Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium butyrate is widely used to differentiate insulinoma cell lines. However, sodium has been shown to decrease glucose phosphorylation in the liver and heart and decrease the expression of glucose transporter. Since these mechanisms are essential for glucose-induced insulin secretion, the ultimate function of the pancreatic beta-cell, we investigated the effect of sodium butyrate on both glucose-phosphorylating enzymes as well as glucose transport in the pancreatic cell line RIN-m5F. Treatment of RIN-m5F cells with 2.5 mM sodium butyrate for 72 h increased by twofold both hexokinase and glucokinase (GK) activities, as well as the gene expression of GK. Sodium butyrate treatment had no effect on GLUT-1 mRNA levels but increased the GLUT-2 mRNA 3.7-fold. Kinetic analysis of 2-deoxyglucose transport displayed a single curve with Km = 1.2 mM and Vmax = 10.9 pmol/micrograms protein/min in the untreated cells, values similar to the low Km glucose transport reported in the pancreatic beta-cells. This low Km transport component markedly decreased with sodium butyrate treatment, and interestingly a second component with a higher Km appeared, consistent with the increase in GLUT-2 mRNA. We conclude that the differentiating action of sodium butyrate involves increases in GK and GLUT-2 gene expression, which characterizes the differentiated state of the pancreatic beta-cell. However, the inhibitory effect of sodium butyrate on low Km glucose transport needs to be considered in the use of this compound to promote differentiation.
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PMID:Effect of sodium butyrate on glucose transport and glucose-phosphorylating enzymes in RIN-m5F cells. 830 95

RINm5F insulinoma cells show a defective physiological insulin secretory response to glucose stimulation. The short chain carbonic acid sodium butyrate induced a growth arrest during a 72-h tissue culture period. In contrast to control RINm5F cells, 2 mM glucose increased insulin secretion by more than 70% in these sodium butyrate-treated cells (1 mM) without any further increase of the secretory rate between 2 and 20 mM glucose. This effect of sodium butyrate on insulin secretion was assessed in comparison with its effect on gene expression of the GLUT1 and GLUT2 glucose transporter, hexokinase type I and type II, glucokinase and insulin. Sodium butyrate at a 1 mM concentration decreased GLUT1 gene expression by nearly 50%, but did not induce gene expression of the low-affinity GLUT2 glucose transporter above the detection limit. Furthermore, sodium butyrate increased glucokinase gene expression by more than 50% and hexokinase type II gene expression by more than 100%, while insulin gene expression was increased only by 24%. Hexokinase type II enzyme activity was increased by more than 100% without a concomitant significant change of the glucokinase enzyme activity. Sodium butyrate (2 mM) caused effects comparable with those of 1 mM sodium butyrate. Thus the improved insulin secretory responsiveness of RINm5F insulinoma cells after sodium butyrate treatment at low non-physiological millimolar glucose concentrations can be interpreted as a result of an increased hexokinase-mediated metabolic flux rate through the glycolytic chain.
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PMID:Effects of sodium butyrate on glucose transporter and glucose-phosphorylating enzyme gene expression in RINm5F insulinoma cells. 886 83

In the present study, the potential effects of 2-allyl amino 4-methyl sulfanyl butyric acid (AMSB) on the glucose metabolism and glycoprotein components in streptozotocin (STZ) induced experimental diabetic rats were determined. Further, molecular modeling was performed to investigate the modes of AMSB interaction with insulin receptor active sites. The blood glucose and plasma insulin levels were measured in the STZ induced diabetic rats, whereas the glucose metabolism and glycoprotein components were analyzed from the plasma and tissues. After oral treatment of AMSB there was a significant reduction in blood glucose, glucose-6-phosphatase, fructose-1,6-bisphosphatase and glycogen phosphorylase. On the other hand, the activity of the glycoprotein levels, such as hexose, hexosamine, fucose and sialic acid, were significantly reduced. In addition, a significant elevation in plasma insulin, hexokinase, glycogen and glycogen synthase were also observed in the AMSB treated rats. The molecular modeling study revealed that AMSB has a stable binding pattern to the active site of insulin, with a Gscore value of -7.34 Kcal mol-1. From this study we conclude that AMSB has a potent antidiabetic activity in addition to its protective effect on glycoprotein metabolism.
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PMID:Beneficial protective effects of 2-allyl amino 4-methyl sulfanyl butyric acid on glucose metabolism and glycoprotein components in streptozotocin induced diabetic rats with molecular modeling. 3009 Mar 55