Interaction of dietary fibre, carbohydrate metabolism and diabetes in the rat

It is currently accepted that the most appropriate diet in the treatment of non-insulin-dependent diabetes mellitus "e;NIDDM"e; is high in carbohydrates, high in fibre and low in fat. Dietary fibre reduces the rate of carbohydrate absorption, which may have a beneficial effect on insulin action. Furthermore, high fibre diets also increase the amount of carbohydrates which are not absorbed from the small intestine. These malabsorbed carbohydrates are fermented by the bacterial population in the large intestine, producing short chain fatty acids "e;SCFA"e;, including propionate, which has been shown to alter liver carbohydrate metabolism. This thesis investigated the actions of slowed carbohydrate absorption and carbohydrate malabsorption in streptozotocin-induced "e;STZ"e; diabetic rats. High carbohydrate diet supplemented with guar gum, a soluble dietary fibre, fed to STZ diabetic rats improved insulin sensitivity. investigation of the alterations in the stomach and small intestine demonstrated that guar increased the viscosity of the meal in the intestine. The action of increased fermentation, producing more propionate, was investigated by supplementing propionate into the diets of STZ diabetic rats or when perfused into isolated rat livers. No changes in insulin action or liver glucose metabolism were measured. in addition, it was shown that guar gum reduces food intake in STZ diabetic rats. Mild reductions in food intake in STZ diabetic rats were shown to increase insulin action. In summary, STZ diabetic rats fed high carbohydrate, high fibre diets reductions in food consumption and slowed carbohydrate absorption are important factors which may lower blood glucose concentrations and increase insulin action. increased SCFA production is unlikely to contribute significantly to the improvements in insulin action.

Adrenergic regulation of carbohydrate metabolism during exercise

1. This series of studies was undertaken to examine the adrenergic regulation of carbohydrate metabolism during exercise. Recreationally active males were tested during moderate to intense exercise on a stationary cycle ergometer. Venous and arterial plasma obtained from indwelling catheters was analysed for hormonal and metabolite responses, and hepatic glucose production and glucose uptake were measured using the tracer-dilution method with stable isotopes. Muscle samples were obtained by the needle biopsy technique to examine muscle glycogen utilisation and the flux of related muscle metabolites using enzymatic, fluorometric and radioisotopic techniques. 2. During moderate exercise adrenaline infusion induced a marked hyperglycemia and this was due to reduced glucose uptake rather than enhanced hepatic glucose production. The reduction in glucose uptake was most likely mediated by a decrease in glucose phosphorylation, as indicated by the accumulation of glucose 6-phosphate with adrenaline infusion. 3. The hyperglycemic response to intense exercise was prevented by the administration of α- and β-adrenergic antagonists. Adrenergic blockade was without effect on hepatic glucose production whereas glucose uptake was enhanced when compared with control subjects. These data support the notion that adrenergic mechanisms are more important in restraining glucose uptake than enhancing hepatic glucose production during intense exercise. Other glucoregulatory factors are responsible for the increase in glucose production during intense exercise. 4. Elevated plasma adrenaline levels during moderate exercise in untrained men increases skeletal muscle glycogen breakdown and PDH activation which results

Body build : its influence on anthropometric measurements, fat distribution, body composition and carbohydrate metabolism

Examines the interrelationships between body build and body composition and carbohydrate and lipid metabolism in healthy young men and women. Results indicate that in women a low relative sitting height may be an early marker of susceptibility to abdominal obesity and its consequences, non insulin dependent diabetes and coronary heart disease.

Skeletal muscle GLUT-4 gene and protein regulation

Twenty two, young, healthy individuals participated in three studies aiming to assess the effect of various types of physical activity - acute exercise of moderate intensity and duration, varying intensity, short-term training - on skeletal muscle GLUT-4 gene and protein expression as well as on a range of genes encoding the proteins involved in carbohydrate metabolism in skeletal muscle.

Metabolite profiling reveals distinct changes in carbon and nitrogen metabolism in phosphate-deficient barley plants (Hordeum vulgare L.)

Plants modify metabolic processes for adaptation to low phosphate (P) conditions. Whilst transcriptomic analyses show that P deficiency changes hundreds of genes related to various metabolic processes, there is limited information available for global metabolite changes of P-deficient plants, especially for cereals. As changes in metabolites are the ultimate ‘readout’ of changes in gene expression, we profiled polar metabolites from both shoots and roots of P-deficient barley (Hordeum vulgare) using gas chromatography–mass spectrometry (GC-MS). The results showed that mildly P-deficient plants accumulated di- and trisaccharides (sucrose, maltose, raffinose and 6-kestose), especially in shoots. Severe P deficiency increased the levels of metabolites related to ammonium metabolism in addition to di- and trisaccharides, but reduced the levels of phosphorylated intermediates (glucose-6-P, fructose-6-P, inositol-1-P and glycerol-3-P) and organic acids (α-ketoglutarate, succinate, fumarate and malate). The results revealed that P-deficient plants modify carbohydrate metabolism initially to reduce P consumption, and salvage P from small P-containing metabolites when P deficiency is severe, which consequently reduced levels of organic acids in the tricarboxylic acid (TCA) cycle. The extent of the effect of severe P deficiency on ammonium metabolism was also revealed by liquid chromatography–mass spectrometry (LC-MS) quantitative analysis of free amino acids. A sharp increase in the concentrations of glutamine and asparagine was observed in both shoots and roots of severely P-deficient plants. Based on these data, a strategy for improving the ability of cereals to adapt to low P environments is proposed that involves alteration in partitioning of carbohydrates into organic acids and amino acids to enable more efficient utilization of carbon in P-deficient plants.

Pre-exercise nutritional strategies: effects on metabolism and performance

The goals of pre-exercise nutritional strategies are to optimise the availability of carbohydrate (CHO) and fluid. Ingestion of CHO 3-4 hr prior to exercise can increase liver and muscle glycogen stores and has been associated with enhanced endurance exercise performance. The metabolic effects of CHO ingestion persist for at least 6 hr. Although an increase in plasma insulin following CHO ingestion in the hour prior to exercise inhibits lipolysis and liver glucose output, and can lead to transient hypoglycemia during subsequent exercise, there is no convincing evidence that this is always associated with impaired exercise performance. Having said that, individual experience should inform individual practice. Interventions to increase plasma FFA availability prior to exercise have been shown to reduce CHO utilisation during exercise, but do not appear to have major ergogenic benefits. It is more difficult to hyperhydrate prior to exercise and although there has been interest in glycerol ingestion, to date research results have been equivocal. At the very least, athletes should ensure euhydration prior to exercise.

Effect of prior exercise on glucose metabolism in trained men.

Several studies have demonstrated that oral glucose tolerance is impaired in the immediate postexercise period. A double-tracer technique was used to examine glucose kinetics during a 2-h oral glucose (75 g) tolerance test (OGTT) 30 min after exercise (Ex, 55 min at 71 ± 2% of peak O₂ uptake) and 24 h after exercise (Rest) in endurance-trained men. The area under the plasma glucose curve was 71% greater in Ex than in Rest (P = 0.01). The higher glucose response occurred even though whole body rate of glucose disappearance was 24% higher after exercise (P = 0.04, main effect). Whole body rate of glucose appearance was 25% higher after exercise (P = 0.03, main effect). There were no differences in total (2 h) endogenous glucose appearance (R_aE) or the magnitude of suppression of R_aE, although R_aE was higher from 15 to 30 min during the OGTT in Ex. However, the cumulative appearance of oral glucose was 30% higher in Ex (P = 0.03, main effect). There were no differences in glucose clearance rate or plasma insulin responses between the two conditions. These results suggest that adaptations in splanchnic tissues by prior exercise facilitate greater glucose output from the splanchnic region after glucose ingestion, resulting in a greater glycemic response and, consequently, a greater rate of whole body glucose uptake.

Carbohydrate metabolism during exercise in females : effect of reduced fat availability

This study examined the effect of reduced plasma free fatty acid (FFA) availability on carbohydrate metabolism during exercise. Six untrained women cycled for 60 minutes at approximately 58% of maximum oxygen uptake after ingestion of a placebo (CON) or nicotinic acid (NA), 30 minutes before exercise (7.4 ± 0.5 mg·kg⁻¹ body weight), and at 0 minutes (3.7 ± 0.3 mg·kg⁻¹) and 30 minutes (3.7 ± 0.3 mg·kg⁻¹) of exercise. Glucose kinetics were measured using a primed, continuous infusion of [6,6-²H] glucose. Plasma FFA (CON, 0.86 ± 0.12; NA, 0.21 ± 0.11 mmol·L⁻¹ at 60 minutes, P < .05) and glycerol (CON, 0.34 ± 0.05; NA, 0.10 ± 0.04 mmol·L⁻¹ at 60 minutes, P < .05) were suppressed throughout exercise. Mean respiratory exchange ratio (RER) during exercise was higher (P < .05) in NA (0.89 ± 0.02) than CON (0.83 ± 0.02). Plasma glucose and glucose production were similar between trials. Total glucose uptake during exercise was greater (P < .05) in NA (1,876 ± 161 μmol·kg⁻¹) than in CON (1,525 ± 107 μmol·kg⁻¹). Total fat oxidation was reduced (P < .05) by approximately 32% during exercise in NA. Total carbohydrate oxidized was approximately 42% greater (P < .05) in NA (412 ± 40 mmol) than CON (290 ± 37 mmol), of which, approximately 16% (20 ± 10 mmol) could be attributed to glucose. Plasma insulin and glucagon were similar between trials. Catecholamines were higher (P < .05) during exercise in NA. In summary, during prolonged moderate exercise in untrained women, reduced FFA availability results in a compensatory increase in carbohydrate oxidation, which appears to be due predominantly to an increase in glycogen utilization, although there was a small, but significant, increase in whole body glucose uptake.

Exercise training increases lipid metabolism gene expression in human skeletal muscle

The effects of a single bout of exercise and exercise training on the expression of genes necessary for the transport and beta -oxidation of fatty acids (FA), together with the gene expression of transcription factors implicated in the regulation of FA homeostasis were investigated. Seven human subjects (3 male, 4 female, 28.9 ± 3.1 yr of age, range 20-42 yr, body mass index 22.6 kg/m², range 17-26 kg/m²) underwent a 9-day exercise training program of 60 min cycling per day at 63% peak oxygen uptake (V_{O2 peak}; 104 ± 14 W). On days 1 and 9 of the program, muscle biopsies were sampled from the vastus lateralis muscle at rest, at the completion of exercise, and again 3 h postexercise. Gene expression of key components of FA transport [FA translocase (FAT/CD36), plasma membrane-associated FA-binding protein], beta -oxidation [carntine palmitoyltransferase(CPT) I, beta -hydroxyacyl-CoA dehydrogenase] and transcriptional control [peroxisome proliferator-activated receptor (PPAR)alpha , PPARgamma , PPARgamma coactivator 1, sterol regulatory element-binding protein-1c] were unaltered by exercise when measured at the completion and at 3 h postexercise. Training increased total lipid oxidation by 24% (P < 0.05) for the 1-h cycling bout. This increased capacity for lipid oxidation was accompanied by an increased expression of FAT/CD36 and CPT I mRNA. Similarly, FAT/CD36 protein abundance was also upregulated by exercise training. We conclude that enhanced fat oxidation after exercise training is most closely associated with the genes involved in regulating FA uptake across the plasma membrane (FAT/CD36) and across the mitochondrial membrane (CPT I).

Elevation in tanis expression alters glucose metabolism and insulin sensitivity in H4IIE cells

Increased hepatic glucose output and decreased glucose utilization are implicated in the development of type 2 diabetes. We previously reported that the expression of a novel gene, Tanis, was upregulated in the liver during fasting in the obese/diabetic animal model Psammomys obesus. Here, we have further studied the protein and its function. Cell fractionation indicated that Tanis was localized in the plasma membrane and microsomes but not in the nucleus, mitochondria, or soluble protein fraction. Consistent with previous gene expression data, hepatic Tanis protein levels increased more significantly in diabetic P. obesus than in nondiabetic controls after fasting. We used a recombinant adenovirus to increase Tanis expression in hepatoma H4IIE cells and investigated its role in metabolism. Tanis overexpression reduced glucose uptake, basal and insulin-stimulated glycogen synthesis, and glycogen content and attenuated the suppression of PEPCK gene expression by insulin, but it did not affect insulin-stimulated insulin receptor phosphorylation or triglyceride synthesis. These results suggest that Tanis may be involved in the regulation of glucose metabolism, and increased expression of Tanis could contribute to insulin resistance in the liver.

A short-term, high-fat diet up-regulates lipid metabolism and gene expression in human skeletal muscle

Background: Dietary fatty acids may be important in regulating gene expression. However, little is known about the effect of changes in dietary fatty acids on gene regulation in human skeletal muscle.
Objective: The objective was to determine the effect of altered dietary fat intake on the expression of genes encoding proteins necessary for fatty acid transport and &szlig;-oxidation in skeletal muscle.
Design: Fourteen well-trained male cyclists and triathletes with a mean (&plusmn; SE) age of 26.9 &plusmn; 1.7 y, weight of 73.7 &plusmn; 1.7 kg, and peak oxygen uptake of 67.0 &plusmn; 1.3 mL &dot; kg-1 &dot; min-1 consumed either a high-fat diet (HFat: > 65% of energy as lipids) or an isoenergetic high-carbohydrate diet (HCho: 70–75% of energy as carbohydrate) for 5 d in a crossover design. On day 1 (baseline) and again after 5 d of dietary intervention, resting muscle and blood samples were taken. Muscle samples were analyzed for gene expression [fatty acid translocase (FAT/CD36), plasma membrane fatty acid binding protein (FABPpm), carnitine palmitoyltransferase I (CPT I), &szlig;-hydroxyacyl-CoA dehydrogenase (&szlig;-HAD), and uncoupling protein 3 (UCP3)] and concentrations of the proteins FAT/CD36 and FABPpm.
Results: The gene expression of FAT/CD36 and &szlig; -HAD and the gene abundance of FAT/CD36 were greater after the HFat than after the HCho diet (P < 0.05). Messenger RNA expression of FABPpm, CPT I, and UCP-3 did not change significantly with either diet.
Conclusions: A rapid and marked capacity for changes in dietary fatty acid availability to modulate the expression of mRNA-encoding proteins is necessary for fatty acid transport and oxidative metabolism. This finding is evidence of nutrient-gene interactions in human skeletal muscle.