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

gamma-Aminobutyric acid (GABA) is the most widely distributed known inhibitory neurotransmitter in the vertebrate brain. GABA also serves regulatory and trophic roles in several other organs, including the pancreas. The brain contains two forms of the GABA synthetic enzyme glutamate decarboxylase (GAD), which differ in molecular size, amino acid sequence, antigenicity, cellular and subcellular location, and interaction with the GAD cofactor pyridoxal phosphate. These forms, GAD65 and GAD67, derive from two genes. The distinctive properties of the two GADs provide a substrate for understanding not only the multiple roles of GABA in the nervous system, but also the autoimmune response to GAD in insulin-dependent diabetes mellitus.
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PMID:Two genes encode distinct glutamate decarboxylases. 206 16

The effects of vitamin B6 on erythrocyte metabolism, erythrocyte hemoglobin O2 affinity (P50), and nonenzymatic glycosylation were studied in 15 Caucasian men with type II (non-insulin-dependent) diabetes mellitus. A control group of 13 healthy Caucasian men was also evaluated. Before treatment, diabetic subjects had low mean cell hemoglobin concentration values and increases in both erythrocyte 2,3-diphosphoglycerate (2,3-DPG) levels and erythrocyte hexokinase activities. Although all three of these changes are associated with a decrease in hemoglobin O2 (Hb-O2) affinity, P50 values were normal in diabetic subjects. Moreover, P50 values normalized to pH 7.4 (P50(7.4] were inversely related to the level of glycosylated hemoglobin (HbA1c). Both erythrocyte 2,3-DPG and erythrocyte ATP were also inversely related to HbA1c. Vitamin B6 nutriture, as determined by erythrocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, was normal in all diabetic subjects before vitamin B6 therapy. Nonetheless, HbA1c levels decreased after 6 wk of treatment with 150 mg/day pyridoxine and increased again during placebo administration. These changes were not explained by changes in fasting blood glucose. Pyridoxine therapy also decreased P50(7.4) values and increased erythrocyte AST and ALT activities but had no effect on 2,3-DPG, ATP, or the activities of hexokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. These observations suggest that 1) nonenzymatic glycosylation may play a role in regulating both erythrocyte metabolism and Hb-O2 affinity in diabetic subjects, and 2) vitamin B6 therapy may modify nonenzymatic glycosylation of hemoglobin in this population.
Diabetes 1989 Jul
PMID:Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus. 273 64

The streptozotocin diabetic rat was selected as a model to study how insulin deficiency alters vitamin B6 utilization by focusing on pyridoxal phosphate levels and aspartate aminotransferase activities in liver tissues. Diabetes of 15 weeks' duration lowered plasma pyridoxal phosphate levels by 84%. Normal plasma pyridoxal phosphate was 480 pmole/ml. Fractionation of liver into mitochondrial and extramitochondrial compartments demonstrated that diabetes caused a 43% diminution in mitochondrial pyridoxal phosphate per gram of liver. There was no cytoplasmic change in these diabetic rats. Mitochondrial aspartate aminotransferase activity was decreased 53% per gram of diabetic liver and cytoplasmic aspartate aminotransferase activity was elevated 3.4-fold. Damage to diabetic mitochondria during preparation procedures could not account for the rise in cytoplasmic aspartate aminotransferase activity. Electrophoresis showed that in the diabetic cytoplasm both cathodal and anodal forms of the enzyme were elevated. Speculations concerning mitochondrial loss and cytoplasmic gain of enzyme activity as well as those on the reduction of plasma pyridoxal phosphate in the diabetic rat are presented.
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PMID:Experimental diabetes causes mitochondrial loss and cytoplasmic enrichment of pyridoxal phosphate and aspartate aminotransferase activity. 374 6

The composition and nutritional adequacy of subject-selected high carbohydrate, low fat diets were investigated in six women with insulin-dependent diabetes mellitus. Subjects were randomly assigned to begin either the experimental diet with 65% carbohydrate, 20% fat, and 15% protein for 6 wk, or a control diet with 45% carbohydrate, 40% fat, and 15% protein for 4 wk. All subjects completed both dietary periods in a cross-over experimental design. Subjects were allowed free selection in their choice of carbohydrate-rich foods. The resulting selections produced diets with 51% simple and 49% complex carbohydrates and 50 g of dietary fiber during the experimental diet. Similar proportions were also selected during the control diet. Blood chemistries revealed no significant changes in thiamin, riboflavin, vitamin B6, pyridoxal 5'-phosphate, ascorbate, vitamin E, calcium, selenium, or zinc concentrations between the two dietary periods. With the exception of vitamin B6, all vitamin and mineral values were within normal respective ranges. Vitamin B6 status, as assessed by pyridoxal 5'-phosphate, were below or just above the levels of marginal deficiency (2.2 nmol/100 ml) in four of the six individuals, but the lower level observed occurred independent of the dietary treatments. The present study demonstrates that subject-selected high carbohydrate, low fat diets were much lower in complex carbohydrates and fiber than diets previously tested. In addition, the concentration of several nutrients did not appear to be adversely affected by these diets.
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PMID:The composition and nutritional adequacy of subject-selected high carbohydrate, low fat diets in insulin-dependent diabetes mellitus. 634 10

To determine the role of pyridoxine in the treatment of diabetic peripheral neuropathy, 18 symptomatic diabetic patients were treated with vitamin B6 or placebo in a double-blind controlled study. Only one patient had a low plasma pyridoxal phosphate level at the start of the study. After 4 mo of treatment with pyridoxine hydrochloride (50 mg three times daily) 6 of 9 pyridoxine-treated and 4 of 9 placebo-treated patients noted significant relief from their neuropathic symptoms. There was no difference between the two groups with regard to fasting plasma glucose, motor nerve conduction velocity, or ophthalmologic examination at the beginning or at the conclusion of the study. Our results suggest that vitamin B6 deficiency is not a factor in the etiology of diabetic peripheral neuropathy. Furthermore, treating diabetic peripheral neuropathy with high dose vitamin B6 or placebo results in a similar frequency of symptomatic improvement.
Diabetes Care
PMID:The influence of pyridoxine in diabetic peripheral neuropathy. 675 36

Because the supplementation of pyridoxine (vitamin B6) improves the glucose tolerance in gestational diabetes and adult onset diabetes, pyridoxine deficiency has been considered to be one of the factors that cause diabetes mellitus. We produced pyridoxine deficient rats by giving pyridoxine-free food with deoxypyridoxine which competitively the activity of pyridoxal phosphate. In these pyridoxine deficient rats plasma insulin during the glucose tolerance test was significantly low as compared with controls. In vitro experiments of pancreas perfusion showed that secretion of insulin and glucagon was impaired in the pyridoxine deficiency. Since the restriction of diet-calorie caused a decrease in arginine-induced secretion of insulin and glucagon from the isolated pancreas, the impairment of the endocrine pancreas may depend on malnutrition. Pyridoxine deficiency is surely one of the factors that impair the endocrine pancreas by multifactorial derangement of metabolism besides the tryptophan-nicotinic acid pathway.
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PMID:The endocrine pancreas in pyridoxine deficient rats. 703 87

A study was undertaken to test the effect of pyridoxine supplementation on glucose tolerance in diabetes mellitus. Thirteen adult maturity-onset diabetics were studied. Seven were vitamin B6 deficient, as assessed by the stimulation of erythrocyte glutamic oxaloacetic transaminase in vitro by pyridoxal phosphate. All patients received pyridoxine hydrochloride (40 mg twice daily) for 3 weeks. Pyridoxine supplmentation did not bring about any significant alterations in either the oral glucose tolerance or the insulin response to glucose.
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PMID:Failure of pyridoxine to improve glucose tolerance in diabetics. 718 14

Different autoantigens are thought to be involved in the pathogenesis of insulin-dependent diabetes mellitus, and they may account for the variation in the clinical presentation of the disease. Sera from patients with autoimmune polyendocrine syndrome type I contain autoantibodies against the beta-cell proteins glutamate decarboxylase and an unrelated 51-kDa antigen. By screening of an expression library derived from rat insulinoma cells, we have identified the 51-kDa protein as aromatic-L-amino-acid decarboxylase (EC 4.1.1.28). In addition to the previously published full-length cDNA, forms coding for a truncated and an alternatively spliced version were identified. Aromatic L-amino acid decarboxylase catalyzes the decarboxylation of L-5-hydroxytryptophan to serotonin and that of L-3,4-dihydroxyphenylalanine to dopamine. Interestingly, pyridoxal phosphate is the cofactor of both aromatic L-amino acid decarboxylase and glutamate decarboxylase. The biological significance of the neurotransmitters produced by the two enzymes in the beta cells remains largely unknown.
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PMID:Aromatic-L-amino-acid decarboxylase, a pyridoxal phosphate-dependent enzyme, is a beta-cell autoantigen. 756 87

Homogenates of pancreatic islets catalyzed breakdown of L-glutamate to GABA with a rate of 0.24 +/- 0.04 nmol.min-1 x mg-1 protein at 37 degrees C. The formation of GABA was stimulated by addition of pyridoxal phosphate in the range 0.05-1 microM (0.97 +/- 0.02 nmol.min-1 x mg protein-1 at a saturating cofactor concentration), which indicates that the process was catalyzed by glutamic acid decarboxylase. The half-maximal effect was obtained with 0.1 microM PLP. Kinetic analyses of the results showed that the Vmax and Km for the reaction were 1.12 nmol.min-1 x mg protein-1 and 0.66 mM, respectively. The pH optimum was 7.0. Subcellular fractionation revealed that 51% of GAD activity was present in the cytosol, 17% in microsomes, 9% in secretory granules, 5% in mitochondria, and 11% in cell debris. Comparison of the kinetic properties of the cytosolic and microsomal forms of the enzyme showed that their Km for glutamate was the same, but that the cytosolic GAD had a lower Km for PLP. GABA synthesis in the nominal absence of PLP was enhanced by malate (twofold increase at 5 mM) and citrate (threefold increase at 5 mM), but was unaffected by ATP and chloride. However, if the islet homogenate was prepared and incubated in the presence of PLP, neither malate nor citrate influenced enzyme activity. Aspartate and AOA were powerful inhibitors of glutamate breakdown. Freshly isolated islets contained approximately 4 mM GABA, whereas the concentration was < 0.1 mM in whole pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Oct
PMID:GABA production in rat islets of Langerhans. 837 91

By mathematically analysing the curves of urinary excretion of vitamins, their plasma and erythrocytic concentrations or of TDP-effect, by constructing and mathematically interpreting the variation curves of distribution of a given plasma concentration of riboflavin and pyridoxal phosphate for 10-14-old-year children suffering from insulin-dependent diabetes mellitus after supplementation of vitamin, as a criterion of normal requirement for vitamin B2, the authors are prone to recommend the concentration of riboflavin over 10 micrograms/ml in plasma and over 96 micrograms/ml in erythrocytes, the hourly excretion of more than 27 micrograms. It has been ascertained that the criteria for the optimal body's requirements for vitamins in diabetes mellitus children do not differ from those in healthy age-matched children. Thus, the value of TDP-effect is less than 1.25, the concentration of pyridoxal phosphate is over 8.4 micrograms/ml plasma, the excretion values of thiamine and 4-pyridoxic acid are 13.5 and 64.0 micrograms/h, respectively.
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PMID:[Criteria of supply of vitamins B1, B2, and B6 in children with insulin-dependent diabetes mellitus]. 861 8


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