Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated whether previously reported muscle mitochondrial dysfunction and altered gene transcript levels in type 2 diabetes might be secondary to abnormal blood glucose and insulin levels rather than an intrinsic defect of type 2 diabetes. A total of 13 type 2 diabetic and 17 nondiabetic subjects were studied on two separate occasions while maintaining similar insulin and glucose levels in both groups by 7-h infusions of somatostatin, low- or high-dose insulin (0.25 and 1.5 mU/kg of fat-free mass per min, respectively), and glucose. Muscle mitochondrial DNA abundance was not different between type 2 diabetic and nondiabetic subjects at both insulin levels, but the majority of transcripts in muscle that are involved mitochondrial functions were expressed at lower levels in type 2 diabetes at low levels of insulin. However, several gene transcripts that are specifically involved in the electron transport chain were expressed at higher levels in type 2 diabetic patients. After the low-dose insulin infusion, which achieved postabsorptive insulin levels, the muscle mitochondrial ATP production rate (MAPR) was not different between type 2 diabetic and nondiabetic subjects. However, increasing insulin to postprandial levels increased the MAPR in nondiabetic subjects but not in type 2 diabetic patients. The lack of MAPR increment in response to high-dose insulin in type 2 diabetic patients occurred in association with reduced glucose disposal and expression of peroxisome proliferator-activated receptor-gamma coactivator 1alpha, citrate synthase, and cytochrome c oxidase I. In conclusion, the current data supports that muscle mitochondrial dysfunction in type 2 diabetes is not an intrinsic defect, but instead a functional defect related to impaired response to insulin.
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PMID:Skeletal muscle mitochondrial functions, mitochondrial DNA copy numbers, and gene transcript profiles in type 2 diabetic and nondiabetic subjects at equal levels of low or high insulin and euglycemia. 1713 Apr 74

Photoperiod is an important factor of mammalian seasonal rhythm. The Harderian gland (HG) appears to act as a "standby" structure of the retinal-pineal axis, mediating light signals in vitro and neuroendocrine regulation in vivo; however, the effect of photoperiod on the HG is not clear. Here, we studied morphological differences in the HG of female striped dwarf hamsters (Cricetulus barabensis), a small mammal that experiences an annual rhythm, under different photoperiods (i.e., SP, short photoperiod; MP, moderate photoperiod; LP, long photoperiod), and further investigated the molecular mechanisms related to these morphological differences. Results showed that body weight, carcass weight, and HG weight were higher in the SP and LP groups than that in the MP group. Protein expression of hydroxyindole-o-methyltransferase, a key enzyme in melatonin synthesis, was higher in the SP group than in the other two groups. Somatostatin showed highest expression in the LP group. Furthermore, comparison of changes in the HG ultrastructure demonstrated autolysosome formation in the SP group. Protein aggregation and mRNA expression of LC3 and protein expression of LC3II/LC3I were higher in the SP group than in the MP group, indicating elevated autophagy under SP. Chromatin agglutination and mitochondrial damage were observed and bax/bcl2 and cytochrome C expression increased at the protein and mRNA levels in the SP and LP groups, suggesting increased apoptosis. Protein expression of dynamin-related protein 1 and mitochondrial fission factor (Mff) were highest in the SP group, suggesting elevated mitochondrial fission. Protein expression levels of adenosine triphosphate (ATP) synthase and citrate synthase were lower in the LP group than in the SP and MP groups. These results indicated that autophagy and apoptosis imbalance under SP and LP conditions may have led to HG weight loss and up-regulation of mitochondrial apoptosis may have weakened mitochondrial function under LP conditions. Finally, melatonin synthesis appeared to be positively correlated with the time hamsters entered darkness.
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PMID:Photoperiod Affects Harderian Gland Morphology and Secretion in Female Cricetulus barabensis: Autophagy, Apoptosis, and Mitochondria. 3243 3