Hepatic Hexokinase Research Articles

Antihyperglycemic effect of aqueous and ethanolic extracts of Gongronema latifolium leaves on glucose and glycogen metabolism in livers of normal and streptozotocin-induced diabetic rats

The present study was designed to investigate the antihyperglycemic effects of aqueous and ethanolic extracts from Gongronema latifolium leaves on glucose and glycogen metabolism in livers of non-diabetic and streptozotocin-induced diabetic rats. To investigate the effects of aqueous or ethanolic leaf extracts of G. latifolium, non-diabetic and STZ diabetic rats were treated twice daily (100 mg/Kg) for two weeks. Diabetic rats showed a significant decrease in the activities of hepatic hexokinase (HK), phosphofructokinase (PFK) and glucose-6-phosphate dehydrogenase (G6PDH) and an increase in glucokinase (GK) activity. The levels of hepatic glycogen and glucose were also increased in diabetic rats. However, there were no significant differences in the activities of glucose-6-phosphatase (G6Pase) in treated and untreated diabetic rats. The ethanolic extract significantly increased the activities of HK (p < 0.01), PFK (p < 0.001) and G6PDH (p < 0.01) in diabetic rats, decreased the activity of GK (p < 0.05) and the levels of hepatic glycogen (p < 0.01) and both hepatic (p < 0.001) and blood glucose (40%). The aqueous extract of G. latifolium was only able to significantly increase the activities of HK and decrease the activities of GK but did not produce any significant change in the hepatic glycogen and both hepatic and blood glucose content of diabetic rats. Our data show that the ethanolic extract from G. latifolium leaves has antihyperglycemic potency, which is thought to be mediated through the activation of HK, PFK, G6PDH and inhibition of GK in the liver. The ethanolic extract is under further investigation to determine the chemical structure of the active compound(s) and its/their mechanism of action.

Effect of cogent db, a herbal drug, on plasma insulin and hepatic enzymes of glucose metabolism in experimental diabetes.

The present study was designed to investigate the effect of cogent db, a polyherbal drug on blood glucose, plasma insulin and the activities of hepatic glucose metabolic enzymes in alloxan-induced diabetic rats. Male Wistar rats body weight of 180-200 g (six normal and 18 diabetic rats) were used in this study. The rats were divided into four groups after the induction of alloxan diabetes. In the experiment, six rats were used in each group: Group 1, normal rats given 2 ml of saline; Group 2, diabetic control rats given 2 ml of saline; Group 3, diabetic rats given aqueous solution of cogent db (0.45 g/body kg weight); and Group 4, diabetic rats given aqueous solution of glibenclamide (600 micro g/kg body weight). The treatment was given for 40 days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and the activities of hepatic glucose metabolic enzymes were determined in normal and experimental animals. Treatment with cogent db resulted in a significant reduction in blood glucose and the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of plasma insulin and hepatic hexokinase activity were significantly increased in alloxan-diabetic rats. The present investigation suggests that cogent db controls the blood glucose level by increasing glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is possible because it regulates the activities of hepatic glucose metabolic enzymes.

Utilization of glucose and starch by the grouper Epinephelus malabaricus at 23oC

: The aim of the present study was to investigate carbohydrate utilization by the grouper Epinephelus malabaricus reared at 23°C. Two isoenergetic semipurified diets were prepared with two carbohydrate sources (glucose and starch). Each diet was fed to triplicate groups of grouper in a recirculating rearing system for 8 weeks. Water temperature was held constant by a thermal controller at 23 ± 1°C. Weight gain, feed efficiency (FE) and protein efficiency ratio (PER) of fish fed the starch diet were significantly higher (P < 0.05) than those of fish fed the glucose diet. Body lipid content of the starch-fed group of fish was higher than that of glucose-fed group of fish. Hepatic hexokinase and glucose-6-phosphate dehydrogenase activities were higher in fish fed the starch diet than fish fed the glucose diet. Fish fed the glucose diet had higher hepatic glucose-6-phosphatase activity than fish fed the starch diet. These results suggest that starch is better utilized by grouper than glucose when the water temperature is 23°C.

Effect of Coccinia indica on Blood Glucose, Insulin and Key Hepatic Enzymes in Experimental Diabetes

Administration of Coccinia indica leaf extract to normal and streptozotocin diabetic animals exhibited significant hypoglycemic and antihyperglycemic effect and reversed biochemical complications. Oral administration of 200mg/ kg of ethanol extract of Coccinia indica leaves (CLEt) to diabetic animals for 45 days resulted in a significant reduction in blood glucose, glycosylated haemoglobin and an increase in total haemoglobin and plasma insulin. Similarly, the administration of CLEt to normal animals resulted in a significant hypoglycemic effect. The activities of hepatic hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and glucose-6-phosphate dehydrogenase, a lipogenic enzyme, were measured in the liver of normal, diabetic, normal rats separately treated with CLEt and glibenclamide, and diabetic rats treated separately with CLEt and glibenclamide. The activities of the lipogenic enzyme and hexokinase were significantly decreased, whereas the activities of gluconeogenic enzymes were significantly increased in the diabetic liver. Both CLEt and glibenclamide were able to restore the altered enzyme activities to almost control levels. CLEt was more effective than glibenclamide. The results indicate that the administration of CLEt to diabetic animals normalizes blood glucose and causes marked improvement of altered carbohydrate metabolic enzymes during diabetes.

Carbohydrate utilization and its protein-sparing effect in diets for grouper(Epinephelus malabaricus)

AbstractTo investigate the utilization of different carbohydrate sources and the possible protein-sparing effects of carbohydrates for grouper (Epinephelus malabaricus), six isoeneregtic purified diets were prepared. Three dietary protein levels (500, 460, 420 g/kg) were achieved by substitution with three levels (143, 195, 246 g/kg) and two sources (glucose and starch) of dietary carbohydrate. Each of the six diets was given to triplicate groups of grouper in a recirculating rearing system for 8 weeks. In the glucose group, weight gain of fish decreased with increasing dietary glucose and decreasing protein content. In the starch group, weight gain of fish given the 500 g/kg protein diet was higher (P&lt; 0 ·05) than fish given the 460 and 420 g/kg protein diets. At each of the dietary protein levels weight gain of the glucose-group fish and the starch-group fish were similar (P&gt; 0·05). At the 500 g/kg dietary protein level body lipid content of the starch-group fish was higher than that of glucose-group fish. At 500 and 460 g/kg dietary protein levels, fish given starch diets had higher hepatic hexokinase activity than fish given the glucose diets. These results suggest that, at the levels studies, the utilization of starch and glucose by grouper is similar. Decreasing the dietary protein level from 460 g/kg to 420 g/kg by increasing the starch content in the diet from 195 g/kg to 246 g/kg did not reduce (P&gt; 0·05) weight gain and food efficiency, suggesting that starch could spare some protein when the dietary protein level is low.

Hypoglycaemic and other related actions of Tinospora cordifolia roots in alloxan-induced diabetic rats

Tinospora cordifolia is widely used in Indian Ayurvedic medicine for treating diabetes mellitus. Oral administration of an aqueous T. cordifolia root extract (TCREt) to alloxan diabetic rats caused a significant reduction in blood glucose and brain lipids. The extract caused an increase in body weight, total haemoglobin and hepatic hexokinase. The root extract also lowers hepatic glucose-6-phosphatase and serum acid phosphatase, alkaline phosphatase, and lactate dehydrogenase in diabetic rats. Thus TCREt has hypoglycaemic and hypolipidaemic effect.

Effect ofSyzigium cumini extracts on hepatic hexokinase and glucose-6-phosphatase in experimental diabetes

Syzigium cumini commonly known as Jamun, is widely used in Indian folk medicine for the treatment of diabetes. Oral administration of 2.5 g/kg body weight of the aqueous extract of Jamun seed for 1 month resulted in an increase in the activity of hexokinase and a decrease in the activity of glucose-6-phosphatase in the liver of alloxan dosed diabetic animals. The results also show that there was a decrease in the leakage of acid phosphatase, alkaline phosphatase and lactate dehydrogenase in the serum of these animals. The effect exerted by Jamun seed was more prominent than that of glibenclamide. © 1997 John Wiley & Sons, Ltd.

Effect of Syzigium cumini extracts on hepatic hexokinase and glucose-6-phosphatase in experimental diabetes

Effect of Syzigium cumini extracts on hepatic hexokinase and glucose-6-phosphatase in experimental diabetes

Effects of salinity and nutritional status on growth and metabolism of Spams sarba in a closed seawater system

A re-circulating seawater system employing biological filtration was set up to assess the growth potential of sea bream ( Sparus sarba) under the combined effects of salinity (7, 15, 35 p.p.t.) and dietary protein level (30, 35, 40, 45, 50, 55%). The re-circulating system was able to sustain growth of sea bream at high stocking density (3 g 1 −1), possibly by minimising stress. Typical stress indices such as serum cortisol, glucose and lactate levels were reduced in sea bream cultured within the recirculating system. Growth rates and protein efficiency ratios of sea bream cultured at 15 p.p.t. were consistently higher than those at other salinities. Growth enhancement at 15 p.p.t. was accompanied by a reduction in oxygen consumption, ammonia excretion rates, liver lipid levels and hepatic glucose-6-phosphatase activity. However, hepatic hexokinase activity was stimulated at 15 p.p.t. Most of these effects were more evident in fish fed high protein levels. These data suggest that growth enhancement at 15 p.p.t. may be explained by (1) reduction of metabolic cost of osmoregulation, and (2) reorganisation of metabolism, which would allow protein sparing in favour of a shift towards preferential utilisation of carbohydrate and lipid.

Hepatic enzyme adaptation to different dietary carbohydrates in juvenile tilapiaOreochromis niloticus xO. aureus

The influence of two carbohydrates, starch and glucose, on hepatic enzyme activities of juvenile tilapia,Oreochromis niloticus xO. aureus, were investigated. Fish were fed either starch or glucose diet solely for 12 weeks or fed either starch or glucose diet for the first 6 weeks and then switched the diet each other for the last 6 weeks. Fish fed only the starch diet gained more (p < 0.05) body weight, had better feed conversion, higher protein deposition and energy retention values than fish fed the glucose diet. These parameters generally decreased in fish when the starch diet was fed first and then switched to the glucose diet, or increased in fish when the glucose diet was fed first and then switched to the starch diet. The starch - fed fish had higher body lipid content than glucose - fed fish. Body lipid decreased in fish transferred from the starch to glucose diet orvice versa when fish were transformed from the glucose to the starch diet. Hepatic hexokinase, phosphofructokinase, and glucose-6-phosphatase activities in fish were not affected by the different dietary regimes. Malic enzyme (ME), glucose-6-phosphate dehydrogenase (G-6-PD) and phosphogluconate dehydrogenase (PGD) activities were higher in the fish fed the starch diet than in those fed the glucose diet. Changing the diet from starch to glucose decreased ME, G-6-PD and PGD activities, whereas, changing the diet from the glucose to the starch increased these enzyme activities in fish liver. These results suggest that lipogenic enzyme activity can adapt to dietary carbohydrates in the fish liver.

Polysaccharides in fungi. XXXIII. Hypoglycemic activity of an acidic polysaccharide (AC) from Tremella fuciformis

Glucuronoxylomannan (AC) from the fruiting bodies of Tremella fuciformis exhibited a significant dose-dependent hypoglycemic activity in normal mice and also showed a significant activity in streptozotocin-induced diabetic mice, by intraperitoneal (i.p.) administration. The activities of AC-derivatives such as a product of AC which side chains had been removed were lower than that of native AC. AC raised the plasma insulin level in normal mice. Administration of AC to normal mice significantly increased the activities of hepatic hexokinase and glucose-6-phosphatase dehydrogenase, but it decreased that of hepatic glucose-6-phosphatase. Furthermore, AC reduced the glycogen content in the liver, increased the total lipid in epididymal adipose tissue, and lowered the plasma cholesterol level. The foregoing results indicated that the hypoglycemic activity of AC in normal mice was at least responsible for the increase of insulin secretion and for the acceleration of glucose metabolism. Single oral administration at a dose of 50-300 mg/kg of AC did not affect the plasma glucose level in normal mice, but continuous oral administrations of the AC solution (0.75 g/l) instead of water for a long time was found to be effective on the plasma glucose level in both experiments of the mice injected once i.p. with streptozotocin (170 mg/kg) at 0 d of AC administration and streptozotocin-induced diabetic mice.

D-Glucose transport activities in erythrocytes and hepatocytes of dogs, cats and cattle

1. 1. The activities of d-glucose transport and hexokinase were investigated in erythrocytes or hepatocytes of dogs, cats and cattle. 2. 2. The mean d-glucose transport activity in erythrocytes of dogs was 6.0 nmol/min/mg protein, half the value of hepatocytes. 3. 3. The activities of d-glucose transport in erythrocytes and hepatocytes or hepatic hexokinase of cats were about one-third of those of dogs. 4. 4. Cattle with low blood glucose concentrations showed considerably low activities of d-glucose transport and hexokinase, about one-third of those of dogs.

Insulin and glucagon family peptides in relation to activities of hepatic hexokinase and other enzymes in fed and starved Atlantic salmon ( Salmo salar) and cod ( Gadus morhua)

1. 1. Plasma levels of insulin, glucagon, and glucagon-like peptide (Glp) were all reduced by starvation of salmon and cod. In the salmon the drop in Glp was larger than in insulin and glucagon. 2. 2. After starvation the activity of hexokinase (EC 2.7.1.1) was increased in salmon liver, but decreased in cod liver. The salmon hepatic hexokinase activity was inversely correlated with the Glp/insulin ratio. 3. 3. Activities of hepatic glycogen phosphorylase (EC 2.4.1.1) and phosphofructokinase (EC 2.7.1.11) were increased in starved as compared to fed salmon. In cod, starvation resulted in decreased or unchanged activity of phosphorylase. This discrepancy may be related to different degrees of environmental and handling stress. 4. 4. Intraperitoneal injection of human insulin in salmon gave increased hepatic phosphorylase and hexokinase activities and reduced plasma levels of glucagon, Glp and endogenous fish insulin at sampling after 30 hr. 5. 5. No differences in hepatic hexokinase activities or plasma hormone levels were observed between cod fed low and high carbohydrate diets. Apparently, regulation of glucose phosphorylation by dietary carbohydrate does not occur.

High stocking density alters the energy metabolism of brook charr, Salvelinus fontinalis

Brook charr reared for 30 days at a high stocking density (120 kg/m 3) had significantly lower final body weight and reduced food consumption when compared to fish reared at a lower stocking density (30 kg/m 3). There was no effect of stocking density on plasma cortisol and T3 concentrations, while plasma T4 concentration was lowered in fish held at high stocking density. Plasma glucose levels, liver glycogen content and hepatosomatic index were significantly lower in fish reared at high stocking density, while plasma protein and free fatty acid (FFA) levels were not significantly different between groups. There were significantly higher activities of hepatic phosphofructokinase, fructose biphosphatase, 3-hydroxyacyl CoA dehydrogenase, glycerol kinase and glycerol-3-phosphate dehydrogenase in fish held at high stocking density compared with those at low stocking density. Hepatic hexokinase and glucose-6-phosphate dehydrogenase activities were significantly lower in fish at high stocking density compared with those at low stocking density, while there were no differences in pyruvate kinase, glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, glutamate dehydrogenase, glutamate pyruvate transaminase and glutamate oxaloacetate transaminase between the groups. These results suggest that high stocking density has the effect of mobilizing triglyceride sources, promoting gluconeogenesis from glycerol, but has little effect on protein metabolism.

Thioacetamide-induced changes in hepatic hexokinase isoenzymes

In the 48 h following a single i.p. injection of 200 mg of thioacetimide/kg body wt there is a progressive rise in low- K m hexokinase activity and a concomitant decrease in high- K m glucokinase activity. Loss of glucokinase activity occurs as a consequence of its predominantly perivenous zonal distribution in normal liver since it is hepatocytes in this region of the acinus that are selectivity damage by thioacetamide. Increased low- K m activity is mainly present in inlammatory infiltrates which invade perivenous and mid-zone regions in response to tissue injury. Low- and high- K m hexokinase activities return to control levels 10 days after thioacetamide treatment when the infiltration zones disappear and necrotic perivenous hepatocytes are replaced by cells with normal morphology. Changes in low- and high- K m hexokinase activities induced by thioacetamide thus appear to primarily reflect alterations in cell population rather than changes in gene expression within existing hepatocytes.

Mechanisms of hypoglycemic activity of Aconitan A, a glycan from Aconitum carmichaeli roots

Aconitan A did not affect plasma insulin levels in normal, glucose-loaded and alloxan-induced hyperglycemic mice and gave no influence on insulin binding to isolated adipocytes. Aconitan A exerted no effect on the activities of hepatic hexokinase, glucokinase, glucose-6-phosphatase and glucose-6-phosphate dehydrogenase, whereas it significantly increased hepatic phosphofructokinase activity. Although the activity of hepatic glycogen synthetase showed a tendency to increase, the activity of liver phosphorylase and glycogen content were unchanged by aconitan A. Aconitan A did not change the total cholesterol and triglyceride contents of plasma and liver.

Hepatic enzyme activities and plasma insulin concentrations in diabetic herbivorous voles

The activities of the hepatic glycolytic enzymes glucokinase (GKase) and hexokinase (HKase) in herbivorous Microtus arvalis were very low and the hepatic fructose-1,6-diphosphatase (FDPase) activities were almost the same as those in C57BL/6J mice. Glycosuria was observed in over 50% of voles fed on a low fibre, high concentrate diet. Voles with a high incidence of glycosuria for over 6 weeks became insulin deficient. In these diabetic voles, the hepatic GKase, HKase and FDPase activities decreased considerably as a result of diminished insulin secretion and fatty degeneration of the hepatic cells. It was considered that M. arvalis would be a useful animal model in which to study disorders of glucose utilization in herbivora.

Physiological and metabolic changes associated with weaning in the tammar wallaby, Macropus eugenii.

The tammar wallaby (Macropus eugenii) is a small macropodid marsupial in which the major part of weaning occupies the period between 28 and 36 weeks of pouch life. Before weaning the diet of the tammar is high in carbohydrate and low in lipid/volatile fatty acid whereas the reverse applies after weaning. The adult tammar is a forestomach fermenter. The aim of this study was to elucidate some of the physiological and metabolic changes associated with this major change in the diet. Hepatic glycogen content increased gradually early in development to a maximum of 7% of liver weight at 28-30 weeks of pouch life. It then fell precipitously to less than 1% of liver weight at 36 weeks before recovering to the adult level of about 3% liver weight. Plasma glucose levels were maintained at about 10 mM until 36 weeks, after which they fell gradually to adult values of about 4 mM. Hepatic hexokinase activity increased several-fold between 18 and 30 weeks of pouch life, remained high until 42 weeks, and then fell to the adult level. The hepatic activities of fructose-bisphosphatase and particulate phosphoenolpyruvate carboxykinase (PEPCK) were unchanged during development but soluble hepatic PEPCK activity, which was low until 28 weeks of pouch life, increased 3-4 fold between 30 and 36 weeks and then fell slightly to the adult level. Hepatic pyruvate kinase increased in activity up to 28 weeks and then fell to about half peak values at 36 weeks and 20% of peak activity in the adult.(ABSTRACT TRUNCATED AT 250 WORDS)

The insulin-mimetic action of Mn 2+: Involvement of cyclic nucleotides and insulin in the regulation of hepatic hexokinase and glucokinase

Manganese causes a significant rise in hepatic glucokinase and hexokinase in 16-day-old suckling rats, and has an insulinomimetic effect in producing a precocious emergence of glucokinase (EC 2.7.1.2) and a rise in the low K m , kexokinases (EC 2.7.1.1) activities. These enzyme changes occur within 6 hr of manganese administration and there are accompanying increases in plasma insulin and hepatic cyclic GMP. That the effect of manganese is at a site other than, or in addition to, insulin secretion is suggested by the significant increases in glucokinase and hexokinase in 16-day-old streptozotocin-diabetic rats; in this group there is also an increase in hepatic cGMP similar in time scale to that of the normal-manganese-treated group. The effects of manganese and insulin were not additive. It is proposed that one site of action of manganese may be at the level of cyclic GMP systems. The results are also discussed in relation to the known action of manganese at the level of the protein phosphatases.

Purification of the hexokinases by affinity chromatography on sepharose-N-aminoacylglucosamine derivates. Design of affinity matrices from free solution kinetics

The purification is described of rat hepatic hexokinase type III and kidney hexokinase type I on a large scale by using a combination of conventional and affinity techniques similar to those previously used for the purification of rat hepatic glucokinase [Holroyde, Allen, Storer, Warsy, Chesher, Trayer, Cornish-Bowden & Walker (1976) Biochem. J. 153, 363-373] and muscle hexokinase type II [Holroyde & Trayer (1976) FEBS Lett. 62, 215-219]. The key to each purification was the use of a Sepharose-N-aminoacylglucosamine affinity matrix in which a high degree of specificity for a particular hexokinase isoenzyme could be introduced by either varying the length of the aminoacyl spacer and/or varying the ligand concentration coupled to the gel. This was predicted from a study of the free solution kinetic properties of the various N-aminoacylglucosamine derivatives used (N-aminopropionyl, N-aminobutyryl, N-aminohexanoyl and N-aminooctanoyl), synthesized as described by Holroyde, Chesher, Trayer & Walker [(1976) Biochem. J. 153, 351-361]. All derivatives were competitive inhibitors, with respect to glucose, of the hexokinase reaction, and there was a direct correlation between the Ki for a particular derivative and its ability to act as an affinity matrix when immobilized to CNBr-activated Sepharose 4B. Muscle hexokinase type II could be chromatographed on the Sepharose conjugates of all four N-aminoacylglucosamine derivatives, although the N-aminohexanoylglucosamine derivative proved best. This same derivative was readily able to bind hepatic glucokinase and hexokinase type III, but Sepharose-N-amino-octanoyl-glucosamine was better for these enzymes and was the only derivative capable of binding kidney hexokinase type I efficiently. Separate studies with yeast hexokinase showed that again only the Sepharose-N-amino-octanoylglucosamine was capable of acting as an efficient affinity matrix for this enzyme. Implications of these studies in our understanding of affinity-chromatography operation are discussed.