Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels of gamma aminobutyric acid decreased, while glutamic acid and aspartic acid levels increased in the forebrain, and decreased in the mid and hind brain regions of frog, Rana cyanophlictis during alloxan diabetes. Since glutamic acid and GABA are intimately involved in the central nervous system (CNS) functions, the alterations occurring in their levels during alloxan diabetes may be significant in bringing about a correlation between the diabetic state and the altered functional dynamics of the CNS.
 ...
PMID:Neurochemical correlates of alloxan diabetes: gamma amino butyric acid of amphibian brain. 89 69

The GABA-producing enzyme glutamate decarboxylase (GAD) is a prominent autoantigen in insulin-dependent diabetes mellitus (IDDM). Autoantibodies against GAD were found with a high prevalence in IDDM patients and in animal models for IDDM. The aim of this study was to detect autoantibodies against both isoforms of GAD in diabetic and non-diabetic but diabetes-prone BB/OK rats by Western blotting and to test their specificity to GAD by an immuno-trapping enzyme activity assay. Eighteen diabetic and 18 non-diabetic BB/OK rats (age 121 +/- 20 days) were investigated. In 10/18 (56%) of the diabetic and 13/18 (72%) of the non-diabetic BB/OK rats autoantibodies against at least one GAD-isoform were detected by Western blotting. In the immunotrapping enzyme activity assay, the mean value of the diabetic (1151 +/- 552 cpm, n = 11) and nondiabetic BB/OK rats (1978 +/- 1213 cpm, n = 10) was significantly (p < 0.01) increased compared to the LEW. 1A control rats (581 +/- 274 cpm, n = 12). 7/10 (70%) individual sera of the non-diabetic and 5/11 (45%) of the diabetic BB/OK rats were positive in this test. In conclusion, the prevalence of GAD autoantibodies in BB/OK rat is connected with the genetic susceptibility to IDDM but is not a predictor for the onset of the disease in BB/OK rats.
Diabetes Res 1992
PMID:Detection of antibodies against both isoforms of glutamate decarboxylase in BB/OK rats by western blotting and immuno trapping enzyme activity assay. 134 8

Conditions causing a reduction of oxygen availability (anoxia), such as stroke or diabetes, result in drastic changes in ion movements, levels of neurotransmitters and metabolites and subsequent neural death. Currently, there is no clinically available treatment for anoxia induced neural cell death resulting in drastic and permanent central nervous system dysfunction. However, there have been some exciting developments in experimentally induced anoxic conditions where several classes of drugs appear to significantly reduce neural cell death. This report aims to provide the foundations for understanding both the basic mechanisms involved in retinal ischaemic damage and experimental treatments used to prevent such damage. We discuss the normal release, actions and uptake of the fast retinal neurotransmitters, glutamate and GABA, in the vertebrate retina. Immunocytochemistry is used to demonstrate that both glutamate and GABA are found in the macaque retina. Following this is a discussion on how ischaemia may enhance neurotransmitter release or disrupt its uptake, thus causing an increase in extracellular concentration of these neurotransmitters and subsequent neuronal damage. The mechanisms involved in glutamate neurotoxicity are reviewed, because excess glutamate is the likely cause of retinal ischaemic damage. Finally, the mechanisms behind four possible modes of treatment of neurotransmitter toxicity and their advantages and disadvantages are discussed. Hopefully, further research in this area will lead to the development of a rational therapy for retinal, as well as cerebral ischaemia.
 ...
PMID:Interrelationship between retinal ischaemic damage and turnover and metabolism of putative amino acid neurotransmitters, glutamate and GABA. 136 7

The pancreatic islet beta-cell autoantigen of relative molecular mass 64,000 (64K), which is a major target of autoantibodies associated with the development of insulin-dependent diabetes mellitus (IDDM) has been identified as glutamic acid decarboxylase, the biosynthesizing enzyme of the inhibitory neurotransmitter GABA (gamma-aminobutyric acid). Pancreatic beta cells and a subpopulation of central nervous system neurons express high levels of this enzyme. Autoantibodies against glutamic acid decarboxylase with a higher titre and increased epitope recognition compared with those usually associated with IDDM are found in stiff-man syndrome, a rare neurological disorder characterized by a high coincidence with IDDM.
 ...
PMID:Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. 169 48

Stiff-Man syndrome (SMS) is a disorder of the CNS, characterized by rigidity of the body musculature, which has been hypothesized to result from an impairment of GABAergic neurotransmission. GABA is the main inhibitory neurotransmitter of the brain. It is also a putative signal molecule in the pancreas, where it is produced by beta cells (insulin-secreting cells)--the autoimmune target in insulin-dependent diabetes mellitus (IDDM). Autoantibodies to the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD) have been found in SMS and in IDDM. This review summarizes evidence suggesting that SMS may be an autoimmune disease and discusses the possible significance of the autoimmune response to GAD in SMS and IDDM.
 ...
PMID:Autoimmunity to glutamic acid decarboxylase (GAD) in Stiff-Man syndrome and insulin-dependent diabetes mellitus. 172 64

Insulin-dependent diabetes is an autoimmune disease that may be becoming more prevalent. It has a polygenic mode of inheritance with a major gene being present in the HLA DQ locus on chromosome 6. Inferential data suggest that environmental factors may be important to genetic penetrance albeit we still lack proof for involvement of often maligned viruses. Patients with IDD and their families are predisposed to organ-specific autoimmunities which should be routinely screened for. Autoantibodies to insulin, to a beta cell cytoplasmic lipid containing moiety and to a beta cell protein of 64KDa, which is believed to be the GABA forming enzyme GAD, can be used to predict IDD among relatives and probably the general population as well. Immunosuppressive therapy can modify the course of IDD after diagnosis and should be able to delay the clinical onset if given before diagnosis. Rigorous insulin therapy should also be given as needed to control hyperglycemia and avoid glucose toxicity to the islets. Such trials are now underway.
 ...
PMID:Immunology of diabetes mellitus. 832 19

gamma-Aminobutyric acid (GABA), a prominent inhibitory neurotransmitter, is present in high concentrations in beta-cells of islets of Langerhans. The GABA shunt enzymes, glutamate decarboxylase (GAD) and GABA transaminase (GABA-T), have also been localized in islet beta-cells. With the recent demonstration that the 64,000-M, antigen associated with insulin-dependent diabetes mellitus is GAD, there is increased interest in understanding the role of GABA in islet function. Only a small component of beta-cell GABA is contained in insulin secretory granules, making it unlikely that GABA, coreleased with insulin, is physiologically significant. Our immunohistochemical study of GABA in beta-cells of intact islets indicates that GABA is associated with a vesicular compartment distinctly different from insulin secretory granules. Whether this compartment represents a releasable pool of GABA has yet to be determined. GAD in beta-cells is associated with a vesicular compartment, similar to the GABA vesicles. In addition, GAD is found in a unique extensive tubular cisternal complex (GAD complex). It is likely that the GABA-GAD vesicles are derived from this GAD-containing complex. Physiological studies on the effect of extracellular GABA on islet hormonal secretion have had variable results. Effects of GABA on insulin, glucagon, and somatostatin secretion have been proposed. The most compelling evidence for GABA regulation of islet hormone secretion comes from studies on somatostatin secretion, where it has an inhibitory effect. We present new evidence demonstrating the presence of GABAergic nerve cell bodies at the periphery of islets with numerous GABA-containing processes extending into the islet mantle. This close association between GABAergic neurons and islet alpha- and delta-cells strongly suggests that GABA inhibition of somatostatin and glucagon secretion is mediated by these neurons. Intracellular beta-cell GABAA and its metabolism may have a role in beta-cell function. New evidence indicates that GABA shunt activity is involved in regulation of insulin secretion. In addition, GABA or its metabolites may regulate proinsulin synthesis. These new observations provide insight into the complex nature of GABAergic neurons and beta-cell GABA in regulation of islet function.
Diabetes 1991 Nov
PMID:Structural and functional considerations of GABA in islets of Langerhans. Beta-cells and nerves. 193 99

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.
 ...
PMID:Two genes encode distinct glutamate decarboxylases. 206 16

A patient who developed generalized autoimmune myasthenia gravis six years after the spontaneous remission of a stiff-man syndrome is described. He also suffered from chronic active hepatitis and had radiological evidence of a thymoma. He did not have diabetes mellitus. Besides anti-nicotinic acetylcholine receptor antibodies, anti-nuclear, anti-DNA, anti-mitochondrial and anti-skeletal muscle antibodies were found in his serum, while islet-cell antibodies were absent. Immunocytochemistry studies failed to demonstrate autoantibodies to GABA-ergic nerve terminals, although an aspecific neuronal immunostaining was observed. The clinical and immunological features of this case support the hypothesis of a dysimmune pathogenesis of SMS, also in cases not associated with autoimmunity to GABA-ergic nerve terminals. Furthermore, a relationship between thymoma and the neurological syndromes discussed could be considered.
 ...
PMID:Autoimmune myastenia gravis with thymoma following the spontaneous remission of stiff-man syndrome. 236 54

Little is known about the implication of central GABAergic neurons. However, there is evidence suggesting a growing importance of GABAergic function in the action of antidepressants. Since streptozotocin (STZ)-diabetic rats have been shown to be resistant to the action of various antidepressants, we were interested in evaluating the density of GABAergic receptor binding sites in the cortex of STZ-diabetic rats on day 15 and day 30 of diabetes. A specific and marked decrease in GABA B receptor density was observed with no change in GABA A. Although no clear relationship could be demonstrated, it may be suggested that a central GABAergic dysfunction of diabetic rats may contribute to explain their resistance to antidepressants.
 ...
PMID:Decreased central GABA B receptor binding sites in diabetic rats. 284 69


1 2 3 4 5 6 7 8 9 10 Next >>