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)

It has been established that adenosine, its agonists, or antagonists can cause dramatic changes in insulin sensitivity in isolated soleus muscle and, moreover, can modify changes in sensitivity caused by pathophysiological conditions. Addition of adenosine deaminase to the incubation medium, which is known to lower the concentration of adenosine, increases the sensitivity of glycolysis to insulin. Addition of an adenosine-receptor agonist decreases sensitivity by about 10-fold, whereas addition of an adenosine-receptor antagonist increases sensitivity by about 10-fold. The latter totally removes the resistance of glucose utilization to insulin in the isolated soleus muscle obtained from either the genetically obese rat or from the rat fed a high sucrose diet. These findings strongly support the view that changes in insulin sensitivity in muscle can be brought about either by acute changes in the local concentration of adenosine or in the affinity or number of receptors for adenosine in muscle. However, in many of the conditions investigated, in which insulin sensitivity in muscle is changed, there was no correlation between the change in the adenosine content of the muscle and altered insulin sensitivity. It has also been shown that prostaglandin E1 can increase dramatically the sensitivity of glycolysis to insulin and that this is a specific effect of prostaglandins of the E series. It is not produced by prostacyclins, thromboxanes, or leukotrienes. It is unclear if there is a relationship between the effects of adenosine and prostaglandins. Chronic elevation of catecholamines may increase the sensitivity of glucose utilization to insulin and also increase the rate of thermogenesis by substrate cycling.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Care 1992 Nov
PMID:Recent developments in metabolism that impinge on research into the nature and treatment of diabetes mellitus. 146 6

We report a 2.3-year-old girl with complete lack of adenosine deaminase (ADA) activity who presented with severe atopic dermatitis and insulin-dependent diabetes mellitus but only mild recurrent infections. Abnormalities of immune function included profound depletion of CD8+ lymphocytes, hyperimmunoglobulinaemia E, and very low in vitro proliferative response to mitogens. Treatment with polyethylene glycol-conjugated ADA was followed by rapid amelioration of clinical and immunological conditions. The immunological and clinical features of this child suggest that the clinical spectrum of ADA deficiency may be broader than originally supposed.
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PMID:Insulin-dependent diabetes mellitus and severe atopic dermatitis in a child with adenosine deaminase deficiency. 146 54

There are two approaches to identify diabetes-susceptibility genes. One approach is to isolate and characterize genes expressed in the beta-cell and in insulin target tissues whose mutation or altered expression may contribute to the development of diabetes mellitus. Another approach is to clone a diabetes-susceptibility gene by a reverse genetic strategy. The first step for this strategy is to identify a DNA polymorphism that is linked to the disease locus. Using the strategy of the first approach, several candidate genes were examined. Among these genes, the mutation of insulin genes and insulin receptor genes was found in the patient with diabetes. By cDNA cloning or PCR-direct sequencing methods, we identified several mutations in the insulin receptor genes of four insulin-resistant diabetic patients. At least two mutants of insulin receptor genes were expressed in Chinese hamster ovary cells and these mutated receptors showed impaired ability to transduce insulin action in these cultured cells. The expression of these mutant genes in animals such as transgenic mice will be indispensable to establish the relationship between the gene mutation and the abnormality found in the patient. Using the strategy of the second approach, Bell et al. recently reported that the gene responsible for MODY (maturity-onset diabetes of the young) is tightly linked to the adenosine deaminase gene on chromosome 20q. However, this strategy will not be applicable for identification of diabetes-susceptibility genes of NIDDM, since this disorder is likely to be genetically heterogenous, with mutations in several different genes able to cause hyperglycemia, and this heterogeneity could confound the linkage analysis.
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PMID:[Diabetes mellitus and molecular biology]. 177 65

The spontaneously diabetic BB (BBd) rat displays marked T lymphopenia. The present study was designed to investigate whether the immunodeficiency in this animal may be associated with deficiency of purine nucleoside phosphorylase (PNP) and possibly adenosine deaminase (ADA). The activities of these two enzymes were measured in lymphoid and non-lymphoid cells from both non-diabetes-prone (BBn) and BBd rats as well as from streptozotocin-induced diabetic (STZ) BBn rats. There were no significant differences between BBn and BBd rats in ADA activities in thymocytes, skeletal muscle or brain. However, ADA activity was increased (P less than 0.01) by 50% in BBd mesenteric lymph node lymphocytes and splenocytes as compared with BBn cells, but was not altered in cells from STZ-BBn rats. On the other hand, the PNP activity in BBd thymocytes was only 61% (P less than 0.01) of that observed in BBn cells. This PNP deficiency was not the consequence of diabetes per se, as its activity was normal in thymocytes from STZ-BBn rats. There were no significant differences in PNP activities between BBn and BBd rats in all other cell types examined. The diabetic BB rat may be a novel source of PNP-deficient thymocytes (mainly immature T cells) for studying biochemical mechanisms of immunodeficiency in association with decreased PNP activity. The findings also raise the question of whether a causal relationship exists between PNP deficiency and the recently demonstrated abnormality in T cell maturation in the thymus of the BBd rat.
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PMID:Deficiency of purine nucleoside phosphorylase activity in thymocytes from the immunodeficient diabetic BB rat. 183 79

Adenosine and prostaglandins of the E series inhibit lipolysis in adipocytes by binding to cell surface receptors. This inhibition is mediated via Gi. It has been reported that Gi is almost absent in livers from diabetic rats. Therefore, we have evaluated the sensitivity of adipocytes from diabetic rats to the adenosine analogue N6-phenylisopropyl adenosine (PIA) and to prostaglandin E1 (PGE1). Diabetes was induced with streptozocin (65 mg/kg i.v.), and after 7 days, adipocytes were isolated. Lipolysis (measured in the presence of adenosine deaminase) was inhibited by PIA and PGE1 in both control and diabetic cells. However, the dose-response curves were markedly shifted to the right in the cells from diabetic rats. The IC50 for PIA was 0.30 +/- 0.02 nM in controls and 0.83 +/- 0.08 in diabetic rats (P less than 0.001), and the IC50 for PGE1 was 3.16 +/- 0.18 nM in controls and 5.26 +/- 0.57 nM in diabetic rats (P less than 0.02). These findings indicate decreased sensitivity to both adenosine and PGE1. Adipocyte membranes were isolated from control and diabetic rats. Adenosine receptors (measured by binding of 125I-labeled hydroxy-PIA) were not altered in cells from diabetic rats. However, the ability of Gpp(NH)p (a nonhydrolyzable GTP analogue) to inhibit adenosine-receptor binding was markedly decreased in membranes from diabetic rats, suggesting a change at the level of Gi. The alpha-subunits of Gi1, Gi2, Gi3, and Gs were quantitated on Western blots with a series of recently characterized anti-peptide antisera. This revealed that the amounts of each of these G proteins were normal in membranes from the diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Jan
PMID:Evidence for impaired coupling of receptors to Gi protein in adipocytes from streptozocin-induced diabetic rats. 184 51

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterized by an early age of onset, usually before 25 years of age, and an autosomal dominant mode of inheritance. The largest and best-studied MODY pedigree is the RW family. The majority of the diabetic subjects in this pedigree has a reduced and delayed insulin-secretory response to glucose, and it has been proposed that this abnormal response is the manifestation of the basic genetic defect that leads to diabetes. Using DNA from members of the RW family, we tested more than 75 DNA markers for linkage with MODY. A DNA polymorphism in the adenosine deaminase gene (ADA) on the long arm of chromosome 20 was found to cosegregate with MODY. The maximum logarithm of odds (lod score) for linkage between MODY and ADA was 5.25 at a recombination fraction of 0.00. These results indicate that the odds are greater than 178,000:1 that the gene responsible for MODY in this family is tightly linked to the ADA gene on chromosome 20q.
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PMID:Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q. 189 28

After administration of insulin adenosine deaminase activity was reduced in different skeletal muscle types, the heart and the liver. On the other hand profound reduction in the plasma insulin concentration (streptozotocin diabetes) resulted in elevation of the enzyme activity in the tissues. It is concluded that the local concentration of adenosine may be effected by the concentration of insulin in the plasma.
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PMID:On the role of insulin in regulation of adenosine deaminase activity in rat tissues. 214 55

1. Adipocytes were isolated from epididymal white fat and interscapular brown fat of male rats, and activities of 5'-nucleotidase, adenosine deaminase and adenosine kinase were measured in cell extracts. 2. 5'-Nucleotidase activity in white adipocytes was increased in streptozotocin-diabetes, decreased in hypothyroidism and increased with age. That activity in brown adipocytes was unchanged in diabetes, decreased in hypothyroidism and increased with age. 5'-Nucleotidase activity was higher in white adipocytes from female rats. 3. Adenosine deaminase activity in white adipocytes was increased in diabetes, decreased in hypothyroidism and increased with age. That activity in brown adipocytes was decreased in diabetes and hypothyroidism. 4. Adenosine kinase activity in both cell types was unchanged in diabetes or hypothyroidism, but increased with age.
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PMID:Enzymes involved in adenosine metabolism in rat white and brown adipocytes. Effects of streptozotocin-diabetes, hypothyroidism, age and sex differences. 282 32

1. Adipocytes were isolated from the interscapular brown fat of male rats maintained at 21 degrees C. These animals were controls, streptozotocin-diabetics or 2-day insulin-treated diabetics. 2. With adipocytes from diabetic animals, maximum rates of noradrenaline-stimulated O2 uptake were decreased by 58%, and the Bmax. of [3H]GDP binding to mitochondria was decreased by 55%. Insulin administration reversed both of these changes. 3. Streptozotocin-diabetes increased basal lipolysis in adipocytes incubated with adenosine deaminase (1 unit/ml), decreased the EC50 (concn. giving 50% of maximum effect) for noradrenaline, but did not change the maximum rate of noradrenaline-stimulated lipolysis. Except for some small differences at very low concentrations (10-100 pM), diabetes or insulin treatment did not alter the sensitivity of noradrenaline-stimulated lipolysis or O2 uptake to the inhibitory effect of N6-phenylisopropyladenosine. It is therefore concluded that the lesion(s) in thermogenesis in diabetes are not attributable to any changes in lipolysis. 4. Blood flow through interscapular brown fat, measured by accumulation of [14C]DDT [14C-labelled 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] was increased by 2.3-fold 70 min after a single administration of insulin to diabetic rats. This treatment decreased blood flow through epididymal white fat by 58%. 5. Propranolol treatment of diabetic rats muted the ability of insulin treatment to increase the maximum rate of noradrenaline-stimulated O2 uptake, suggesting that this action of insulin may be a secondary one rather than a direct effect of the hormone on the adipocytes.
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PMID:Factors influencing the altered thermogenic response of rat brown adipose tissue in streptozotocin-diabetes. 327 24

High-performance liquid chromatography analysis of acid-extracted tissues revealed decreases of high-energy nucleotides and increases in low-energy nucleotides and metabolites in heart, diaphragm, and liver but not in kidneys of diabetic rats. In comparison with nondiabetic rats, the total adenine nucleotide content of diabetic rat heart and diaphragm but not liver decreased, indicating an increase in catabolism of AMP. Maximal initial rates of the AMP catabolic enzymes 5'-nucleotidase, adenosine deaminase, and AMP deaminase were elevated in the hearts of BB/Wistar and streptozocin-induced diabetic rats. Nucleotide salvage enzymes adenylosuccinate synthetase and adenylosuccinate lyase were elevated above normal in the diabetic heart, whereas hypoxanthine-guanine phosphoribosyl transferase was not altered. Cytosolic-to-mitochondrial ratios from maximal initial rates after correction for mitochondrial breakage were increased above controls in diabetic hearts for nucleoside diphosphokinase and aspartate aminotransferase. Nucleotide levels, degradation rates, and substrate compartmentation between cytosol and mitochondria are discussed in relation to concurrent diabetes.
Diabetes 1988 May
PMID:Adenine nucleotide metabolism in hearts of diabetic rats. Comparison to diaphragm, liver, and kidney. 336 Feb 19


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