-induced diabetic rats and insulin-treated diabetic rats were evaluated. Male Sprague-Dawley rats, weighing 200-260 g, were divided into the control (C)-group, diabetes mellitus (DM)-group and diabetes mellitus treated with insulin (DMI)-group. The C group was injected with buffered vehicle. DM and DMI groups were injected intravenously with 60 mg/kg STZ on the first day. Three days after STZ injection, the DMI group was subsequently treated with 4 U of Lente insulin subcutaneously every day. At 45 days after injection of STZ, experiments were performed using a Langendorff perfused heart preparation. The heart was paced at 300 beats/min, and myocardial developed tension (T) was measured isometrically. Plasma glucose values (mg/dl) were 142.4 +/- 8.7 in C, 499.3 +/- 15.6 in DM and 370.6 +/- 27.6 in DMI group. The order of percent increase in T induced by ISO (3 X 10(-9) - 3 X 10(-8) g) was C = DMI much greater than DM, and that by NE (10(-7) - 10(-6) g) was C greater than DMI greater than DM. On the other hand, the percent increase in T induced by CaCl2 (1.1 X 10(-4) - 2.2 X 10(-3) g) and aminophylline (AMI, 0.31 X 10(-3) - 5.00 X 10(-3) g) was not significantly different among three groups. These results indicate that adrenergic receptor-mediated contractile response was significantly depressed in the diabetic heart.
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PMID:Effects of adrenergic drugs on isolated and perfused hearts of streptozotocin-induced diabetic rats. 330 14

Rat pancreatic islets contain an ionized or readily ionizable calcium fraction that can be determined by the metallochromic indicator glyoxal-bis-(2- hydroxyanil ) ( GBHA ). This calcium fraction is mainly localized in the secretory granules. The relationship between the effects of glucose on 45Ca uptake and on this ionized calcium fraction was investigated. In addition, the effects of glucose on total islet calcium content were also studied. Stimulation of isolated islets for 30 min with 15 mM glucose in the presence of 2.5 mM CaCl2 increased the 45Ca uptake but decreased the GBHA -Ca content, while the total calcium content was not affected. Deletion of CaCl2 caused, at 2.5 mM glucose, an abrupt decrease of GBHA -Ca, which did not occur at 15 mM glucose. Total islet calcium content decreased slowly at 2.5 mM glucose, but this was not significantly affected by glucose stimulation. Islet GBHA -Ca can be reduced by 70% and total islet calcium by 30% by means of washing with calcium-free buffer. Reintroduction of calcium at 2.5 mM glucose partly restored, but glucose 15 mM completely restored, the GBHA -Ca level within 5 min. The total calcium content was restored within 15 min independent of the glucose concentration. The increase of the islet calcium content equalled the 45Ca uptake at 2.5 mM glucose. The 45Ca uptake at 15 mM glucose was higher than the increase of the islet calcium content. The results indicate that the intragranular Ca2+ pool, as measured by GBHA , is rapidly and dramatically altered by glucose stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 May
PMID:Glucose-induced changes in histochemically determined Ca2+ in B-cell granules, 45Ca uptake, and total Ca2+ of rat pancreatic islets. 637 49

It has been generally accepted that acidosis results in hyperkalemia because of shifts of potassium from the intracellular to the extracellular compartment. There is ample clinical and experimental evidence, however, to support the conclusion that uncomplicated organic acidemias do not produce hyperkalemia. In acidosis associated with mineral acids (respiratory acidosis, end-stage uremic acidosis, NH4Cl-or CaCl2-induced acidosis), acidemia per se, results in predictable increases in serum potassium concentration. In acidosis associated with nonmineral organic acids (diabetic and alcoholic acidosis, lactic acidosis, methanol and the less common forms of organic acidemias secondary to methylmalonic and isovaleric acids, and ethylene glycol, paraldehyde and salicylate intoxications), serum potassium concentration usually remains within the normal range in uncomplicated cases. A number of factors, however, may be responsible for hyperkalemia in some of these patients other than the acidemia per se. These include dehydration and renal hypoperfusion, preexisting renal disease, hypercatabolism, diabetes mellitus, hypoaldosteronism, the status of potassium balance, and therapy. The mechanism(s) of this differing effect of mineral and organic acidemias on transmembrane movement of potassium remains undefined. The prevalent hypothesis, however, favors the free penetrance of the organic anion into cells without creating a gradient for the hydrogen ions and, thus, obviating the efflux of intracellular potassium. The importance of the presence of hyperkalemia in clinical states of organic acidemias is obvious. A search for the complicating factors reviewed above should be undertaken since organic acidemias per se, should not be expected to be accompanied by elevations of serum potassium concentration. Moreover, the classical teaching that the absence of hyperkalemia during severe acidosis is indicative of severe potassium deficiency, may not be universally valid in patients with uncomplicated organic acidemias.
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PMID:Serum potassium concentration in acidemic states. 679 Oct 40

Responses of isolated aorta and portal vein (PV) to norepinephrine (NE), angiotensin II (AII), KCl, and CaCl2 were investigated in alloxan diabetic rats. Based on serum biochemical parameters (i.e., glucose, cholesterol, triglycerides, and creatinine) (alloxan, 150 mg/kg), diabetic rates were divided into three groups: 1) mildly diabetic at 1 week (only elevated glucose levels), 2) moderately diabetic at 4 wk (elevated glucose, triglycerides, and creatinine), and 3) severely diabetic at 8 wk (all serum biochemical parameters elevated). The sensitivity (i.e., ED50) of aortic smooth muscle from diabetic rats when compared to saline controls was 1) unchanged in mild diabetes; 2) decreased to KCl, AII, and CaCl2 in moderate diabetes; and 3) decreased to KCl, NE, and CaCl2 in severe diabetes. Ability of aortic smooth muscle to develop maximal contractions (i.e., contractility) to all these agonists was markedly diminished in severe diabetes. Spontaneous phasic contractions of PV from diabetic rats exhibited progressively greater tension as the disease advanced. Unlike aortas, contractility of PV to vasoactive agents was not affected at any stage of diabetes. PV sensitivity to AII in moderate diabetes and to Ca in severe diabetes was decreased when compared to saline controls. These differences in reactivity and contractility of aorta and PV in progressive stages of experimental diabetes could be due to alterations in calcium handling and its metabolism in arterial and venous smooth muscle cells in the diabetic state.
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PMID:Vascular responsiveness and serum biochemical parameters in alloxan diabetes mellitus. 744 23

Sodium-potassium ATPase activity and transmembrane calcium influx in the aortic smooth muscle from control and diabetic rats were assessed indirectly through the measurement of KCl relaxation and contractile responses to CaCl2 in attempts to explain the contractile responses to KCl following streptozotocin-induced diabetes mellitus. There were no significant changes in the maximum contractile responses of the aortas from 4 and 12 week diabetic rats to KCl even when significant increases in calcium influx were demonstratable. On the other hand, the diabetic aortas were significantly (P < 0.05) more sensitive to KCl-induced relaxations than the controls. This provides an indirect evidence for increased activity of the sodium-postassium ATPase enzyme in the aortas from streptozotocin diabetic rats. This may, atleast in part, explain the inability of KCl to produce greater than normal contractions of the aortas from diabetic rats.
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PMID:Enhanced Na-K ATPase activity in the aorta may explain the unaltered contractile responses to KCl in diabetes mellitus. 827 95

In order to gain a better understanding of the kinetics of activation and inhibition of hepatic monoacylglycerol acyltransferase (MGAT) (EC 2.3.1.22) by fatty acid, we examined the effect of fatty acid with respect to MGAT's long-chain acyl-CoA substrate in Triton X-100 mixed micelles. At concentrations between 2.5 and 5.3 mol %, oleic acid stimulated MGAT activity 2-fold, whereas oleic acid inhibited MGAT at concentrations higher than 7.5 mol %. The dependence on palmitoyl-CoA was highly cooperative with a Hill constant of greater than 2.4. When present at less than 3 mol%, oleic acid eliminated the lag in the dependence curve. When concentrations of oleic acid were higher than 3 mol %, Michaelis-Menton kinetics were observed with an apparent k(m) value of about 54 microM for palmitoyl-CoA but with progressively decreasing Vmax values. This effect was not observed with octanoic acid, suggesting that the medium-chain fatty acid is unable to associate stably with the mixed micelle and, thus, cannot substantially alter substrate affinity. When anionic phospholipids were tested, phosphatidic acid, lysophosphatidic acid, phosphatidylserine, and phosphatidylinositol eliminated some of the lag in activation by palmitoyl-CoA. At high molar concentrations of the anionic lipid activators, apparent k(m) values ranged from 77 microM for phosphatidic acid to 196 microM for phosphatidylinositol. Zwitterionic phospholipids had no effect, nor did the non-phospholipid activators bovine serum albumin or sn-1,2-diacylglycerol. CaCl2, but not neomycin or KC1, could overcome the inhibitory effect of oleic acid; thus, the inhibitory effect of fatty acid did not appear to occur by electrostatic interactions. These blockers did not change the effects observed with the anionic phospholipid activators or with the inhibitor, sphingosine. An altered k(m) for palmitoyl-CoA in the presence of fatty acid or anionic phospholipid suggests that both long-chain fatty acids and phospholipid cofactors may induce a conformational change in MGAT, thereby altering the enzyme's affinity for its long-chain acyl-CoA substrate. These data further support the hypothesis that the synthesis of glycerolipids via the monoacylglycerol pathway may be highly regulated via a variety of lipid second messengers such as phosphatidic acid and diacylglycerol, as well as by the influx of fatty acids derived from high-fat diets, or from the hydrolysis of adipocyte triacylglycerol during fasting or diabetes.
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PMID:Fatty acids and anionic phospholipids alter the palmitoyl coenzyme A kinetics of hepatic monoacylglycerol acyltransferase in Triton X-100 mixed micelles. 875 39

A capillary zone electrophoresis method was optimised to analyse low-molecular-mass organic acids for the purpose of monitoring diabetes in rat plasma. The method included acetoacetic, 2-hydroxybutyric, lactic and uric acids. A variation in the background electrolyte allowed us to measure pyruvic acid in the same sample. Conditions have been optimised for measuring a large number of plasma samples corresponding to control and diabetic rats. Samples were mixed with acetonitrile (1:1, v/v) to precipitate proteins, centrifuged, diluted and injected. Tropic acid was chosen as an adequate internal standard. Separation was developed with reversed voltage by using a column cartridge pre-treated with polyacrylamide. Two electrophoretic buffers were employed: 0.150 M H3PO4 made up pH 6.20 with NaOH and 0.3 mM CaCl2 for acetoacetic, hydroxybutyric, lactic and uric acids, and 200 mM phosphate-10 mM acetate pH 4.0 for pyruvic acid, both with direct detection at 200 nm. The method was validated for linearity, accuracy and precision and the limits of quantification were calculated. The method was successfully applied to analyse these organic acids in control and diabetic animals. Acetoacetic and hydroxybutyric acids were clearly increased in diabetic rats, meanwhile no statistically significant difference has been found with the other acids.
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PMID:Evaluation of diabetes-related short-chain organic acids in rat plasma by capillary electrophoresis. 1553 74


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