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)

Carnitine (beta-hydroxy-gamma-N-trimethylaminobutyric acid) is required for transport of long-chain fatty acids into the inner mitochondrial compartment for beta-oxidation. Widely distributed in foods from animal, but not plant, sources, carnitine is also synthesized endogenously from two essential amino acids, lysine and methionine. Human skeletal and cardiac muscles contain relatively high carnitine concentrations which they receive from the plasma, since they are incapable of carnitine biosynthesis themselves. Since the discovery of a primary genetic carnitine deficiency syndrome in 1973, carnitine has become the subject of extensive research. It is now recognized that carnitine deficiency may also occur secondary to genetic disorders of intermediary metabolism as well as to a variety of clinical disorders, including renal disease treated by hemodialysis, the renal Fanconi syndrome, cirrhosis, untreated diabetes mellitus, malnutrition, Reye's syndrome, and certain disorders of the endocrine, neuromuscular, and reproductive systems. Administration of the anticonvulsant valproic acid and total parenteral nutrition may also induce hypocarnitinemia. In many instances, the physiological implications of secondary carnitine deficiency have not been resolved. However, evidence for a specific carnitine requirement for the newborn, especially if preterm, is accumulating. Moreover, carnitine administration may have a favorable effect on some forms of hyperlipoproteinemia. Carnitine, now recognized as a conditionally essential nutrient, is a significant factor in preventive medicine.
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PMID:Carnitine: an overview of its role in preventive medicine. 353 87

The effect of heparin, a polyanionic glycosaminoglycan known to alter the function of many proteins, on insulin binding and bioactivity was studied. Cultured human lymphocytes (IM-9) were incubated with varying concentrations of heparin, then extensively washed, and 125I-labeled insulin binding was measured. Heparin at concentrations used clinically for anticoagulation (1-50 U/ml) inhibited binding in a dose-dependent manner; 50% inhibition of binding occurred with 5-10 U/ml. Scatchard analysis indicated that the decrease in binding was due to a decrease in both the affinity and the apparent number of available insulin receptors. The effect occurred within 10 min at 22 degrees C and persisted even after the cells were extensively washed. Inhibition of insulin binding also occurred when cells were preincubated with heparinized plasma or heparinized serum but not when cells were incubated with normal serum or plasma from blood anticoagulated with EDTA. By contrast, other polyanions and polycations, e.g., poly-L-glutamic acid, poly-L-lysine, succinylated poly-L-lysine, and histone, did not inhibit binding. Heparin also inhibited insulin binding in Epstein-Barr (EB) virus-transformed lymphocytes but had no effect on insulin binding to isolated adipocytes, human erythrocytes, or intact hepatoma cells. When isolated adipocytes were incubated with heparin, there was a dose-dependent inhibition of insulin-stimulated glucose oxidation and, to a lesser extent, of basal glucose oxidation. Although heparin has no effect on insulin binding to intact hepatoma cells, heparin inhibited both insulin binding and insulin-stimulated autophosphorylation in receptors solubilized from these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1987 Feb
PMID:Effects of heparin on insulin binding and biological activity. 354 43

The biochemical and biomechanical properties of aortas from diabetic rats were investigated after a period of three months. Diabetes caused increased non-enzymatic glycosylation of lysine and hydroxylysine residues of collagen, whereas no changes were found in the reducible collagen cross-links. Although diabetes caused a reduction in the thickness of the aortic wall and a decrease in the dry weight and amount of collagen and elastin per mm2, no changes were found in the mechanical strength and stiffness of the wall. When the mechanical parameters were corrected for the decrease in dry weight, the tensile strength of the aortic wall was found to be increased compared with the control group. This increase in the stability of aortic collagen can be explained by formation of reactive carbonyl compounds from the glycosyllysines, resulting in stabile cross-links between the collagen molecules.
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PMID:Changes in collagen and elastin of the rat aorta induced by experimental diabetes and food restriction. 361 83

Lens crystallins undergo non-enzymatic glycosylation with aging and diabetes mellitus. It is not known, however, whether all crystallins are subject to the same extent of glycosylation. Human diabetic lenses (approximately 80 years of age) were dissected into cortex and nucleus, then fractionated into various crystallins with gel chromatography (Sephacryl S-200, Sephadex G-75 or Bio Gel A-15m). The glycosylated crystallins were then separated from the nonglycosylated crystallins by affinity chromatography on Glyco Gel B boronic acid. The percentage of glycosylated crystallin was about 20-30%, and did not differ much among most crystallins, although gamma-crystallin has significantly less (p less than 0.01) glycosylated protein. The extent of glycosylation in the glycosylated crystallins, however, was found to be greater in the high molecular weight crystallins. The extent of glycosylation in alpha-crystallins is approximately two to four times that observed in beta- or gamma-crystallin. The extent of glycosylation appears to depend not only on the lysine content, which does not vary much among the crystallins, but also on the accessibility of the surface areas where lysine residues are located. This accessibility depends on the protein conformation and appears to correlate with protein unfolding.
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PMID:Non-enzymatic glycosylation in human diabetic lens crystallins. 371 14

To determine if renal functional alterations in diabetes mellitus could be related to disturbances of vasoactive systems, renal plasma flow (RPF), glomerular filtration rate (GFR), PRA (basal and stimulated), plasma catecholamine levels, and urinary excretion of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, and kallikrein were determined in 21 patients with insulin-dependent diabetes mellitus (IDDM) of short duration and 15 normal subjects. In 7 additional patients with IDDM and in 4 normal subjects, the effect of lysine acetylsalicylate (LAS; 450 mg, iv) on GFR and RPF was studied. Patients with IDDM had higher RPF and GFR than normal subjects. Plasma norepinephrine and basal and stimulated PRA were significantly lower in IDDM than in the control group [161 +/- 82 (+/- SD) vs. 243 +/- 114 pg/ml, 0.19 +/- 0.20 vs. 1.15 +/- 0.33 ng/ml X h, and 0.93 +/- 0.82 vs. 2.8 +/- 1.73 ng/ml X h, respectively). No significant differences were found in the urinary excretion of PGE2, 6-keto-PGF1 alpha, and kallikrein in the two groups. LAS administration significantly reduced RPF (from 641 +/- 72 to 535 +/- 38 ml/min X 1.73 m2) and GFR (from 168 +/- 25 to 150 +/- 18 ml/min X 1.73 m2) in patients with IDDM, but not in normal subjects. In IDDM patients, there was a close direct correlation between the percent decrease in RPF and GFR induced by LAS and the baseline values of these parameters. The results suggest that in IDDM, there may be an imbalance between the degree of activation of the renin-angiotensin and sympathetic nervous systems and the renal production of PGs. The observation that LAS administration reduced RPF and GFR in these patients suggests that renal PGs are involved in the renal hyperperfusion of IDDM.
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PMID:Renal hemodynamic abnormalities in patients with short term insulin-dependent diabetes mellitus: role of renal prostaglandins. 385 81

The effects of various degrees of reductive and nonreductive glucosylation of low density lipoprotein on its catabolism by human fibroblasts have been examined. Moderate glucosylation of LDL does not alter its interaction with the high affinity receptor at concentrations of 5-2000 micrograms LDL-cholesterol/ml. Only heavy glucosylation of LDL (more than 12 lysine residues glucosylated per apo B), i.e. conditions not expected to occur in diabetes, slows receptor-mediated internalisation and degradation. In contrast, impairment of LDL-catabolism has been found at even low degrees of reductive glucosylation. The possible reasons for the different properties of reductively and nonreductively glucosylated LDL are discussed.
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PMID:Different effects of reductive and nonreductive glucosylation on LDL-catabolism. 386 87

The relationships between changes in the plasma levels of immunoreactive insulin (IRI) and glucagon (IRG) in response to the postprandial increments of circulating amino acids were studied under normal physiological conditions in healthy dogs. In the presence of a unique postprandial physiological euglycemic "glucose clamp" which occurs in these dogs, plasma IRG rose to an earlier peak than IRI and both remained elevated for 16-19 hr. Amino acid (AA) profiles also showed postprandial incremental responses for up to 16 hr. Multiple correlation analyses indicated that only branched chain AAs were significantly correlated with IRI profiles and were devoid of a relationship to IRG. Similarly, only ornithine, lysine and glycine were significantly correlated with IRG profiles and devoid of a relationship to IRI. The significance of individual IRG stimulating effects of alanine and arginine were masked by other amino acid interactions, as significant intercorrelation was found among all 13 amino acids. Two equations were derived from the multiple regression analysis accounting for the postprandial time course of changes in IRI and IRG levels with only 5 amino acid concentrations: (1) (delta IRI) = 0.37 (delta Leu) -0.45(delta His), and (2) (delta IRG) = 0.55(delta Orn) + 0.37(delta Gly) -0.69 (delta Ser). These observations confirm the physiologic role in islet hormone secretion of the postprandial increments in circulating amino acids in the absence of glycemic change.
Diabetes Res 1985 Jan
PMID:Changes in blood amino acids account for the insulin and glucagon responses to mixed meals in dogs. 388 96

Rabbit forelimb tendons incubated for 15 or 21 days at 35 degrees C in the presence of 8 or 24 mg of glucose/ml were shown to change their chemical, biochemical and mechanical characteristics. The tendons treated with glucose contained up to three times as much hexosyl-lysine and hexosylhydroxylysine as did control tendons as judged by assay of NaB3H4-reduced samples. Measurement of the force generated on thermal contraction showed significant increases in glycosylated tendons compared with controls, indicating the formation of new covalent stabilizing bonds. This conclusion was supported by the decreased solubility of intact tendons and re-formed fibres glycosylated in vitro, and by the evidence from peptide maps of CNBr-digested glucose-incubated tendons. The latter, when compared with peptide maps of control tendons, revealed the presence of additional high-Mr peptide material. These peptides appear to be cross-linked by a new type of covalent bond stable to mild thermal and chemical treatment. This system in vitro provides a readily controlled model for the study of the chemistry of changes brought about in collagen by non-enzymic glycosylation in diabetes.
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PMID:Evidence for glucose-mediated covalent cross-linking of collagen after glycosylation in vitro. 391 11

Nonenzymatic posttranslational glucosylation of the free amine of lysine residues can occur in hyperglycemic diabetic subjects. Using monoclonal antibodies that specifically bind the reduced conjugate of glucose covalently bound to the epsilon amine of lysine, glucitollysine, plasma lipoprotein glucosylation was demonstrated by radioimmunoassays in all subjects tested. Lipoproteins isolated from the plasma of diabetic subjects in poor metabolic control contained up to 33-fold increases in glucitollysine residues/mg of isolated lipoprotein protein, and on an absolute basis contained between 36 and 383 nmol of glucitollysine in their total lipoprotein fraction compared with normals, who had a mean of 2.9 +/- 0.06 nmol. The majority of the glucosylated protein in the d less than 1.125 g/ml fraction was present in the triglyceride-rich lipoproteins of hyperglycemic subjects, whereas the majority of the glucosylated protein in the d less than 1.125 g/ml fraction of euglycemic subjects was present in the high-density lipoproteins (HDL). A number of immunochemical approaches were used to demonstrate that, in diabetic plasma, apo AI, apo AII, apo B, apo CI, apo E, and albumin were glucosylated. Detailed studies of the apoproteins of a d less than or equal to 1.019 g/ml lipoprotein fraction and of an HDL fraction isolated from a hyperglycemic diabetic subject indicated that glucitollysine-specific antibodies can be used to preparatively isolate proteins containing glucosylated amino acid residues so that the extent of glucosylation in specific proteins can be measured. The results indicate that some of the lysine residues of the apoproteins can be modified in hyperglycemic diabetic subjects by the covalent attachment of glucose. The possible significance of these observations is discussed.
Diabetes 1985 May
PMID:Plasma apolipoproteins AI, AII, B, CI, and E are glucosylated in hyperglycemic diabetic subjects. 392 19

To assess whether the beneficial effects of salicylates compounds and sulfonylureas on insulin secretion in patients with noninsulin-dependent diabetes mellitus could be ascribed to inhibition of prostaglandin E (PGE) synthesis, insulin responses to iv glucose pulses were determined in diabetic patients during infusion of lysine acetylsalicylate (LAS) or tolbutamide, with or without a concurrent infusion of PGE2. In these diabetic patients, the augmenting effects of LAS on glucose-induced insulin secretion were abolished by PGE2 infusion. Partial restoration by tolbutamide infusion of the first and second phases of glucose-induced insulin secretion was not affected by the administration of PGE2. The stimulatory effects of LAS and tolbutamide on insulin secretion were additive, suggesting separate mechanisms of action. Since salicylates and sulfonylureas lower plasma glucose concentrations, we also evaluated whether prevention of the fall in the prestimulus glucose level could result in a further amplification of insulin release. Resetting the prestimulus glucose level to control values by infusing glucose caused a further increase in the second, but not the first, phase of glucose-induced insulin secretion, indicating that the prestimulus glucose level had a role in regulating subsequent insulin release. These results indicate that salicylates, but not sulfonylureas, exert their acute insulinotropic effect in noninsulin-dependent diabetic patients by inhibiting endogenous PGE synthesis and support the idea that endogenous PGE may play a role in the impaired insulin response to glucose in this form of human diabetes.
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PMID:Effects of salicylate, tolbutamide, and prostaglandin E2 on insulin responses to glucose in noninsulin-dependent diabetes mellitus. 392 28


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