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

We measured how much glycated protein there was in rat eye lenses with different degrees of cataract, using an antibody against glucitol-lysine. Streptozotocin-diabetic (STZ) rats were in some cases treated with insulin (STZ + INS); control rats were normal. We graded the cataracts from 0 (transparent) to 3 (entirely opaque). STZ rats had significantly more grade 3 cataracts, and STZ + INS rats more grade 1 cataracts, than other groups. Grade 3 lenses had significantly more glycated protein than those of grade 0 (10.8 +/- 2.7 vs. 1.0 +/- 0.4 nmol/mg protein), grades 1 and 2 being intermediate. Glycosylated hemoglobin levels correlated similarly with severity of cataract. These data are consistent with the greater incidence of cataract among diabetics than among non-diabetics, and suggest that lens protein glycation contributes to the development of cataract.
Diabetes Res Clin Pract 1989 Nov 06
PMID:Lens protein glycation and the subsequent degree of opacity in streptozotocin-diabetic rats. 269 28

Insulin receptor complementary DNA has been cloned from an insulin-resistant patient with leprechaunism whose receptors exhibited multiple abnormalities in insulin binding. The patient is a compound heterozygote, having inherited two different mutant alleles of the insulin receptor gene. One allele contains a missense mutation encoding the substitution of glutamic acid for lysine at position 460 in the alpha subunit of the receptor. The second allele has a nonsense mutation causing premature chain termination after amino acid 671 in the alpha subunit, thereby deleting both the transmembrane and tyrosine kinase domains of the receptor. Interestingly, the father is heterozygous for this nonsense mutation and exhibits a moderate degree of insulin resistance. This raises the possibility that mutations in the insulin receptor gene may account for the insulin resistance in some patients with non-insulin-dependent diabetes mellitus.
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PMID:Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance. 283 24

Amino sugars such as galactosamine are hepatotoxic. It has been verified that toxic hepatitis induced by galactosamine is similar to that of CCl4 poisoning, and that both were inhibited by O2* scavengers. Fructosamine results from the union of glucose with the epsilon-amine of lysine. A test for fructosamine quantification is based on nitroblue tetrazolium (NBT) reduction, in which O2- is involved, the reduction being inhibited in the presence of superoxide dismutase (SOD). Given these facts, we attempted to elucidate if galactosamine and glucosamine reduce NBT and if that reduction is inhibited by SOD. This was confirmed. Subsequently, we incubated aminoacids (glycine, lysine, alanine) with glucose and galactose for 7 days and studied the action of the incubation products on NBT, using amino acids and sugars as controls. We found that NBT reduction increases proportionally to the length of incubation time of glucose/galactose with lysine, but not with other amino acids. Reduction of NBT by the Amadori compounds formed is inhibited by SOD. We suggest that oxygen radical generation by Amadori compounds must be taken into consideration as one cause of damage in diabetes of long duration.
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PMID:Oxygen radical generation by Maillard compounds. 283 94

Several D-sugars were incubated with L-lysine or with L-arginine for 10 days. The resulting compounds are able to reduce nitrobluetetrazolium (NBT). This is prevented by superoxide dismutase (SOD), indicating that the superoxide radical is generated by the resulting Amadori compounds. The formation of superoxide radical in vivo, as a result of nonenzymatic glycosylation of proteins, may be considered to be a contributory factor to the appearance of chronic complications of diabetes.
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PMID:Superoxide radical generation by Amadori compounds. 285 11

This study provides explanation for conflicting evidence in the literature relating to changes in mitochondrial function and metabolic parameters during chemically induced diabetes. Diabetes of 3 days' duration (early ketosis) did not alter heart, kidney, or liver mitochondrial respiratory rates with glutamate or succinate even though serum glucose and triglycerides were elevated. Diabetes of 5 weeks' duration did not alter kidney or liver mitochondrial function in the fed adult rat although weight gain was depressed. The amount of kidney mitochondrial protein isolated per gram of tissue was increased by 30% in the diabetic. This increase was reversed by insulin treatment as were the other biochemical modalities measured. Superimposition of a 24-hr fast resulted in enhanced gluconeogenesis as measured by an animal weight loss of 17% within 24 hr (liver weight loss, 21%) and an elevation of serum urea nitrogen by 180% compared to fasted control. Respiratory rates of diabetic kidney mitochondria with glutamate were unaffected in the fasted animal whereas diabetic liver mitochondrial respiratory rates during succinate oxidation were reduced by 43%. Respiratory control was unchanged in the fasted diabetic rat. All the observed changes were reversed by insulin. Variation in the serum and liver metabolic indices (urea nitrogen, creatinine, glycerol, free fatty acids, free amino acids, triglycerides, and glucose) and liver mitochondrial responses to 7 weeks of chemically induced diabetes was affected by the rat strain, Sprague-Dawley versus Sherman, and rat weight, 72 g versus 222 g. Liver mitochondrial respirations in fed Sherman rats were not depressed by diabetes. Both rat strains had elevated liver free fatty acids and glutamate dehydrogenase activity in the diabetic state. Serum leucine, isoleucine, and valine were more elevated and serum lysine and arginine were more depressed in the diabetic Sprague-Dawley rat than in the Sherman rat. Conjectures on these results are presented in the text.
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PMID:Metabolic and mitochondrial disturbances in streptozotocin-treated Sprague-Dawley and Sherman rats. 293 62

Renal handling of 125I-insulin was studied using a modification of the Sperber technique. Results showed 125I-insulin to be extracted at the peritubular side of the nephron in a process that was competitively inhibited by increasing amounts of unlabelled insulin, but not ACTH, in the injection mixture. When unlabelled insulin instead was injected 30 sec after the labelled insulin it showed significantly less interference with peritubular extraction of 125I-insulin, indicating strong attachment to the cell membrane or possible internalization of 125I-insulin into proximal tubular cells. Light microscope autoradiography 1 min after injection of 125I-insulin showed grains over proximal tubules only. On the ligated side localization was preferably peritubular while on the control side it was luminal. Electron microscope autoradiography showed sparsely distributed grains, however, frequently located over basal parts of proximal tubular cells. Pretreatment with lysine hydrochloride lowered renal extraction of 125I-insulin and increased urinary recovery of iodine label bilaterally. 125I-glucagon and 125I-C-peptide were not extracted from the peritubular circulation. In conclusion, the model has provided evidence of a rapid and significant peritubular extraction of 125I-insulin by proximal tubular cells in a process probably involving specific insulin receptors. Following receptor binding probably only minor amounts of 125I-insulin enters the proximal tubular cells, while the greater part is degraded at the cell surface or released into the circulation.
Diabetes Res 1985 May
PMID:Renal handling of 125I-labelled insulin in the hen. 299 79

The catabolism of low-density lipoproteins (LDL), the major cholesterol-carrying lipoproteins in plasma, is mediated in part via a high-affinity uptake pathway in the liver. Non-enzymatic glucosylation of lysine residues of apolipoprotein B, the major protein of LDL, blocks receptor-mediated uptake of LDL by fibroblasts and endothelial cells. We investigated the effect of the degree of glucosylation on the binding, uptake and degradation of radioiodinated LDL by the human hepatoma cell line Hep G2. Human LDL was glucosylated with 250 mM glucose and 30 mM cyanoborohydride at 37 degrees C. Incubations ranging from 3 to 48 h in duration resulted in the formation of 6-27% of glucitol-lysine adducts as demonstrated by coincubation with [14C]glucose. The degree of glucose incorporation corresponded to the extent of inhibition of binding, uptake and degradation of LDL (10-90%). The data are consistent with the view that glucosylation of LDL markedly impairs their catabolism. This phenomenon may be related to the pathophysiology of the premature atherosclerosis observed in diabetes mellitus.
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PMID:Impaired hepatocyte binding, uptake and degradation of glucosylated low-density lipoproteins. 301 18

Amyloid deposits occurring in the islets of Langerhans in patients with noninsulin-dependent diabetes mellitus and some insulinomas contain a 37-amino acid peptide that is structurally related to calcitonin gene-related peptide. We have identified three cDNA clones encoding islet amyloid polypeptide (IAPP) or diabetes-associated peptide (DAP) by oligonucleotide screening of a lambda gt10 human insulinoma cDNA library. Two of the three cDNAs contained a domain encoding IAPP/DAP but had an intron-like sequence in their 5' region. The other cDNA contained an open reading frame encoding an 89-amino acid precursor having a typical signal peptide followed by a small prohormone-like sequence containing within it the IAPP/DAP peptide bracketed at its NH2 and COOH termini by Lys-Arg and Gly-Lys-Arg, respectively. These data indicate that this amyloid peptide is generated by proteolytic processing similar to that for proinsulin and other islet prohormones and also that the peptide may be carboxyamidated. The isolation of cDNA clones having 5'-unprocessed intron-like sequences suggests that inefficient or alternative splicing of this mRNA occurred in the insulinoma.
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PMID:An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing. 305 5

A competitive ELISA for quantitative determination of glucitollysine, the reduced hexose alcohol form of glucose conjugated to the epsilon amino group of lysine was developed. We applied it to measure non-enzymatically glycated serum proteins. The antiserum obtained by immunizing guinea pigs with reductively glycated human albumin was capable of identifying and quantitating glucitollysine residues of serum proteins in normal and diabetic subjects after reduction of the proteins with sodium borohydride. The ELISA assay developed here had satisfactory reproducibility as judged by the intra-assay precision of 2.3-7.6% and the interassay precision of 6.7-9.8%. Results from this assay procedure correlated well with those from the radioimmunoassay and the boronate affinity chromatography procedure. The data suggested that diabetic serum proteins contained at least three times as much immunochemically detectable glucitollysine residues as normal serum proteins after reduction of the proteins with sodium borohydride. This method allows to quantitate glucitollysine residues on any of the proteins that have been implicated in the pathological sequelae of diabetes.
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PMID:Quantitative enzyme-linked immunosorbent assay (ELISA) for non-enzymatically glycated serum protein. 310 4

Glycation of the aorta in rats with streptozotocin-induced diabetes was estimated by determining the early-stage product and the advanced product of the Maillard reaction. The early-stage product of the Maillard reaction was determined using furosine, which is derived from glycated lysine residues by acid hydrolysis. The advanced product was determined by fluorescence high-performance liquid chromatography. The levels of both early-stage and advanced products in diabetic rats were significantly higher than those in non-diabetic rats at the age of both 20 and 50 weeks. The levels of both early-stage and advanced products at 50 weeks in rats tended to be higher than those at 20 weeks. However, the level of glycated hemoglobin in both non-diabetic and diabetic rats showed no significant change between 20 and 50 weeks of age. These results suggest that tissue glycation may be involved in the development of diabetic complications and may be related to the aging mechanism.
Diabetes Res Clin Pract 1987 Nov
PMID:Accelerated glycation of the aorta in diabetic rats. 312 Dec 71


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