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

The effect of glucose on lipolytic regulation was studied in isolated human adipocytes. Glucose enhanced adipocyte glycerol release in the presence and absence of the beta-adrenergic agent ritodrine by 150-200% of control rates. The glucose effect was maximal at just greater than 1 mM glucose and could not be attributed to prevention of a time-dependent decline in lipolysis. Glucose not only increased lipolytic stimulation at each of several concentrations of ritodrine but also enhanced the sensitivity to stimulation at low concentrations of the agent. Ritodrine-stimulated lipolysis was inhibited by insulin by 50-60%; although glucose increased absolute rates of lipolysis, it did not affect the relative inhibition of lipolysis by insulin or the sensitivity to the hormone. In investigating a possible cause of the glucose effect on lipolysis, it was found that the addition of adenosine deaminase increased lipolytic rates in the absence of glucose and blunted the relative stimulation of lipolysis by glucose, the latter implicating extracellular adenosine in the mechanism of the glucose effect.
Diabetes 1986 Jul
PMID:Potentiation by glucose of lipolytic responsiveness of human adipocytes. 372 Oct 62

Opposing changes were discovered in the liver and blood of rats aged 1-1 1/2 months with alloxan diabetes as regards the content of adenine, xanthine plus guanine, uric acid and the activity of adenine-, adenosine-, guanine deaminase and 5'-nucleotidase. The ratio of the activity of adenosine deaminase to that of 5'-nucleotidase correlating with the level of glycemia might be the most informative test in the diagnosis of the depth of the discovered metabolic disorders in alloxan diabetes.
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PMID:[Characteristics of purine and nucleotide metabolism in juvenile rats with alloxan diabetes]. 664 35

Maturity-onset diabetes of the young (MODY) is a model for genetic studies of non-insulin-dependent diabetes mellitus. We have identified 15 MODY families in which diabetes is not the result of mutations in the glucokinase gene. This cohort of families will be useful for identifying other diabetes-susceptibility genes. Nine other candidate genes potentially implicated in insulin secretion or insulin action have been tested for linkage with MODY in these families, including glucokinase regulatory protein, hexokinase II, insulin receptor substrate 1, fatty acid-binding protein 2, glucagon-like peptide-1 receptor, apolipoprotein C-II, glycogen synthase, adenosine deaminase (a marker for the MODY gene on chromosome 20), and phosphoenolpyruvate carboxykinase. None of these loci showed evidence for linkage with MODY, implying that mutations in these genes do not make a major genetic contribution to the development of MODY. In addition to these linkage analyses, one or two affected subjects from each family were screened for the presence of the A to G mutation at nucleotide 3,243 of the mitochondrial tRNA(Leu(UUR)) gene. This mutation was not found in any of these subjects. Finally, we report the localization of the gene encoding the regulatory protein of glucokinase to chromosome 2, band p22.3 and the identification of a restriction fragment length polymorphism at this locus.
Diabetes 1994 Mar
PMID:Search for a third susceptibility gene for maturity-onset diabetes of the young. Studies with eleven candidate genes. 750 74

The dose response effect of a new adenosine analogue, GR79236 (N-[1S trans-2-hydroxycyclopentyl] adenosine) upon insulin sensitivity was examined in human adipocytes. The influence of adenosine upon insulin sensitivity for suppression of lipolysis and stimulation of glucose transport was examined. Removal of adenosine by use of adenosine deaminase stimulated lipolysis to the same extent as did 10(-9) M noradrenaline. GR79236 brought about dose dependent inhibition of lipolysis with half-maximal effect at 11.3 +/- 7.8 x 10(-9) M. When lipolysis was stimulated by noradrenaline alone the subsequent inhibition of lipolysis brought about by GR79236 was significantly greater than that of insulin. To examine adenosine effects on the insulin signalling pathway separately from those on lipolysis, the insulin sensitivity of glucose transport was examined. Removal of adenosine brought about a small but significant increase in the concentration of insulin required for half-maximal stimulation of glucose transport. Adenosine agonists offer promise as new agents for the modulation of metabolism in diabetes and other states of insulin resistance.
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PMID:Adenosine effects upon insulin action on lipolysis and glucose transport in human adipocytes. 762 86

We report a patient with a clinical picture consisting of small birth weight, connatal hypoplastic anaemia, vacuolised bone marrow precursors, failure to thrive, and, subsequently, by insulin-dependent diabetes, renal Fanconi syndrome, lactic acidosis, complex organic aciduria, and elevation of haemoglobin F and of adenosine deaminase activity. The clinical course was progressive and death occurred at age 19 months. A high proportion of mitochondrial (mt) DNA molecules with a deletion of nucleotides 9238 to 15575 were identified in several tissues; about half of the shortened mtDNA molecules were concatenated to form circular dimers. The clinical and laboratory findings support recent conclusions that Pearson syndrome is not confined to bone marrow and pancreas, as originally described, but is a multi-organ disorder associated with deletions in part of the mtDNA molecules. The tissue distribution and the relative proportions of the abnormal mtDNA molecules apparently determine the phenotype and clinical course.
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PMID:Pearson bone marrow-pancreas syndrome with insulin-dependent diabetes, progressive renal tubulopathy, organic aciduria and elevated fetal haemoglobin caused by deletion and duplication of mitochondrial DNA. 768 Mar 15

Mutations of the glucokinase gene (chromosome 7p) have been shown to cause some cases of familial maturity onset diabetes of youth (MODY) but few, if any, cases of late onset familial Type 2 diabetes. A further single large pedigree with MODY has shown linkage to a marker for the adenosine deaminase gene (ADA, chromosome 20q), although the diabetes susceptibility gene at this locus has not been identified. We have studied members of 19 families with familial Type 2 diabetes (including 10 European families, 6 families from the Indian subcontinent, and 3 families of Afro-Caribbean origin), 2 of which were of MODY type (and both European), with a glucokinase marker and a marker linked to ADA, to examine whether glucokinase, or the unknown defect on chromosome 20, are implicated in diabetes in our pedigrees. Several models were constructed for standard two-point linkage analysis. Glucokinase is not the cause of diabetes in all of these families but was excluded in only one MODY family. It was possible to exclude both loci in the second MODY pedigree. No evidence was found of linkage to either marker in this multi-ethnic population under the models used. At least one further locus is involved in determining susceptibility to MODY.
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PMID:Genetic analysis of glucokinase and the chromosome 20 diabetes susceptibility locus in families with type 2 diabetes. 770 22

To investigate the possible contribution of glucokinase (GCK) and adenosine deaminase (ADA) loci to the genetic susceptibility to type 2 (non-insulin-dependent) diabetes mellitus, we studied the association of these loci with type 2 diabetes in the Japanese population. Fifty patients with type 2 diabetes and 50 control subjects were analyzed for microsatellite polymorphism 3' to the GCK gene and PstI polymorphism in the ADA gene by polymerase chain reaction. The frequency of the most common GCK allele (Z) was significantly lower in type 2 diabetic patients than that in control subjects and a longer Z + 2 allele was more common in type 2 diabetic patients (26% vs. 15%, P = 0.053), particularly in those with younger age of onset (33% vs. 15%, younger onset type 2 diabetes vs. control, P = 0.014). The frequency of genotypes containing at least one Z + 2 allele was significantly more common in type 2 diabetic patients (46% vs. 28%, P < 0.05), particularly in those with younger age of onset (61% vs. 28%, relative risk 4.00, P < 0.01). In contrast, there was no difference in allelic or genotypic frequencies of PstI polymorphism in the ADA gene between the two groups. Despite the association between the GCK locus and type 2 diabetes, none of the patients had known mutations (Glu265-->AM265, Glu279-->AM279, Gly299-->Arg299, Glu300-->Gln300, Leu309-->Pro309). These results suggest that the GCK locus, but not the ADA locus, contributes to the genetic susceptibility to type 2 diabetes in Japanese.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1994 Apr
PMID:Early-onset type 2 (non-insulin-dependent) diabetes mellitus is associated with glucokinase locus, but not with adenosine deaminase locus, in the Japanese population. 792 73

We performed limiting dilution culture of T cells from a patient affected by primary immunodeficiency as a result of complete lack of adenosine deaminase (ADA) activity and also affected by insulin-dependent diabetes mellitus (type I diabetes). Despite the occurrence of immunodeficiency, we were able to raise and grow T cell clones derived from this patient in long-term culture. These T cells displayed ADA enzymatic activity and produced interleukin-2 after engagement of their T cell receptor (TCR)/CD3 complex. We analyzed the TCR repertoire of such clones by nucleotide sequencing of TCR beta chains. The results show that the T cell clones express different V beta but similar J regions. However, the CDR3 regions which are implicated in antigen recognition were found to be heterogeneous.
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PMID:Long-term culture and T cell receptor analysis of T cell clones isolated from a patient with adenosine deaminase deficiency and type I diabetes. 795 66

The effect of the adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (dCF) on the development of insulin-dependent diabetes mellitus (IDDM) was assessed in the BB Wistar rat. Sixty-one male rats were treated from days 30 to 120 with 0, 0.5, 1.0 or 1.5 mg dCF/kg/week. The incidence of IDDM was 78% in the controls and was significantly (P < 0.01) decreased in rats receiving 1.5 mg dCF/kg/week (32%), but not in rats receiving lower doses of the drug. However, for those rats that became diabetic the mean time to the development of IDDM was unchanged in animals receiving dCF compared with control. dCF treatment did not produce significant weight loss in the animals or gross changes in the thymus, spleen or kidneys. Although the protective effect of dCF against IDDM was likely produced by immunosuppression, the different dCF dosages had similar effects on ADA suppression in spleen or thymus and on dATP accumulation in these organs.
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PMID:Prevention of insulin-dependent diabetes mellitus by 2'-deoxycoformycin in the BB Wistar rat. 821 50

A typical clinical feature of patients with fasting hyperglycemia in diabetes is well correlated with accelerated hepatic glucose production which is determined by elevated FFA-induced gluconeogenesis. Therefore, to treat fasting hyperglycemia, inhibition of both FFA release and fatty acid oxidation in the liver may be efficient modalities of treatment. (1) Inhibitor of FFA release: a novel selective adenosine A1 agonist, SDZ WAG 994 is a potent inhibitor of adenosine deaminase-induced lipolysis. Twenty-three-week old, male GK rats showing glucose intolerance were treated with WAG 994 (1000 micrograms/kg body weight) for 16 days. Plasma glucose level at 0 time in WAG group was significantly (P < 0.01) less than that of the control. Both plasma FFA and triglyceride concentrations also decreased by 54% and 74%, respectively (vs. control GK rats). (2) Inhibition of hepatic fatty acid oxidation: beta-aminobetaine (emeriamine) is a water-soluble carnitine analog and inhibition of CPT-1 in isolated hepatocytes is 100 times more sensitive than that in isolated cardiocytes and it suppresses both gluconeogenesis and ketogenesis by 60-80%. However, it may be possible that this drug may induce fat deposition in the liver. An inhibitor of elevated fatty acid release from adipose tissue in concomitant with liver-specific and reversible inhibition of fatty acid oxidation may be an effective agent with hypoglycemic and hypolipidemic action for the treatment of diabetes mellitus.
Diabetes Res Clin Pract 1995 Aug
PMID:Rationale and hurdles of inhibitors of hepatic gluconeogenesis in treatment of diabetes mellitus. 852 14


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