The effects of starvation and force-feeding on the metabolism of the Northern pike, Esox lucius L.

The effects of starvation and force-feeding on certain tissue and blood constituents were studied in the Northern pike, Esox lucius L. Starvation resulted in a reduction of liver and muscle glycogen and liver lipid. Blood glucose concentration and haematocrit were reduced, total plasma cholesterol levels were increased, while the levels of plasma free fatty acids (FFA), amio acid nitrogen and protein remained unaltered. No significant changes were observed in either muscle protein, muscle water or the response to amino acid loading during the starvation period.
The force-feeding of pike starved for 3 months resulted in liver lipid and muscle glycogen being increased to levels higher than those observed in freshly-captured fish. Liver glycogen, however, increased to values only slightly higher than those of starved animals. Furthermore, while force-feeding had little effect on plasma FFA or protein concentrations, blood glucose, plasma cholesterol and haematocrit returned to the levels found in freshlycaptured fish and those of amino acid nitrogen were higher.
The results indicate that pike are well adapted for periods of prolonged starvation and that hepatic and extra-hepatic lipid and glycogen stores serve for metabolic needs during food shortage, while body protein is conserved. The endocrine basis for these changes in the tissue and blood constituents is discussed.     

Intraportal autotransplantation of cryopreserved porcine islets of Langerhans

Mechanically prepared isolated islets of Langerhans were cryopreserved in liquid nitrogen for a period of 4 days. Intraportal autotransplantation studies were performed on two groups of six pigs rendered diabetic by total pancreatectomy (group 2) or by partial pancreatectomy combined with streptozotocin (group 4) and compared with two control groups (groups 1 and 3, respectively). The pigs were assessed for survival, weight gain, glycosuria, polyuria, systemic blood sugar and insulin, and, in selected pigs, intravenous glucose tolerance tests. Results showed that partial pancreatectomy with streptozotocin was the better tolerated experimental diabetes. Variable control of hyperglycemia was obtained over an experimental period of 3 months. Random blood glucose returned to normal in one of six pigs in the totally pancreatectomized group and three of six pigs in the partial pancreatectomy and streptozotocin group. Despite these normal circulating glucose levels, imperfect glucose homeostasis was achieved as shown by the response to glucose tolerance testing. These results report blood glucose control after cryopreserved islet autotransplants in diabetic pigs but further study is still necessary to achieve consistency.     

Haematological effects of stress on a teleost, Esox lucius L.

Stress produces a haemoconcentration, elevated blood lactate, increased glucose concentrations and alters the plasma electrolyte balance in two groups (brackish- and freshwater) of the northern pike, Esox leucius L., after one month's starvation. A method for dorsal aorta catheterization and a receptacle for cannulating fish is described.
The blood glucose level of the freshwater pike was twice that of the brackish-water group, and the plasma sodium and magnesium concentrations in the brackish-water pike were significantly higher. The haematocrit, haemoglobin and blood lactic acid concentrations were higher in freshwater pike. The plasma potassium and calcium concentrations in the two groups did not differ.
Haemoconcentration due to stress by handling for 1.5 min was shown by changes in haematocrit and haemoglobin values. The haemoglobin concentration returned to normal in freshwater pike after 4 h but in brackish-water pike after 12 h.
As a result of handling, the blood lactic acid level rose steeply and required 12 h to return to normal.
The blood glucose concentration rose to its maximum value within 1 h of handling and required two days to return to normal.
The plasma sodium level remained stable after handling, but the potassium level was erratic. In brackish-water, the potassium concentration of the pike remained high for 12 h after stress, but in the freshwater group, after a rise, the concentration fell to below the initial level within 4 h. The changes of the potassium concentrations in relation to sampling time are discussed. The changes in the divalent ion concentrations were marked and similar in the two groups; with an increase lasting 1–4 h and then a fall below the initial level, which was regained after two days.     

Interactive effects of naphthalene treatment and the onset of vitellogenesis on energy metabolism in liver and gonad, and plasma steroid hormones of rainbow trout Oncorhynchus mykiss

The purpose of the study was to assess in female fish the possible interaction between treatment with a polycyclic aromatic hydrocarbon (PAH) like naphthalene and the onset of vitellogenesis. In a first experiment, female rainbow trout (Oncorhynchus mykiss) at stages 2-3 (previtellogenesis) or 4 (early vitellogenesis) were intraperitoneally injected (2 microl g(-1)) with vegetable oil alone (control) or containing naphthalene (50 mg kg(-1)) to be sampled 3 h later. A second experiment was similarly designed but using fish intraperitoneally implanted (10 microl g(-1)) with slow-release coconut oil implants alone (control) or containing 50 mg naphthalene kg(-1) body mass that were sampled 3 days after injection. On each sampling time, plasma levels of cortisol and 17beta-estradiol, and several metabolic parameters in plasma, liver and gonad were assessed. In controls, early vitellogenic fish compared with previtellogenic fish displayed changes that in some cases are confirmatory of previous studies whereas in other cases provide new information in plasma (increased amino acid levels), liver (decreased capacity for exporting glucose and reduced amino acid levels) and gonad (decreased amino acid levels). Naphthalene treatment produced in previtellogenic fish decreased 17beta-estradiol levels in plasma, increased plasma glucose or decreased liver gluconeogenic capacity whereas no major effects were noticed on parameters involved in lipid, amino acid and lactate metabolism. Differential effects of naphthalene treatment were noticed in early vitellogenic fish such as decreased 17beta-estradiol and glucose levels in plasma, increased hexokinase and glucokinase and lack of changes in fructose 1,6-bisphosphatase activities in liver, and a lower decrease of amino acid levels in gonad. Those alterations produced by naphthalene treatment resulted in a decreased capacity for covering the energy demand of vitellogenesis in liver and gonad that could contribute to a delay and/or impairment of the onset of maturation.     

Secretin-stimulated insulin release in vivo in European eels, Anguilla anguilla L

Plasma insulin and glucose responses to a secretin-like factor, extracted from pike intestines, have been investigated in vivo in European eels, Anguilla anguilla L. Intra-arterial injection of pike secretin elicited a dose-related, significant increase of plasma insulin after 30 min at 100 and 250 μgkg^-1 body weight, but was without effect at 40μgkg^-1. Plasma glucose levels, however, remained unchanged over this dose range. These results suggest that hormonal factors of gastrointestinal origin may modify pancreatic endocrine function in teleost fish.     

Fish Oil and the Pan-PPAR Agonist Tetradecylthioacetic Acid Affect the Amino Acid and Carnitine Metabolism in Rats

Peroxisome proliferator-activated receptors (PPARs) are important in the regulation of lipid and glucose metabolism. Recent studies have shown that PPARα-activation by WY 14,643 regulates the metabolism of amino acids. We investigated the effect of PPAR activation on plasma amino acid levels using two PPARα activators with different ligand binding properties, tetradecylthioacetic acid (TTA) and fish oil, where the pan-PPAR agonist TTA is a more potent ligand than omega-3 polyunsaturated fatty acids. In addition, plasma L-carnitine esters were investigated to reflect cellular fatty acid catabolism. Male Wistar rats (Rattus norvegicus) were fed a high-fat (25% w/w) diet including TTA (0.375%, w/w), fish oil (10%, w/w) or a combination of both. The rats were fed for 50 weeks, and although TTA and fish oil had hypotriglyceridemic effects in these animals, only TTA lowered the body weight gain compared to high fat control animals. Distinct dietary effects of fish oil and TTA were observed on plasma amino acid composition. Administration of TTA led to increased plasma levels of the majority of amino acids, except arginine and lysine, which were reduced. Fish oil however, increased plasma levels of only a few amino acids, and the combination showed an intermediate or TTA-dominated effect. On the other hand, TTA and fish oil additively reduced plasma levels of the L-carnitine precursor γ-butyrobetaine, as well as the carnitine esters acetylcarnitine, propionylcarnitine, valeryl/isovalerylcarnitine, and octanoylcarnitine. These data suggest that while both fish oil and TTA affect lipid metabolism, strong PPARα activation is required to obtain effects on amino acid plasma levels. TTA and fish oil may influence amino acid metabolism through different metabolic mechanisms.     

The effects of insulin on plasma amino acid levels in the Northern pike, Esox lucius L

Cod and bovine insulin (2 i.u. kg⁻¹) were injected intra-arterially into cannulated Northern pike, Esox lucius L. and the levels of 13 plasma amino acids analysed by gas-liquid chroma-tography after 9 and 48 h. Both insulins caused an equally significant reduction in the level of each amino acid after 9 h which was followed by a recovery to near-control levels after 48 h. The data support the hypothesis that insulin plays a major role in the regulation of protein metabolism in this species.     

An amino acid mixture improves glucose tolerance and lowers insulin resistance in the obese Zucker rat

The purpose of this investigation was to test an amino acid mixture on glucose tolerance in obese Zucker rats [experiment (Exp)-1] and determine whether differences in blood glucose were associated with alterations in muscle glucose uptake [experiment (Exp)-2]. Exp-1 rats were gavaged with either carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1), carbohydrate plus amino acid mixture with increased leucine concentration (OB-AA-2) or water (OB-PLA). The glucose response in OB-AA-1 and OB-AA-2 were similar, and both were lower compared to OB-CHO. This effect of the amino acid mixtures did not appear to be solely attributable to an increase in plasma insulin. Rats in Exp-2 were gavaged with carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1) or water (OB-PLA). Lean Zuckers were gavaged with carbohydrate (LN-CHO). Fifteen minutes after gavage, a radiolabeled glucose analog was infused through a catheter previously implanted in the right jugular vein. Blood glucose was significantly lower in OB-AA-1 compared to OB-CHO while the insulin responses were similar. Glucose uptake was greater in OB-AA-1 compared with OB-CHO, and similar to that in LN-CHO in red gastrocnemius muscle (5.15 ± 0.29, 3.8 ± 0.27, 5.18 ± 0.34 µmol/100 g/min, respectively). Western blot analysis showed that Akt substrate of 160 kDa (AS160) phosphorylation was enhanced for OB-AA-1 and LN-CHO compared to OB-CHO. These findings suggest that an amino acid mixture improves glucose tolerance in an insulin resistant model and that these improvements are associated with an increase in skeletal muscle glucose uptake possibly due to improved intracellular signaling.     

Taurine attenuates hypertension and improves insulin sensitivity in the fructose-fed rat, an animal model of insulin resistance

Fructose feeding induces moderate increases in blood pressure levels in normal rats, which is associated with hyperinsulinemia, insulin resistance, and impaired glucose tolerance. Increased vascular resistance, sodium retention, and sympathetic overactivity have been proposed to contribute to the blood pressure elevation in this model. Taurine, a sulphur-containing amino acid, has been reported to have antihypertensive and sympatholytic actions. In the present study, the effects of taurine on blood pressure, plasma levels of glucose and insulin, glucose tolerance, and renal function were studied in fructose-fed rats. Fructose-fed rats had higher blood pressure and elevated plasma levels of insulin and glucose. The plasma glucose levels were higher in fructose-fed rats than in controls at 15, 30, and 60 min after the oral glucose load. Treatment with 2% taurine in drinking water prevented the blood pressure elevation and attenuated the hyperinsulinemia in fructose-fed rats. The exaggerated glucose levels in response to the oral glucose load was also prevented by taurine administration. Thus, taurine supplementation could be beneficial in circumventing metabolic alterations in insulin resistance.     

Effect of fasting, glucose, amino acids and food intake on in vivo insulin release in the chicken

Insulin release was studied in vivo in the chicken using the radioimmunoassay previously described (Simon, Freychet and Rosselin 1974). An orally administered glucose load (2 g/kg b.w.) stimulated insulin release and was rapidly metabolized. A prolonged fasting period (65 hr) increased both initial plasma glucose and initial plasma insulin levels and highly impaired the glucose tolerance. A fasting-impaired insulin release and/or a fasting tissue "insulin resistance" accounted for this fasting-impaired glucose tolerance. An orally administered amino acid mixture (1 g/kg b.w.) stimulated insulin release to a very low extent. The effect was however sufficient to decrease the plasma glucose level. In combination with glucose, the oral amino acid load potentiated the effect of a dose of glucose on insulin release and highly improved the glucose tolerance. This synergism was still observed with the intake of a mixed and balanced diet. Therefore, except for some characteristics observed in the chicken which are discussed, the insulin regulation and the pancreatic beta-cell function are qualitatively similar in the chicken and in mammals.     

Enhanced β-adrenergic receptors in the brain and pancreas during pancreatic regeneration in weanling rats

Adrenergic stimulation has an important role in the pancreatic β-cell proliferation and insulin secretion. In the present study, we have investigated how sympathetic system regulates the pancreatic regeneration by analyzing Epinephrine (EPI), Norepinephrine (NE) and β-adrenergic receptor changes in the brain as well as in the pancreas. EPI and NE showed a significant decrease in the brain regions, pancreas and plasma at 72 hrs after partial pancreatectomy. We observed an increase in the circulating insulin levels at 72 hrs. Scatchard analysis using [³H] propranolol showed a significant increase in the number of both the low affinity and high affinity β-adrenergic receptors in cerebral cortex and hypothalamus of partially pancreatectomised rats during peak DNA synthesis. The affinity of the receptors decreased significantly in the low and high affinity receptors of cerebral cortex and the high affinity hypothalamic receptors. In the brain stem, low affinity receptors were increased significantly during regeneration whereas there was no change in the high affinity receptors. The pancreatic β-adrenergic receptors were also up regulated at 72 hrs after partial pancreatectomy. In vitro studies showed that β-adrenergic receptors are positive regulators of islet cell proliferation and insulin secretion. Thus our results suggest that the β-adrenergic receptors are functionally enhanced during pancreatic regeneration, which in turn increases pancreatic β-cell proliferation and insulin secretion in weanling rats.     

Glucagon secretion during the development of insulin-secreting tumors induced by streptozotocin and nicotinamide.

Serial oral glucose tolerance tests in rats treated with streptozotocin and nicotinamide showed that blood glucose levels after glucose loading were suppressed significantly 7 months after treatment as compared to those of earlier stages. Post-glucose plasma insulin levels were significantly elevated at the 9th to 12th month and concomitantly fasting plasma glucagon levels rose significantly. At that time pancreatic islet cell tumors were demonstrated in all of the rats in this experiment. Post-glucose plasma glucagon levels, however, did not show remarkable changes throughout the observation. In spite of hyperinsulinemia, post-glucose plasma glucagon levels of tumor-bearing rats were significantly lower than those of body weight adjusted controls. It is inferred from the study that secretory activity of pancreatic A-cells of tumor-bearing rats is restrained by excess insulin released from islet cell tumors.     

Decreased 5-HT2C receptor binding in the cerebral cortex and brain stem during pancreatic regeneration in rats

The purpose of this study was to investigate the role of central 5-HT_2C receptor binding in rat model of pancreatic regeneration using 60–70% pancreatectomy. The 5-HT and 5-HT_2C receptor kinetics were studied in cerebral cortex and brain stem of sham operated, 72 h pancreatectomised and 7 days pancreatectomised rats. Scatchard analysis with [³H] mesulergine in cerebral cortex showed a significant decrease (p < 0.05) in maximal binding (B_max) without any change in K_d in 72 h pancreatectomised rats compared with sham. The decreased B_max reversed to sham level by 7 days after pancreatectomy. In brain stem, Scatchard analysis showed a significant decrease (p < 0.01) in B_max with a significant increase (p < 0.01) in K_d. Competition analysis in brain stem showed a shift in affinity towards a low affinity. These parameters were reversed to sham level by 7 days after pancreatectomy. Thus the results suggest that 5-HT through the 5-HT_2C receptor in the brain has a functional regulatory role in the pancreatic regeneration.     

Plasma Glucagon Levels Suppressed by a Glucose Load in a Man with Incidental Pancreatic Glucagonoma

ObjectiveTo describe a patient with a histologically proven pancreatic glucagonoma, noted incidentally during a follow-up visit for high aminotransferase levels, and to evaluate its autonomy with a standard 75-g oral glucose tolerance test.MethodsWe present the results of a 2-hour oral glucose tolerance test, with plasma glucagon and blood glucose levels measured every 30 minutes after an oral glucose load. In addition, we provide a brief review of the literature on the diagnosis and management of glucagonomas and the importance of long-term surveillance.ResultsIn our patient, who had a 1-year history of impaired fasting glucose, plasma glucagon levels were persistently suppressed to within the normal range after oral glucose challenge. Octreotide scintigraphy revealed abnormal uptake in the pancreatic tail, and a 2.8-cm mass was removed at laparoscopic distal pancreatectomy. Immunohistochemical staining of the tumor tissue showed intense reactivity for glucagon. Plasma glucagon levels were reduced to < 50 pg/mL postoperatively, and scintigraphic study at 4-month follow-up showed no residual uptake at the previous tumor site or elsewhere.ConclusionGlucagon-secreting pancreatic tumors are extremely rare. A substantially elevated plasma level of glucagon is usually seen in patients with metastatic tumors. In the early stage of a glucagonoma, however, the plasma glucagon level may be only modestly elevated and may still be susceptible to normal negative feedback inhibition. We demonstrated plasma glucagon complete suppressibility after oral glucose challenge in a patient with a glucagonoma, the first such report in the literature. (Endocr Pract. 2007;13:780-784)     

Dietary supplementation of essential fatty acids in larval pikeperch (Sander lucioperca); short and long term effects on stress tolerance and metabolic physiology

The present study examined the effects of feeding pike perch larvae Artemia, enriched with either docosahexanoic acid (DHA), arachidonic acid (ARA), oleic acid (OA), olive oil (OO) or a commercial enrichment DHA Selco (DS) on tissue lipid deposition, stress tolerance, growth and development, and metabolic rate. There was higher tissue retention of ARA than DHA at comparable inclusion levels. No differences were observed between diets on the percentage contribution of ARA or DHA to the fatty acid profile of tissues (head and trunk). Total fatty acid content (mgg(-1)) was significantly higher in the head, reflecting its high content of neural tissue. Observations on larval erratic behaviour and mortality following exposure to salinity stress suggested that high inclusions levels of DHA had an alleviating effect, while ARA did not. Particularly larval groups reared for 16 days on diets enriched with OO and OA had mortality rates approaching 100% within two hours. Interestingly, this tendency, although not as pronounced, was also apparent in juvenile fish after 120 days of rearing on a common diet. Standard metabolic rate in larvae on an OO enriched diet was significantly elevated, but otherwise no groups had significant changes to their respiratory physiology. In addition to increased stress challenge sensitivity, early feeding with OA had long term impact on pike perch neural development indicated by a smaller brain size in juvenile fish. In conclusion, lack of DHA in the diet of pikeperch larvae suggests that this long chain polyunsaturated fatty acid is involved in processes that increase stress tolerance and that lack of dietary DHA in early larval stage caused increased stress sensitivity and long-term impaired neural development, while it does not appear to affect metabolic rate at rest.     

Decreased GABA<Subscript>A</Subscript> Receptor Function in the Brain Stem during Pancreatic Regeneration in Rats

Gamma amino butyric acid is a major inhibitory neurotransmitter in the central nervous system. In the present study we have investigated the alteration of GABA receptors in the brain stem of rats during pancreatic regeneration. Three groups of rats were used for the study: sham operated, 72 h and 7 days partially pancreatectomised. GABA was quantified by [³H]GABA receptor displacement method. GABA receptor kinetic parameters were studied by using the binding of [³H]GABA as ligand to the Triton X-100 treated membranes and displacement with unlabelled GABA. GABA_A receptor activity was studied by using the [³H]bicuculline and displacement with unlabelled bicuculline. GABA content significantly decreased (P < 0.001) in the brain stem during the regeneration of pancreas. The high affinity GABA receptor binding showed a significant decrease in B _max (P < 0.01) and K _d (P < 0.05) in 72 h and 7 days after partial pancreatectomy. [³H]bicuculline binding showed a significant decrease in B _max and K _d (P < 0.001) in 72 h pancreatectomised rats when compared with sham where as B _max and K _d reversed to near sham after 7 days of pancreatectomy. The results suggest that GABA through GABA receptors in brain stem has a regulatory role during active regeneration of pancreas which will have immense clinical significance in the treatment of diabetes.     

Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis

Glucagon plays an important role in glucose homeostasis and amino acid metabolism. It regulates plasma amino acid levels which in turn modulate glucagon secretion from the pancreatic α-cell, thereby establishing a liver–α-cell axis described recently. We reported previously that the knock-in mice bearing homozygous V369M substitution (equivalent to a naturally occurring mutation V368M in the human glucagon receptor, GCGR) led to hypoglycemia with improved glucose tolerance. They also exhibited hyperglucagonemia, pancreas enlargement and α-cell hyperplasia. Here, we investigated the effect of V369M/V368M mutation on glucagon-mediated amino acid metabolism. It was found that Gcgr^V369M+/+ mice displayed increased plasma amino acid levels in general, but significant accumulation of the ketogenic/glucogenic amino acids was observed in animals fed with a high-fat diet (HFD), resulting in deleterious metabolic consequence characteristic of α-cell proliferation and hyperglucagonemia.     

The effect of hypophysectomy and hypophysis-transplantation on the secretion of gut glucagon immunoreactivity and gut glucagon-like immunoreactivity in depancreatized dogs

The role of hypophysis in the regulation mechanism of the secretion of gut glucagon immunoreactivity (gut GI) that was measured using C-terminal specific glucagon antiserum after pancreatectomy, and gut glucagon-like immunoreactivity (gut GLI) that was obtained by subtracting GI from total glucagon-like immunoreactivity (total GLI) which was measured using non-specific glucagon antiserum, was investigated in depancreatized dogs. Plasma glucose, gut GI and gut GLI levels were found to increase in totally depancreatized dogs. The former two showed a significant decrease after hypophysectomy, and were reversed by the hypophysis-transplantation, while gut GLI was not affected either by hypophysectomy or hypophysis-transplantation. Intramuscular injections of human growth hormone (HGH) or adrenocorticotropic hormone-Z (ACTH-Z) to depancreatized-hypophysectomized dogs had no effect on plasma glucose level or gut GI. It is concluded that hypophysis may promote the secretion of gut GI after pancreatectomy, but not of gut GLI. Gut GI seems to regulate plasma glucose level after pancreatectomy. However, the precise regulation mechanism of gut GI by the hypophysial hormone after pancreatectomy is not clarified yet.     

Daily changes in parameters of energy metabolism in brain of rainbow trout: dependence on feeding

We assessed the daily patterns of parameters involved in energy metabolism in plasma and brain of rainbow trout. Where daily rhythms were found, we analyzed the potential influence of feeding. Immature rainbow trout were randomly distributed in 3 groups: fish fed for 7 days, fish fasted for 7 days, and fish fasted for 7 days and refed for 4 days. On sampling day, fish of fed and refed groups were fed at 11.00 h, and all fish were sampled from each treatment group using the following time schedule: 14.00, 18.00, 21.00, 00.00, 04.00, 07.00, 10.00 and 14.00 h. The results obtained from metabolic parameters assessed in plasma and brain can be grouped into three different categories, such as (i) those displaying no 24 h changes in fed fish such as plasma lactate, protein or acetoacetate levels, as well as brain amino acid and protein levels, and lowKm(glucose) hexokinase, and aspartate aminotransferase activities, (ii) those displaying 24 h changes that were apparently dependent on feeding since they disappeared in fasted fish such as the case of plasma cortisol, glucose and triglyceride levels, as well as brain glycogen, glucose, and lactate levels, and pyruvate kinase and hexokinase IV activities, and (iii) those parameters displaying 24 h changes apparently not dependent on feeding such as plasma amino acids, brain acetoacetate levels as well as several enzyme activities measured in brain such as glucose 6-phosphate dehydrogenase, alpha-glycerophosphate dehydrogenase, glutamate dehydrogenase, and lactate dehydrogenase-oxidase. In general, 24 h changes dependent on feeding indicate an increased use of glucose in brain several hours post-feeding whereas those changes not dependent on feeding were characterized by reduced levels/activity at the night period suggesting a metabolic depression in brain during darkness.     

Metabolomic analysis of a human oral glucose tolerance test reveals fatty acids as reliable indicators of regulated metabolism

Gas chromatography/mass spectrometry-based metabolomics was applied to investigate dynamic changes in the plasma metabolome upon an oral glucose tolerance test (OGTT). The OGTT is a frequently used diagnostic test of glucose homeostasis and diabetes. Diabetes is diagnosed either when glucose levels ≥7.0 mM in the fasting state or ≥11.0 mM at 2 h after oral glucose intake. The accuracy of the OGTT would, however, most likely improve if additional variables could be identified. In the present study, plasma samples were drawn every 15 min for 2 h after an oral glucose load of 75 g preceded by an overnight fast in healthy individuals. Blood plasma levels of more than 200 putative metabolites were measured. Multivariate modelling was used to distinguish metabolic regulation due to the glucose challenge from that of other variability. Two data scaling methods were applied, yielding similar results when evaluated by appropriate diagnostic tools. Fatty acid levels were found to be strongly decreased during the OGTT. Also, the levels of amino acids were shown to decrease. However, technical and uninduced biological variations were found to affect the amino acid levels to a greater extent than the fatty acid levels, making the fatty acids more reliable as indicators of metabolic regulation. Levels of several metabolites correlated with the quadratic glucose profile and two were found having an inverse correlation. Raw data plots of all identified significantly altered metabolites confirmed the excellent performance of the multivariate models. Using this approach, a better understanding of the metabolic response to an OGTT can be achieved, paving the way for inclusion of other variables describing appropriate metabolic control.