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

In the present study fast axonal transport was examined in streptozotocin rats with 4 weeks duration in diabetes. Tritiated leucine and 14C-labelled glucosamine were injected into the fifth lumbar ganglion and TCA-soluble as well as insoluble activity were measured in segments of the sciatic nerve at various time intervals. (1) Time from injection until start of fast axonal transport was prolonged in diabetic rats whereas anterograde transport velocity was unchanged. (2) Incorporation of labelled leucine was reduced by 40%, whereas labelled glucosamine incorporation was unchanged. (3) Alterations observed in accumulations of labelled glycoconjugates proximal and distal to a collection crush might represent a decreased amount of retrograde transported material. The changes found in protein and glycoconjugate synthesis and transport could be related to the early reduction in axon calibre and conduction velocity in peripheral nerve of streptozotocin-diabetic rat.
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PMID:Axonal transport in early experimental diabetes. 9 May 40

Diabetes stimulates the functional activity of the intestinal brush border membrane with enhancement of both hydrolytic enzyme activity and membrane transport systems. To determine the mechanism of this effect, we studied the effects of streptozotocin diabetes on the metabolism of one membrane protein, sucrase-isomaltase, which increases its activity in diabetes. The protein was purified and an antiserum prepared. Sucrase-isomaltase from control and diabetic rats was immunologically identical as shown by Ouchterlony double-diffusion analysis of papain-solubilized mucosal proteins. The increase in sucrase enzyme activity in diabetic animals (31.0+/-1.4 U SEM 5 days after streptozotocin vs. 13.1+/-1.0 in controls) was the consequence of increased enzyme protein and not an alteration in catalytic efficiency as demonstrated by quantitative immunoprecipitin reactions. To account for increased sucrase-isomaltase protein in diabetes we studied papain-solubilized mucosal proteins labeled by injection of [(14)C]carbonate and [(14)C]leucine and analyzed incorporation into sucrase-isomaltase protein (anti-serum precipitable) and total protein (trichloroacetic acid precipitable). We found that diabetes did not affect the decay of labeled total protein, but prolonged the decay of labeled sucrase-isomaltase. t((1/2)) of sucrase-isomaltase was 4.4 h in control animals after [(14)C]carbonate injection and 8.8 and 10.2 h, respectively, 2 and 5 days after induction of streptozotocin diabetes. We obtained similar results in experiments with [(14)C]leucine with diabetes increasing t((1/2)) from 6 to 13.6 h. Diabetes did not appear to increase the rate of addition of sucrase-isomaltase to the brush border membrane, since it did not affect the 10- and 60-min incorporations of isotope into sucrase-isomaltase protein relative to incorporation into total protein and did not alter rate constants for synthesis calculated from the t((1/2)) and the change in enzyme mass over time.Thus, enhanced sucrase activity in the diabetic animal is the consequence of an increase in sucrase-isomaltase protein which develops because of a decrease in its rate of degradation.
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PMID:The intestinal brush border membrane in diabetes. Studies of sucrase-isomaltase metabolism in rats with streptozotocin diabetes. 14 62

Recently, evidence has been reported to suggest that human platelets like several other circulating blood cells may bind insulin. To examine whether human platelets contain specific insulin receptors, washed human platelets suspended in Hepes buffer were incubated at 24 degrees C with 125I-insulin in the presence and absence of unlabeled insulin and specific insulin binding was determined. Insulin binding by platelets increased progressively with time of incubation to reach a maximum at 3 h and was proportional to the number of platelets in the incubation mixture. Maximum insulin binding was observed at pH 8. Insulin degradation by platelets as assessed by TCA precipitability and reincubation studies was minimal. Scatchard analysis of the binding data and dissociation studies revealed evidence of negative cooperativity of the platelet insulin receptor. A high affinity dissociation constant of approximately equal to 3 X 10(9) M-1 was determined and the concentration of platelet insulin receptors was estimated as 25 binding sites/micron2 platelet surface area. Binding of 125I-insulin by platelets was inhibited by unlabeled porcine insulin and to a lesser extent by catfish insulin and porcine proinsulin but not by glucagon, prolactin, growth hormone, and thrombin. The findings indicate that human platelets contain specific insulin receptors. The significance of the platelet insulin receptor, particularly with respect to altered platelet function in diabetes mellitus, remains to be determined.
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PMID:Demonstration and partial characterization of insulin receptors in human platelets. 44 28

Higher omega-oxidation activities in the diabetic mammal and the starved one suggest that omega-oxidation mechanism plays an important role under these conditions. Dicarboxylic acid that is the final product of omega-oxidation can be metabolized further by beta-oxidation, subsequently, formation of succinyl-CoA and short-chain dicarboxylic acid might be increased in the liver. The physiological significance of omega-oxidation might consist in supplying the substrate of TCA cycle for utilization of acetyl-CoA and excreting the short-chain dicarboxylate in urine resulting in the decrease of ketone bodies in the blood, especially in diabetes and starvation. On the bases of these information, it is important to investigate the metabolism of dicarboxylic acids. Generally, fatty acids must be activated before they enter the metabolic pathway. By in vitro studies with rat liver homogenate, we have recently demonstrated that octadecaned-ioic acid must be activated by ATP-Mg2+ and CoA as monocarboxylic acid is. However, it has not been studied to compare the activity of acyl-CoA synthetase on mono and dicarboxylic acid. So, in this report, we assayed the activity of acyl-CoA synthetase in beef liver preparations using palmitic or hexadecanedioic acid (C1;16) as substrate. The results are as follows 1) Activation capacity of the supernatant of sonicated mitochondria was less than that of sonicated microsome for either palmitate or hexadecanedioate. 2) Activation capacity for hexadecanedioate was less than that for palmitate in both supernatant of sonicated mitochondria and that of sonicated microsome. 3) In our experiment, it might be suggested that the subcellular distribution of hexadecanedioate activation is almost identical with that of palmitate activation.
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PMID:[Acyl-CoA synthetase activity of long-chain mono and dicarboxylic acid in beef liver preparations (author's transl)]. 94 21

PGE1 has been found to improve the symptoms of diabetic neuropathy. We considered that a PGI2 derivative may also have a similar action and therefore studied its effect in diabetic rats. Iloprost was administered intraperitoneally to streptozotocin-induced diabetic rats at a dose of 10 micrograms/kg/day for a month. The changes in nerve conduction velocity (NCV) were measured in the tail. One day after the last dose of iloprost, both sciatic nerves were removed from each rat, homogenized, and extracted with 6% TCA. The sorbitol and myo-inositol concentrations were determined by a combination of HPLC and an enzymatic method. Cyclic AMP (cAMP) levels were determined by RIA, and Na+, K+ ATPase activity was assessed by the enzyme cycling method of Greene and Lattimer. Iloprost was found to improve the NCV in the diabetic rats. The sorbitol content was not affected by iloprost, but the myo-inositol content was higher in the iloprost group than in the untreated group, although the difference was not statistically significant. The Na+, K+ ATPase activity and cAMP content were significantly higher in the iloprost group than in the untreated group. These findings suggest the possibility that the cAMP-dependent protein kinase (A-kinase) system has an important influence on improvement in Na+, K+ ATPase activity.
Diabetes Res Clin Pract 1992 Nov
PMID:Effect of a prostaglandin I2 derivative (iloprost) on peripheral neuropathy of diabetic rats. 128 52

A competitive radioimmunoassay for the quantitative determination of glycated haemoglobin was developed. The antiserum, obtained by immunizing guinea pigs with reduced glycated human albumin, was capable of identifying and quantitating the glucitollysine residues of glycated Hb after reduction with sodium borohydride. To simplify the sample preparation we introduced trichloroacetic acid precipitation to remove unreacted sodium borohydride instead of using dialysis or gel filtration. Using this procedure, our radioimmunoassay became relatively simple and provided satisfactory within- and between-run (1.3-2.8% and 1.9-5.4% coefficient of variation, respectively). The radioimmunoassay method was compared to the measurement of HbAlc by high performance liquid chromatography which is the most widely used method for quantitating glycated Hb. For this purpose glycated Hb was measured in normal glucose tolerance, impaired glucose tolerance, and diabetes mellitus groups based on WHO criteria. Both assays were able to discriminate between the normal and diabetic groups. In addition, while the determination of glycated Hb by the radioimmunoassay method was able to clearly discriminate between the normal and impaired glucose tolerance groups, the determination of HbAlc by the high performance liquid chromatography method failed to discriminate between these two groups. Moreover, 15 of the 20 impaired glucose tolerance patients exceeded the upper normal range (mean normal values + 2 SD) in radioimmunoassay. But all 20 patients with impaired glucose tolerance were within the upper normal range in HbAlc values. These results demonstrate that the measurement of glycated Hb by radioimmunoassay is more sensitive than the measurement of HbAlc by high performance liquid chromatography since it can discriminate between the normal and impaired glucose tolerance groups.
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PMID:Radioimmunoassay for the determination of glycated haemoglobin. 190 46

Insulin deficiency leads to a decreased ability of cholecystokinin octapeptide (CCK-8) to raise cytosolic free-calcium levels in the pancreatic acinar cell. To elucidate the mechanisms underlying this defect, we studied the effects of CCK-8 on phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis in pancreatic acini prepared from nondiabetic and streptozocin-induced diabetic rats. Analysis by high-pressure liquid chromatography indicated that, in diabetic rat acini, the CCK-8-mediated increase in [3H]inositol 1,4,5-trisphosphate ([3H]IP3) levels was delayed, and the increase in [3H]inositol 1,3,4,5-tetrakisphosphate ([3H]IP4) levels was markedly attenuated compared with nondiabetic rat acini. The expected increase in the mass levels of IP3, measured in a competitive binding assay, was reduced in the diabetic group after incubation with CCK-8, carbachol, and bombesin. Phospholipase C activity was decreased by 30% in diabetic rat acini, whereas the specific activity of PIP2 and the amount of myo-[3H]inositol in the free and trichloroacetic acid-precipitable pools were similar in both groups. The nonhydrolyzable analogue of GTP guanosine-5'-O-(3'-thiotriphosphate) rapidly enhanced IP3 levels in permeabilized acini, and the percent increase above basal was greater in the diabetic group. When added for 5 s or 2 h, insulin did not alter basal or CCK-8-stimulated [3H]IP3 and [3H]IP4 levels in either nondiabetic or diabetic rat acini. However, after a 4-h incubation, insulin increased basal [3H]IP3 and [3H]IP4 levels in diabetic rat acini and potentiated the actions of CCK-8 on both inositol phosphates. Insulinlike growth factor I did not alter [3H]IP3 and [3H]IP4 levels either acutely or after a 4-h incubation. These findings point to a defect in the signal-transduction pathway that is activated by CCK-8 and other calcium-mobilizing agonists in the diabetic rat pancreas and suggest that insulin, acting via its own receptor, exerts long-term regulatory effects on PIP2 hydrolysis in the pancreatic acinar cell.
Diabetes 1991 Oct
PMID:Alteration of cholecystokinin-mediated phosphatidylinositol hydrolysis in pancreatic acini from insulin-deficient rats. Evidence for defective G protein activation. 193 91

Hemoglobin A1c was studied by means of isoelectric focusing in borate-polyol system and modified albumin--using electrophoresis of blood serum on acetate-cellulose films with subsequent TCA-ethanol sedimentation in healthy volunteers and patients with diabetes mellitus. These parameters were increased in the patients, whereas content of the albumin was decreased and the content of hemoglobin A1c was altered only slightly during treatment of diabetes. Content of hemoglobin A1c and modified albumin was shown to depend on the compensation state of diabetes mellitus.
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PMID:[Level of hemoglobin A1c and modified blood serum albumin in patients with diabetes mellitus]. 194 83

To describe quantitatively the in vivo distribution and elimination of insulin, high-performance liquid chromatography (HPLC) separation was applied to the pharmacokinetic study of human insulin labeled with 125I at tyrosine A14 (A14-125I-insulin) as a tracer. Intact A14-125I-insulin levels were determined by HPLC and trichloroacetic acid (TCA) precipitation in plasma and various tissues after its intravenous bolus injection into mice. TCA precipitation consistently overestimated the intactness of A14-125I-insulin compared with HPLC, possibly due to the presence of both a TCA-precipitable intermediate degradation product of labeled insulin found in HPLC elution profiles and reported high-molecular-weight forms of labeled insulin in plasma. Thus, TCA precipitation gave a considerably lower total plasma clearance (Cltot) value than HPLC. The half-life of A14-125I-insulin was prolonged by a simultaneous injection of 8 U/kg unlabeled insulin, and labeled insulin behaved similarly to [14C]inulin (an extracellular fluid marker). The concentration time profiles of HPLC-separated labeled insulin in plasma were analyzed by a noncompartmental moment method, and both Cltot and steady-state apparent volume distribution (VDss) of A14-125I-insulin were considerably decreased by unlabeled insulin coadministration. In particular, VDss of labeled insulin decreased by 79%, similar to that of inulin (181 ml/kg), suggesting that the nonspecific binding of labeled insulin to tissues was so small that VDss of labeled insulin was reduced to the extracellular fluid volume (approximately 20% of the body weight) when its receptor binding was blocked effectively by unlabeled insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 May
PMID:Application of HPLC in disposition study of A14-125I-labeled insulin in mice. 218 7

In an earlier study, we described the presence of a retroendocytotic pathway for insulin in a cultured kidney epithelial cell line. Derived from the opossum kidney (OK), these cells possess many features of proximal tubule epithelium, which is the major site of kidney insulin metabolism. We studied the interaction between the retroendocytotic and the degradative pathways with bacitracin as a pharmacological probe. Monolayers of OK cells were loaded with 125I-labeled insulin over 30 min, acid washed to remove membrane-bound insulin, then incubated in fresh medium for 60 min while the release of intracellular radioactivity was monitored. In experiments carried out in the presence of bacitracin (2 mM), there was a two-thirds increase in intracellular radioactivity at the end of the loading phase. Measurements made during the subsequent release phase showed that bacitracin reduced the release of degradation products. Thus, although controls released 72.1 +/- 8.1% of the internalized radioactivity as trichloroacetic acid (TCA)-soluble products, bacitracin-treated cells released 59.2 +/- 9.4% (P less than 0.02). In contrast, release of TCA-precipitable insulin increased from 15.2 +/- 4.6% in controls to 25.8 +/- 3.7% in bacitracin-treated cells (P less than 0.01). In separate experiments analyzed by gel-exclusion chromatography, 6.4 +/- 0.6% of radioactivity released from preloaded control cells into medium over 60 min was insulin sized compared to 29.7 +/- 1.4% in bacitracin-treated cells. High-performance liquid chromatography revealed that 61.5 +/- 3.5% of this insulin-sized material released from control cells preloaded with A14-insulin eluted as intact insulin and the remainder as unidentified intermediate degradation products.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Nov
PMID:Effect of bacitracin on retroendocytosis and degradation of insulin in cultured kidney epithelial cell line. 222 8


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