Endogenous Glucose Metabolism Research Articles

Characterization of glucose metabolism in high-growth performance Nile tilapia (Oreochromis niloticus)

Significant differences in growth performance have been observed in fish that have undergone the same culture cycle, even under identical conditions, including genetic background, water environment, and feeding strategy. These differences may adversely affect the harvesting and subsequent processing of commercial fish. We have previously demonstrated that the genes of glucose metabolism in high-growth performance tilapia (Oreochromis niloticus) showed significant upregulation at the transcriptome level. These findings suggested that the growth performance of tilapia may be closely related to their endogenous glucose metabolism capacity. To investigate the characteristics of glucose metabolism in high-growth performance tilapia, three full-sibling families were cultured under the same environmental and feeding conditions. The high-growth performance group (HG) and low-growth performance group (LG) were screened and compared at the biochemical and transcriptional levels during the postprandial period of 0 to 7 h. Based on biochemical analysis, HG had higher levels of intestinal lipase activity (0 to 1 h), serum triglyceride content (0 to 7 h), liver acetyl coenzyme A content (1 to 4 h), and liver glycogen content (0 to 1 h and 6 to 7 h) than LG. In contrast, HG had lower serum glucose content (0 h and 2 to 4 h), ATP content (4 to 7 h), and liver pyruvate content (3 to 4 h) than LG. There were no significant differences between HG and LG in liver ATP, intestinal α-amylase, and trypsin. We conducted a comprehensive analysis of gene expression within multiple metabolic pathways, namely the tricarboxylic acid cycle, glycolysis, pentose phosphate, glycogen metabolism, gluconeogenesis, and insulin signaling pathways, during three specific post-feeding periods: 0 to 1 h, 2–5 h, and 6 to 7 h, and revealed unique gene expression patterns related to glucose metabolic pathways in HG at different stages of post-feeding. We first revealed the endogenous glucose metabolism characteristics of high-growth performance tilapia. The findings will provide novel insights for further research on quality improvement related to growth performance in fish.

Biocatalytic production of 5-hydroxy-2-adamantanone by P450cam coupled with NADH regeneration

Abstract 5-Hydroxy-2-adamantanone is a versatile starting material for the synthesis of various adamantane derivatives. In this study, we investigated the biocatalytic production of 5-hydroxy-2-adamantanone using P450cam monooxygenase coupled with NADH regeneration. We constructed Escherichia coli cells that expressed P450cam and its redox partners, putidaredoxin and putidaredoxin reductase, and cells that co-expressed this P450cam multicomponent system with a glucose dehydrogenase (Gdh) to regenerate NADH using glucose. Two types of cells – wet cells that did not receive any treatment after washing with glycerol-containing buffer, and freeze-dried cells that were lyophilized after the washing – were prepared as whole-cell catalysts. When wet cells were reacted with 2-adamantanone, E. coli cells expressing only the P450cam multicomponent system efficiently produced 5-hydroxy-2-adamantanone in the presence of glucose. However, the co-expression of this P450cam system with Gdh did not further enhance the amount of this product. These results indicate that enough amounts of NADH for P450cam catalysis would be supplied by endogenous glucose metabolism in the E. coli host. In contrast, when freeze-dried cells were used, only the cells co-expressing the P450cam multicomponent system with Gdh efficiently catalyzed the oxidation in the presence of glucose. These results suggest that the exogenous Gdh compensated loss of NADH regeneration by the endogenous glucose metabolism that would be damaged by the lyophilization process. Furthermore, we attempted to produce 5-hydroxy-2-adamantanone with repeated additions of the substrate using wet cells expressing only the P450cam multicomponent system and freeze-dried cells co-expressing this P450cam system with Gdh. These whole-cell catalysts attained high-yield production; the wet cells and the freeze-dried cells produced 36 mM (5.9 g/l) and 21 mM (3.5 g/l) of 5-hydroxy-2-adamantanone, respectively.

Level of dietary protein intake affects glucose turnover in endurance-trained men

BackgroundTo examine the effects of higher-protein diets on endogenous glucose metabolism in healthy, physically active adults, glucose turnover was assessed in five endurance-trained men (age 21.3 ± 0.3 y, VO2peak 70.6 ± 0.1 mL kg-1 min-1) who consumed dietary protein intakes spanning the current dietary reference intakes.FindingsUsing a randomized, crossover design, volunteers consumed 4 week eucaloric diets providing either a low (0.8 g kg-1 d-1; LP), moderate (1.8 g kg-1 d-1; MP), or high (3.6 g kg-1 d-1; HP) level of dietary protein. Glucose turnover (Ra, glucose rate of appearance; and Rd glucose rate of disappearance) was assessed under fasted, resting conditions using primed, constant infusions of [6,6-2H2] glucose. Glucose Ra and Rd (mg kg-1 min-1) were higher for MP (2.8 ± 0.1 and 2.7 ± 0.1) compared to HP (2.4 ± 0.1 and 2.3 ± 0.2, P < 0.05) and LP (2.3 ± 0.1 and 2.2 ± 0.1, P < 0.01) diets. Glucose levels (mmol/L) were not different (P > 0.05) between LP (4.6 ± 0.1), MP (4.8 ± 0.1), and HP (4.7 ± 0.1) diets.ConclusionsLevel of protein consumption influenced resting glucose turnover in endurance athletes in a state of energy balance with a higher rate of turnover noted for a protein intake of 1.8 g kg-1 d-1. Findings suggest that consumption of protein in excess of the recommended dietary allowance but within the current acceptable macronutrient distribution range may contribute to the regulation of blood glucose when carbohydrate intake is reduced by serving as a gluconeogenic substrate in endurance-trained men.

Regulation of exogenous and endogenous glucose metabolism by insulin and acetoacetate in the isolated working rat heart. A three tracer study of glycolysis, glycogen metabolism, and glucose oxidation.

Myocardial glucose use is regulated by competing substrates and hormonal influences. However, the interactions of these effectors on the metabolism of exogenous glucose and glucose derived from endogenous glycogen are not completely understood. In order to determine changes in exogenous glucose uptake, glucose oxidation, and glycogen enrichment, hearts were perfused with glucose (5 mM) either alone, or glucose plus insulin (40 microU/ml), glucose plus acetoacetate (5 mM), or glucose plus insulin and acetoacetate, using a three tracer (3H, 14C, and 13C) technique. Insulin-stimulated glucose uptake and lactate production in the absence of acetoacetate, while acetoacetate inhibited the uptake of glucose and the oxidation of both exogenous glucose and endogenous carbohydrate. Depending on the metabolic conditions, the contribution of glycogen to carbohydrate metabolism varied from 20-60%. The addition of acetoacetate or insulin increased the incorporation of exogenous glucose into glycogen twofold, and the combination of the two had additive effects on the incorporation of glucose into glycogen. In contrast, the glycogen content was similar for the three groups. The increased incorporation of glucose in glycogen without a significant change in the glycogen content in hearts perfused with glucose, acetoacetate, and insulin suggests increased glycogen turnover. We conclude that insulin and acetoacetate regulate the incorporation of glucose into glycogen as well as the relative contributions of exogenous glucose and endogenous carbohydrate to myocardial energy metabolism by different mechanisms.

Plasma glucose turnover and oxidation during hemodialysis: nutritional effect of dialysis fluid

Mass transfer of glucose from dialysis fluid into patients is a source of energy and a form of nutrition during hemodialysis. The effect of glucose mass transfer on endogenous glucose metabolism and the overall nutritional importance of glucose transfer is not known. Rates of plasma glucose turnover and oxidation were determined by radioisotope-dilution techniques in patients with chronic renal failure (CRF) in the basal state, during hemodialysis, and during the infusion of glucose at a rate similar to the mass transfer rate (Mt: 6.6 +/- 0.7 mumol.min-1.kg-1). Rates of plasma glucose turnover (11.8 +/- 0.8 mumol.min-1.kg-1) and oxidation (4.0 +/- 0.4 mumol.min-1.kg-1) and contribution of glucose oxidation to the metabolic rate were similar to those of control subjects both in the basal state and during glucose infusion. During hemodialysis with acetate and glucose, the plasma glucose turnover rate was similar to that in the basal state, but the energy from glucose oxidation was less (P < or = 0.02) even though energy expenditure was increased by 21%. Immediate oxidation of plasma glucose and acetate accounted for 65% of the patients' energy expenditure. Energy (1172 kJ) from acetate Mt and glucose Mt surpassed the patients' energy requirements, offsetting the utilization of endogenous fuels, a sparing effect equivalent to 31 g fat or 70 g carbohydrate. Rates of plasma glucose turnover and oxidation during bicarbonate-glucose and glucose-free acetate hemodialysis were similar to that during acetate-glucose hemodialysis. However, without glucose or acetate in the bath fluid, a deficit as much as 669 kJ must be met by the oxidation of endogenous fuels. Addition of organic nutrients that supply energy to dialysis fluids may over time be a beneficial supplemental treatment for the malnutrition and body wasting commonly observed in CRF.

Insulin action and glucose metabolism in sheep fed on dried-grass or ground, maize-based diets.

The effect of an exogenous supply of glucose, provided by the digestion of maize starch in the small intestine, on endogenous glucose metabolism and insulin action was studied in sheep using the euglycaemic insulin clamp procedure. Insulin was infused intravenously at rates of 0.2, 0.5, 1.0 and 6.0 mU/min per kg live weight for four consecutive periods in each of four sheep fed on dried-grass and maize-based diets. Glucose was also infused intravenously at a variable rate, sufficient to maintain the plasma glucose concentration at basal levels. Whole-body rates of glucose metabolism were determined using a continuous infusion of [6-3H]glucose. From the resulting insulin dose-response curves, it was observed that, when the sheep were fed on the dried-grass diet, the responsiveness of glucose metabolism to insulin was less than that reported for non-ruminants. When fed the maize-based diet, the glucose metabolic clearance rates (MCR) observed during insulin infusions were significantly greater (P less than 0.05) than those observed for the dried-grass diet. However, after correcting for the non-insulin-mediated glucose disposal, differences between diets were not significant. The sensitivity of glucose utilization to insulin was not affected by diet. The plasma insulin concentrations causing half-maximal insulin-mediated glucose MCR were 103 (SE 21) and 85 (SE 11) mU/l for the dried-grass and maize-based diets respectively. The sensitivity of endogenous glucose production to insulin was also unaffected by diet. The plasma insulin concentrations resulting in the suppression of endogenous glucose production to half the basal level were 80 (SE 26) and 89 (SE 29) mU/l for the dried-grass and maize-based diets respectively. It is concluded that the observed increase in glucose utilization on the maize-based diet was due partly to a slight change in responsiveness to insulin and also partly to a change in the rate of non-insulin-mediated glucose disposal.

O.1 Glucose metabolism in the protein depleted rat: Basal glucose turnover and a comparison of the effect of glucose and lipid infusions

Many malnourished patients receive intravenous non-protein nutrition as either a glucose or lipid or a combination of both. However some studies have shown that malnutrition causes glucose intolerance. The precise role of fat as an energy source in malnutrition is unknown. The purpose of this study was to compare the effects of glucose and lipid infusion~ on glucose metabolism in malnourished rats. We used tracer methodology using 6 H glucose as it has been shown to be a highly accurate method for investigating glucose turnover compared with a glucose tolerance test. Animals (250g) were fed isocaloric diets of 14% (control) and 4% (malnourished) protein for 6 weeks. Studies were performed after a 48 hour fast, when we measured both basal glucose concentration and turnover and also how equicaloric exogenous glucose or long chain triglyceride infusions altered glucose kinetics. Malnourished rats lost body weight compared with the control rats over the 6 week diet (-1.8 + 7.9% v 38.5 + 10.0% Mean +sem p<0.001) and basal plasma glucose (5.8 ~ 0.5 v 6.9 + 0.2 umolTl p< 0.05) insulin (11.3 +1.3 v 36 +4.7 uU/ml p<0.002) concentrations were--lower. The tracer studies showed that the relative hypoglycaemia was due to decreased endogenous glucose production. Clearance of the exogenous glucose infusion however was equally effective in both control and malnourished animals (9.0 + 0.3 v 9.4 +0.7 ml/kg/min) as was suppression of endogenous glucose production (42.7 + 5.7% v 40~3 + 9.9%). Exogenous lipid did not alter plasma glucose concentration nor glucose--kinetics in either group. Insulin concentration increased in both groups after glucose infusion but percentage increases were not significantly different. Our studies show that protein depletion causes changes in endogenous glucose metabolism. However intravenous infusions of glucose are cleared quite normally from the blood and glucose kinetics are not altered by a lipid infusion. It is likely that glucose intolerance due to protein depletion is a myth.

TSH stimulation of 14C-amino acid incorporation into protein by isolated bovine thyroid cells.

The stimulatory action of TSH on 14C-leucine and 14C-tyrosine incorporation into protein by isolated bovine thyroid cells was investigated. When the cells were preincubated with actinomycin D so that RNA synthesis was severely inhibited, the TSH stimulation of protein synthesis was not greatly impaired. Hence, this action of TSH is not dependent on increased template RNA synthesis. Basal and TSH-stimulated levels of 14C-leucine incorporation could be depressed by omission of exogenous glucose. Furthermore, basal 14C-leucine incorporation was severely depressed and TSH stimulation was abolished when endogenous glucose metabolism was inhibited with 2-deoxyglucose. Therefore, it is concluded that the TSH effect on protein synthesis could be secondary to its stimulation of glucose metabolism. (Endocrinology 80: 1101, 1967)

Determination of rates of glucose oxidation in normal and diabetic dogs by a technique involving continuous injection of C14-glucose.

A procedure involving the continuous intravenous injection of C14-labeled glucose for measuring the rates of glucose oxidation and turnover in the dog is described. The total amount of labeled glucose administered during 6 hours need not exceed 0.1 mg, an amount quite negligible with respect to the size of the glucose pool in the dog and, consequently, too small to disturb the steady state of endogenous glucose metabolism. The advantage of this procedure lies in the fact that the calculations made are free of assumptions required in the single-injection method. As determined by the continuous-injection method, the normal dog oxidizes glucose at a rate of about 100 mg/kg/hr., and the diabetic dog (completely depancreatized) oxidizes glucose at a rate of about 50 mg/kg/hr. The injection of insulin in the diabetic dog restores the rates of glucose oxidation to near normal. A discussion is presented on the validity of the single-injection procedure for determination of rates of glucose oxidation in animals.