Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enzymatic systems of hepatic hyperlipogenesis supply by substrate (acetyl-CoA) and cofactors (NADPH and ATP) were studied in experiments on diabetic C57Bl/Ks J mice (db/db) that served as a model of non-insulin dependent diabetes. The rise in acetyl-CoA synthetase activity catalyzing the primary step of lipogenesis from acetate has been found, while pyruvate dehydrogenase complex activity did not differ from the control and ATP-citrate lyase activity was lowered. Hyperlipogenesis in non-insulin dependent diabetes was induced by the activation of cellular energy supply revealed in enhanced 2-oxoglutarate dehydrogenase activity and elevated ATP level, as well as changes in the activity ratio of NADPH supply and utilization and the rise in fructose-1,6-diphosphate, allosteric effector of fatty acid synthetase, which resulted in the increase of the enzyme activity and created wider potentials of NADPH utilization as a reducing equivalent in lipogenesis.
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PMID:[Enzyme systems of the substrate and cofactor supply of hyperlipogenesis in non-insulin-dependent diabetes]. 289 64

The advent of hyperpolarized (13)C magnetic resonance (MR) has provided new potential for the real-time visualization of in vivo metabolic processes. The aim of this work was to use hyperpolarized [1-(13)C]pyruvate as a metabolic tracer to assess noninvasively the flux through the mitochondrial enzyme complex pyruvate dehydrogenase (PDH) in the rat heart, by measuring the production of bicarbonate (H(13)CO(3)(-)), a byproduct of the PDH-catalyzed conversion of [1-(13)C]pyruvate to acetyl-CoA. By noninvasively observing a 74% decrease in H(13)CO(3)(-) production in fasted rats compared with fed controls, we have demonstrated that hyperpolarized (13)C MR is sensitive to physiological perturbations in PDH flux. Further, we evaluated the ability of the hyperpolarized (13)C MR technique to monitor disease progression by examining PDH flux before and 5 days after streptozotocin induction of type 1 diabetes. We detected decreased H(13)CO(3)(-) production with the onset of diabetes that correlated with disease severity. These observations were supported by in vitro investigations of PDH activity as reported in the literature and provided evidence that flux through the PDH enzyme complex can be monitored noninvasively, in vivo, by using hyperpolarized (13)C MR.
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PMID:In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance. 1868 83

Leptin treatment reverses hyperglycemia in animal models of poorly controlled type 1 diabetes (T1D), spurring great interest in the possibility of treating patients with this hormone. The antidiabetic effect of leptin has been postulated to occur through suppression of glucagon production, suppression of glucagon responsiveness or both; however, there does not appear to be a direct effect of leptin on the pancreatic alpha cell. Thus, the mechanisms responsible for the antidiabetic effect of leptin remain poorly understood. We quantified liver-specific rates of hepatic gluconeogenesis and substrate oxidation in conjunction with rates of whole-body acetate, glycerol and fatty acid turnover in three rat models of poorly controlled diabetes, including a model of diabetic ketoacidosis. We show that the higher rates of hepatic gluconeogenesis in all these models could be attributed to hypoleptinemia-induced activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in higher rates of adipocyte lipolysis, hepatic conversion of glycerol to glucose through a substrate push mechanism and conversion of pyruvate to glucose through greater hepatic acetyl-CoA allosteric activation of pyruvate carboxylase flux. Notably, these effects could be dissociated from changes in plasma insulin and glucagon concentrations and hepatic gluconeogenic protein expression. All the altered systemic and hepatic metabolic fluxes could be mimicked by infusing rats with Intralipid or corticosterone and were corrected by leptin replacement. These data demonstrate a critical role for lipolysis and substrate delivery to the liver, secondary to hypoleptinemia and HPA axis activity, in promoting higher hepatic gluconeogenesis and hyperglycemia in poorly controlled diabetes.
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PMID:Leptin reverses diabetes by suppression of the hypothalamic-pituitary-adrenal axis. 2499 39

Short-chain fatty acids (SCFAs) are mainly generated by bacterial fermentation of non-digestible carbohydrates such as dietary fiber. In the last decade, new investigations have revealed that SCFAs have a very specific function and serve as active microbial metabolites, which are able to modulate the function of immune cells in the intestine and other tissues. Recent studies have highlighted the immunomodulatory potential of SCFAs in several autoimmune and inflammatory disorders such as multiple sclerosis, colitis, type 1 diabetes and rheumatoid arthritis. While the SCFA-mediated activation of GPR41/GPR43 signalling pathways and their inhibitory activity on histone deacetylases have been extensively investigated, the impact of SCFAs on the T cell metabolism is poorly understood. SCFAs induce metabolic alterations in T cells by enhancing the activity of the mTOR complex and by regulating their glucose metabolism. Once taken up into T lymphocytes, SCFA-derived acetyl groups contribute to the cellular acetyl-CoA pool, which influences the histone acetylation and cytokine gene expression. This article reviews how SCFAs modulate the metabolic status of T cells, thereby impacting on epigenetic modifications and T cell function. We will also discuss how the recent findings from SCFA biology might be utilized for potential immune therapies of various autoimmune diseases.
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PMID:Short-chain fatty acids: Bacterial messengers modulating the immunometabolism of T cells. 3105 54

The N-acetylaspartate network begins in neurons with N-acetylaspartate production catalyzed by aspartate N-acetyltransferase from acetyl-CoA and aspartate. Clinical studies reported a significant depletion in N-acetylaspartate brain level in type 1 diabetic patients. The main goal of this study was to establish the impact of either hyperglycemia or oxidative stress on the N-acetylaspartate network. For the in vitro part of the study, embryonic rat primary neurons were treated by using a nitric oxide generator for 24 h followed by 6 days of post-treatment culture, while the neural stem cells were cultured in media with 25-75 mM glucose. For the in vivo part, male adult Wistar rats were injected with streptozotocin (65 mg/kg body weight, ip) to induce hyperglycemia (diabetes model) and euthanized 2 or 8 weeks later. Finally, the biochemical profile, NAT8L protein/Nat8l mRNA levels and enzymatic activity were analyzed. Ongoing oxidative stress processes significantly affected energy metabolism and cholinergic neurotransmission. However, the applied factors did not affect the N-acetylaspartate network. This study shows that reduced N-acetylaspartate level in type 1 diabetes is not related to oxidative stress and that does not trigger N-acetylaspartate network fragility. To reveal why N-acetylaspartate is reduced in this pathology, other processes should be considered.
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PMID:Neither Excessive Nitric Oxide Accumulation nor Acute Hyperglycemia Affects the N-Acetylaspartate Network in Wistar Rat Brain Cells. 3319 75