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)

Patients with diabetes may have peripheral neuropathy, which may have clinical implications for the use of regional nerve block. The effects of local anesthetics on nerve conduction and nerve fiber injury were tested in control rats and at 4 weeks after the onset of diabetes in rats injected with streptozotocin (50 mg/kg intraperitoneally). Nerve conduction was assessed by recording evoked electrical activity in hindpaw muscles following ipsilateral electrical stimulation of the sciatic nerve near the hip. Block of motor nerve conduction was quantified by recording the amplitude of the evoked response at 1-min intervals for up to 15 min after the injection of 500 microliters 1% lidocaine HCl or procaine HCl into the midthigh next to the sciatic nerve. In control animals, procaine was much less effective than lidocaine in producing conduction block. The rate and magnitude of lidocaine-induced conduction block were not significantly different between control and diabetic groups. However, conduction block due to procaine was sufficiently enhanced in diabetic rats to become comparable to that of lidocaine-treated control nerves. Long-lasting injury was assessed in sciatic nerve harvested 2 days after the extraneural injection of saline or 2 or 4% lidocaine HCl. Using a light microscope with a superimposed grid, nerve edema was quantified as the proportion of intersection points falling on extracellular space. Lidocaine induced edema in both control and diabetic nerves, but 4% lidocaine induced significantly more edema in diabetic nerves than in controls. Nerve fiber injury, based on light microscopic scoring of axonal degeneration and demyelination, was not observed in saline-treated nerves.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Local anesthetic-induced conduction block and nerve fiber injury in streptozotocin-diabetic rats. 846 86

Aminoguanidine-HCl inhibits the formation of advanced glycosylation end products (AGEs) in vitro and in vivo, but the mechanism by which this occurs has not been determined. Aminoguanidine inhibited glucose-derived AGE formation on RNase A by 67-85% at aminoguanidine-glucose molar ratios of 1:5 to 1:50 without affecting the concentration of Amadori products. Fast-atom-bombardment mass spectrometry of RNase peptides incubated with glucose alone or with glucose plus aminoguanidine showed that aminoguanidine inhibited the formation of AGEs without forming an adduct with glycosylated peptide. These data suggest that the primary mechanism of aminoguanidine action is reaction with Amadori-derived fragmentation products in solution. These findings are relevant to the potential clinical use of aminoguanidine in the prevention of diabetic complications.
Diabetes 1992 Jan
PMID:Mechanistic studies of advanced glycosylation end product inhibition by aminoguanidine. 172 35

Costal cartilage from experimentally diabetic rats, labeled in vivo or in vitro with [35S]sulfate, was shown to incorporate less label into proteoglycans than cartilage from nondiabetic rats. Analyses of guanidine HCl cartilage extracts by gel chromatography on Sepharose CL-2B showed two major peaks at Kav approximately 0.4 and 0.8 (peaks I and II, respectively). Cartilage extracts from the diabetic rats contained predominantly peak II proteoglycans, while 60 and 55%, respectively, of the total 35S-labeled proteoglycans extracted from control cartilage labeled in vivo and in vitro with [35S]sulfate were present in peak I. After insulin treatment of the diabetic rats, the relative amount of peak I 35S-labeled proteoglycans synthesized in vivo was increased to 70%. The overall in vivo incorporation of [35S]sulfate into proteoglycans was also stimulated in diabetic rats treated with insulin to levels above those found for control rats. Thus, diabetes-induced changes in the biosynthesis of rat costal cartilage proteoglycans may be alleviated by normalization of the diabetic state by insulin treatment. However, addition of insulin (10(-5)-10(-9) M) to the culture medium did not affect the amount of 35S-labeled proteoglycans synthesized in vitro or the relative amounts of peak I proteoglycans produced by control or diabetic cartilage, suggesting that insulin does not have a direct effect on proteoglycan production. Moreover, no decrease in the amount of 35S-labeled proteoglycans produced was found when glucose at high concentrations was present in the culture medium. However, the presence of rat serum resulted in an increase in the amount of 35S-labeled proteoglycans produced by both control and diabetic cartilage, demonstrating that the cartilage explants were metabolically responsive to stimulatory factors.
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PMID:Effect of insulin on the altered production of proteoglycans in rib cartilage of experimentally diabetic rats. 189 27

The measurement of serum insulin-like growth factors (IGFs) in serum is complicated by the presence of high affinity IGF-binding proteins. The accurate measurement of IGFs by radioligand binding assays requires that the interference from binding proteins be eliminated. Acid-gel chromatography, the standard method for removing binding proteins, is laborious and time consuming. Alternative methods for extracting serum IGFs include the use of HCl-ethanol treatment and reverse phase minicolumns. However, these methods are unsuitable for use with serum for some species, such as rat and sheep, due to incomplete removal of binding proteins. We developed a fast protein liquid chromatography size-exclusion chromatographic method for characterizing the presence of IGF-binding proteins in physiological fluids and used this method to systematically investigate different combinations of acids and organic solvents as potential extraction methods for IGFs. We developed and validated an improved extraction procedure that uses formic acid, Tween-20, and acetone. The new extraction method was used in conjunction with purified biosynthetic human IGF-II and a commercially available anti-IGF-II monoclonal antibody in the development of an improved RIA for IGF-II. The new RIA is sensitive (5.0 pg/tube), specific (IGF-I cross-reactivity, less than 1%), and reproducible [interassay precision (coefficient of variation), less than 9.2%). We measured the serum concentrations of IGF-II in adults and found a significant difference between normal subjects and individuals with insulin-dependent diabetes mellitus.
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PMID:Measurement of insulin-like growth factor-II in physiological fluids and tissues. I. An improved extraction procedure and radioimmunoassay for human and rat fluids. 198 63

Diabetes in the mother may cause disturbances in the chondrocyte development in the embryo. A rat model was used to investigate whether this was reflected in the production of proteoglycans by cells from two embryonic regions. One of these regions is resistant (limb bud) and the other susceptible (mandibular arch) to malformation in diabetic pregnancy. Chondroitin sulphate proteoglycans from cultures of day-12 rat embryo limb bud and mandibular arch chondrocytes were extracted with guanidine-HCl and analyzed by gel chromatography after in vitro 35S-sulphate-labeling. Two sizes of proteoglycans (Kav 0.26 and 0.66 on CL-2B Sepharose) were found in both types of chondrocytes and in all media. The polysaccharide chain length was the same (Kav 0.36 on CL-6B Sepharose) for both proteoglycans. Elevated levels of D-glucose or beta-hydroxybutyric acid had no effect on either proteoglycan size or proportion, nor on polysaccharide chain length. However, there were differences (in all culture conditions) between limb bud and mandibular arch cultures in that the larger proteoglycan accounted for 80% of total radioactivity in the limb bud cultures, 53% in the mandibular arch cultures, and only 25-29% in the media from both types of cultures. Furthermore, different ratios between radioactive proteoglycans in medium and matrix suggested markedly different efficiencies for matrix formation in the two cell types. These findings indicate differences in the metabolism of the proteoglycans in these two cell types which may be related to the induction of mandibular malformation in diabetic pregnancy.
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PMID:Metabolism in vitro of cartilage proteoglycans in rat (pre)chondrocytes from different embryonic regions. 221 60

A significant segment of the Black population is affected by chronic diabetes, and most of them are subjected to severe cardiovascular, renal, and neurological complications that shorten survival and diminish quality of life. One of the important pathogenetic mechanisms under intensive investigation is advanced tissue glycosylation. Tissue and cell surface proteins modified nonenzymatically by glucose are shown to be highly active in protein cross-linking and have been implicated in tissue damage. Such protein-glucose interactions, called advanced glycosylation end products (AGEs), are processed by macrophages through a high-affinity receptor. Coupling of AGE proteins to their AGE receptors results in their degradation and removal and, simultaneously, in synthesis and secretion of pluripotential cytokines such as tumor necrosis factor and interleukin 1. This suggests that AGE may act normally as a signal for growth-promoting factor secretion in a coordinated replacement process during tissue remodeling. In chronic diabetes, however, where accelerated accumulation of tissue AGE occurs, a disturbance of this balance may lead to several pathological, lytic, and/or proliferative responses like those in the vasculopathy of diabetes. Progress has been made with the discovery of aminoguanidine HCl, an AGE inhibitor, which has prevented significant pathology in short-term diabetic animal studies.
Diabetes Care 1990 Nov
PMID:Chronic diabetic complications and tissue glycosylation. Relevant concern for diabetes-prone black population. 226 39

To determine the effects of acute metabolic acidosis and alkalosis on leucine metabolism in vivo, mongrel dogs were infused with [1-14C]leucine for 8 h, along with NaCl, HCI, or NaHCO3 over the last 4 h. Arterial pH did not change from the basal value during NaCl infusion but decreased (P less than .01) and increased (P less than .01) during HCl and NaHCO3 infusions, respectively. Total leucine carbon entry did not change from the basal value during saline infusion but increased (P less than .01) with acidosis and decreased (P less than .05) with alkalosis. Compared with saline controls, acidosis increased (P less than .01) leucine oxidation. During alkalosis decreased (P less than .01) leucine oxidation. During acidosis, total plasma essential and nonessential amino acid concentrations increased (P less than .05), whereas during alkalosis, total plasma essential and nonessential amino acid concentrations decreased (P less than .05). These studies suggest that acute alterations in arterial pH may affect the regulation of protein metabolism in vivo and must be considered in the interpretation of results from experiments in which alterations of acid-base homeostasis may have occurred.
Diabetes 1989 Jul
PMID:Effects of acute metabolic acidosis and alkalosis on leucine metabolism in conscious dogs. 254 71

The specific activities of membrane-bound maltase (alpha-D-glucoside glucohydrolase, EC 3.2.1.20) in isolated brush border membranes (BBMs) of alloxan-induced diabetic, glucose-infused and maltose-infused rabbits were 30%, 140% and 160%, respectively, of those of control rabbits. Differences in the relative activities of trehalase (EC 3.2.1.28), another disaccharidase, in these groups were similar but less marked. However, the activities of two other marker enzymes of the brush border, alkaline-phosphatase and gamma-glutamyl transpeptidase, were similar in the 4 groups of rabbits. The decreases in the activities of the two disaccharidases were due to changes in the Vmax values of the enzymes without change in their Km values for maltose and trehalose. The maltase activities in the 4 groups showed similar dependences on Tris-HCl, KCl and NaCl. The electrophoretic profiles of the BBMs of the 4 groups on SDS-polyacrylamide gel showed slight differences. From these results, we conclude that diabetes, glucose infusion and maltose infusion probably change the concentrations of active enzymes in the BBM of the kidney in rabbits.
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PMID:Comparisons of maltase activities in kidney brush border membranes from normal, diabetic, glucose-infused and maltose-infused rabbits. 266 45

The effect of thyroxine (T4) on T4 conversion to triiodothyronine (T3) and reverse T3 (rT3) was studied in BB/W rats. A colony of 38 BB/W rats was obtained and half were treated with thyroxine (T4), 1 mg per liter of drinking water. At 106 days of age the following groups were identified: nondiabetic, no T4 treatment, 8 rats; nondiabetic, T4 treated, 8 rats; diabetic, no T4 treatment, 10 rats; diabetic, T4 treated, 7 rats. All animals with diabetes were treated with insulin. T4 conversion to T3 and rT3 was assessed in liver homogenates in 0.1 M Tris-HCl buffer, pH 7.4, with or without 5 mM dithiothreitol (DDT). Serum T4 and rT3 were significantly elevated in both T4-treated groups (P less than 0.001), while serum T3 was not affected in either. Basal T4 deiodination to T3 by the liver homogenate did not change on treatment with T4; the addition of DTT increased T3 production in the homogenate from T4 treated nondiabetic animals (P less than 0.05). In both nondiabetic and insulin-treated diabetic rats there was no effect of T4 on the rate of rT3 production. Since, in the rat, 30-40% of circulating T3 is a direct contribution of thyroid gland secretion, and that would be absent in our T4-suppressed animals, the normal serum T3 may reflect increased absolute peripheral T3 production from the greater concentration of circulating T4.
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PMID:A study of hepatic metabolism of thyroxine in BB/W rats treated with L-thyroxine. 272 30

Forty milligrams papaverine HCl was intracavernously injected to 28 patients with erectile dysfunction for diagnosis and treatment in 14 cases in which it was injected a few times. We designed a brief manual method for measurement of penile hardness by artificial erection. Twenty of the patients corresponding to 71.4%, reacted, but only 16 (57.1%) had efficient erection for possibility of coitus. It was useful for the diagnosis of vascular dysfunction with dorsal penile arterial pulse sound examination in impotence. It was useful for the cases of small vascular impediment with preservation of nerve supply after the operation of intrapelvic malignancies, and self injection might be possible, but on the other hand, it had no effect for the patients of advanced age with vascular impediment and diabetes mellitus neuropathy, and with arteriosclerosis.
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PMID:[Investigation of intracavernous injection of papaverine for erectile impotence]. 272 23


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