Increased Plasma Glucose Concentrations Research Articles

ARSENIC DOSE AND ITS RELATION TO CARDIOVASCULAR RISK AMONG RESIDENTS IN MIDDLE TAIWAN

ISEE-34 Introduction / Aim: Arsenic has been found to be abundant in general, and much attention has been paid to the southwestern Pacific region. Blackfoot disease was found to be endemic in the southwestern coast of Taiwan, due to the ingestion of artesian well water with high arsenic concentrations. Even today, researchers still observe high rates of cancers and various vascular diseases in this area. However, much less information is known for the general population in Taiwan. Methods: In order to investigate arsenic body load in community residents and to examine the associated factors for both exposure and cardiovascular effects, we carried out a cross-sectional study of residents from industrial and non-industrial areas of middle Taiwan. A random sample, stratified for age (35-, 45- and 55-) and gender, was taken during 2002.09 ∼ 2003.03, using household surveys, where interviews were conducted by public health nurses. Clinicians performed heath checkups in health care units, where fasting venous blood samples were collected and blood pressure was measured. Total arsenic levels in hair, blood, and urine were quantified by inductive coupled plasma-mass spectrometry (ICP-MS), after standardized pre-treatment and quality control including assurance tests had been carried out. Results: Hair arsenic concentration, in the inorganic form, was significantly higher in industrial (0.06 μg/g hair) when compared to non-industrial (0.04 μg/g hair) areas (p=0.002). Use of underground water (odds ratio (OR)=1.97, p=0.003) and male gender (OR=15.4, p<0.001) are independent factors associated with increased arsenic level in hair, when considering occupation and life style of the subjects. Hair arsenic level was demonstrated to be an important predictor of metabolic syndrome, next to age and gender. The excess risk for arsenic load was most significant in the 35–44 age group. The pattern for the increased risk was similar for hypertension (OR=1.5, p=0.098), when all the potential risk factors were taken into consideration. Increased plasma glucose concentrations with increasing hair arsenic levels was profound in diabetic patients (r=0.25, p=0.05). Conclusion: This first report on internal arsenic exposure associated with increased risk of metabolic syndrome and hypertension in the community is worth noting, for the prevention of high prevalence of the diseases in industrialized countries.

Effect of feeding live yeast products to calves with failure of passive transfer on performance and patterns of antibiotic resistance in fecalEscherichia coli

Fifty-two newborn Holstein calves with serum IgG concentrations less than 0.73 g.dL(-1) were randomly assigned to one of four treatments: no added live yeast (control), 0.5 g of live yeast added to the grain for 84 d (SC; Saccharomyces cerevisiae), 0.5 g of live yeast added to the milk for 42 d (SB; S. cerevisiae, spp. boulardii), and 0.5 g of live yeast added to the grain for 84 d and to the milk for 42 d (SCSB). Calves were offered 440 g of milk replacer DM for the first 42 d and grain for ad libitum intake throughout the study. Plasma was analyzed weekly for concentrations of glucose and beta-hydroxybutyrate. Escherichia coli isolated from fecal samples collected every 2 weeks were used for determination of antibiotic resistance patterns. Calves receiving SC consumed more grain DM, had increased weight gain prior to weaning, and increased plasma glucose concentrations compared to controls. Days with diarrhea were reduced by feeding live yeast to calves. Antibiotic resistance in fecal E. coli was associated with the age of calves with highest levels of resistance observed in the 3 d calves. While calves receiving SCSB had higher levels of antibiotic resistance than controls, this effect was not associated with any of the other treatments. Improvements in performance of calves with failure of passive transfer were observed when live yeast was added only to the grain.

Effect of chemotherapy on circulating gastrointestinal hormone levels in ovarian cancer patients: Relationship to nausea and vomiting

ObjectiveThe introduction of 5-HT3 receptor antagonists greatly reduced the problems associated with nausea and vomiting immediately after cancer chemotherapy. However, delayed nausea and vomiting is still a major problem and the underlying mechanism is obscure.Material and methodsWe studied the effect of cisplatin-containing combination chemotherapy in 14 ovarian cancer patients on the levels of gastrin and a panel of other hormones as well as glucose and prostaglandin F2α. Blood samples were obtained once daily in the morning before chemotherapy and for 4 days after chemotherapy.ResultsConcentrations of many hormones including gastrin were generally high. A pronounced increase in plasma insulin levels occurred on the day after chemotherapy accompanied by a modest increase in plasma glucose concentrations. Minor increases were observed for gastrin, oxytocin and prostaglandin F2α. In contrast, a transient decrease after chemotherapy was observed for motilin. Plasma cortisol decreased markedly after chemotherapy as expected since betamethasone was given as an antiemetic prophylaxis. Certain trends concerning the relationship between some hormones and nausea and vomiting were noted. A high plasma gastrin concentration before chemotherapy was related to delayed vomiting. Relative day-to-day variability of cholecystokinin tended to correlate positively with delayed nausea, whereas an inverse relationship was observed for gastrin variability.ConclusionsChanges in hormone plasma levels were found but only few could be distinguished as possible mediators of delayed nausea and vomiting.

Repetitive postprandial hyperglycemia increases cardiac ischemia/reperfusion injury: prevention by the α‐glucosidase inhibitor acarbose

Protective effects of the alpha-glucosidase inhibitor acarbose have been reported for various diabetic complications. In the STOP-NIDDM study, even patients without overt diabetes, but with impaired glucose tolerance, had a reduction in cardiovascular events when treated with acarbose. Therefore, we investigated the effect of repetitive postprandial hyperglycemia on the cardiac ischemia/reperfusion injury in vivo. Mice were treated daily by single applications of placebo, sucrose (4 g/kg body weight), or sucrose + acarbose (10 mg/kg body weight) by gavage for 7 days. Acarbose treatment significantly reduced the sucrose-induced increase in plasma glucose concentration. Subsequently, animals underwent 30 min of ischemia by coronary artery ligation and 24 h of reperfusion in vivo. In the sucrose group, ischemia/reperfusion damage was significantly increased (infarct/area at risk, placebo vs. sucrose, 38.8+/-7.5% vs. 62.2+/-4.8%, P<0.05). This was prevented by acarbose treatment (infarct/area at risk 30.7+/-7.2%). While myocardial inflammation was similar in all groups, oxidative stress as indicated by a significant increase in lipid peroxides was enhanced in the sucrose, but not in the sucrose + acarbose group. In summary, repetitive postprandial hyperglycemia increases ischemia/reperfusion damage. This effect can be prevented by treatment with the alpha-glucosidase inhibitor acarbose.

Metabolic risk during antipsychotic treatment

Background: Compared with the general population, individuals with schizophrenia demonstrate an increased prevalence of obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD). Increased adiposity is associated with decreases in insulin sensitivity, leading to an increased risk of hyperglycemia and hyperlipidemia. Antipsychotic medications can increase adiposity, and a range of evidence from case reports, observational studies, retrospective database analyses, and controlled experimental studies (including randomized clinical trials) suggests that treatment with antipsychotic medications may be associated with an increased risk for insulin resistance, hyperglycemia, dyslipidemia, and T2DM. Objective: This article reviews current evidence for the hypothesis that treatment with antipsychotic medications may be associated with increased risks for weight gain, insulin resistance, hyperglycemia, dyslipidemia, and T2DM, and examines the relationship of adiposity to medical risk. Methods: Relevant publications were identified through a search of MEDLINE from 1975 to the present using the primary search parameters “diabetes or hyperglycemia or glucose or insulin or lipids” and “antipsychotic.” Meeting abstracts and earlier nonindexed articles concerning antipsychotic-associated weight gain and metabolic disturbance were also reviewed. Key studies in this emerging literature were summarized, including case reports, observational studies, retrospective database analyses, and controlled experimental studies. Results: Individual antipsychotic medications are associated with different degrees of treatment-induced increases in body weight and adiposity, ranging from modest effects (<2 kg) with amisulpride, ziprasidone, and aripiprazole to clinically significant increases with olanzapine (4–10 kg). In addition to strong evidence concerning the effect of adiposity on insulin sensitivity in nonpsychiatric populations, increased adiposity in patients with schizophrenia has been associated with decreases in insulin sensitivity; this and other effects may contribute to increases in plasma glucose concentrations and lipid levels. Conclusion: Metabolic changes in psychiatric patients who receive antipsychotic agents can contribute to the development of the metabolic syndrome and increase the risk for T2DM and CVD.

Effects of dexamethasone and colostrum feeding on mRNA levels and binding capacities of β-adrenergic receptors in the liver of neonatal calves

Glucocorticoids increase plasma glucose concentrations in neonatal calves, but not hepatic gluconeogenic enzyme mRNA levels and activities. Catecholamines, too, enhance plasma glucose levels and regulate hepatic glucose metabolism. We have measured hepatic mRNA levels of β-adrenergic receptors and β-adrenergic receptor binding in neonatal calves on day 5 of life. Calves were fed either colostrums (C) or an isoenergetic milk-based formula (F), and in each feeding group, half of the calves were treated with dexamethasone (DEXA; 30 μg/(kg body weight day)). Abundance of mRNA was highest ( P < 0.01) for β 2-adrenergic receptors and was higher ( P < 0.01) for β 1- than for β 3-adrenergic receptors. DEXA treatment decreased ( P < 0.05) β 1- and β 2-adrenergic receptor mRNA levels. β 3-Adrenergic receptor mRNA levels were higher ( P < 0.05) in colostrum- than in formula-fed calves. Competitive binding revealed highest affinities for alprenolol, propranolol (both β 1- and β 2-antagonists), and ICI-188,551 (β 2-antagonist), which did not significantly differ from each other. Atenolol (β 1-antagonist) up to 10 −5 M did not displace ( 3H)-CGP-12177 from receptors. Competitive binding for adrenaline was best fitted by a two-receptor model. DEXA decreased ( P < 0.05) ( 3H)-CGP-12177 binding capacities, whereas binding affinity of ( 3H)-CGP-12177 was not affected by DEXA or different feeding. Binding sites correlated positively with mRNA levels of β 2-adrenergic receptors ( r = 0.56; P < 0.01). In conclusion, β 2-adrenergic receptors were the dominant subtype in the hepatic tissue. Feeding did not significantly affect β 2-adrenergic binding sites. However, DEXA decreased β 2-adrenergic binding sites and this was regulated at the transcriptional level.

Effects of a single dose of dexamethasone-21 ‐ isonicotinate on the metabolism of heifers in early lactation

Eight Swedish crossbred heifers, about two-and-a-half years old, were given a single intramuscular dose of dexamethasone-21-isonicotinate between nine and 15 days after they had calved and eight similar heifers were...

Suprachiasmatic GABAergic inputs to the paraventricular nucleus control plasma glucose concentrations in the rat via sympathetic innervation of the liver.

Daily peak plasma glucose concentrations are attained shortly before awakening. Previous experiments indicated an important role for the biological clock, located in the suprachiasmatic nuclei (SCN), in the genesis of this anticipatory rise in plasma glucose concentrations by controlling hepatic glucose production. Here, we show that stimulation of NMDA receptors, or blockade of GABA receptors in the paraventricular nucleus of the hypothalamus (PVN) of conscious rats, caused a pronounced increase in plasma glucose concentrations. The local administration of TTX in brain areas afferent to the PVN revealed that an important part of the inhibitory inputs to the PVN was derived from the SCN. Using a transneuronal viral-tracing technique, we showed that the SCN is connected to the liver via both branches of the autonomic nervous system (ANS). The combination of a blockade of GABA receptors in the PVN with selective removal of either the sympathetic or parasympathetic branch of the hepatic ANS innervation showed that hyperglycemia produced by PVN stimulation was primarily attributable to an activation of the sympathetic input to the liver. We propose that the daily rise in plasma glucose concentrations is caused by an SCN-mediated withdrawal of GABAergic inputs to sympathetic preautonomic neurons in the PVN, resulting in an increased hepatic glucose production. The remarkable resemblance of the presently proposed control mechanism to that described previously for the control of daily melatonin rhythm suggests that the GABAergic control of sympathetic preautonomic neurons in the PVN is an important pathway for the SCN to control peripheral physiology.

Effects of exogenous glucose on brain ischemia in ovine fetuses.

We examined the effects of prolonged moderate hyperglycemia with and without an additional rapid glucose injection on ischemic brain injury in the fetus. Twenty-five ewes (117-124 d of gestation) were assigned to one of four groups: 1) glucose-infused fetuses exposed to 30 min of carotid artery occlusion followed by 48 h of reperfusion (I/R-Glu, n = 8); 2) glucose-infused plus rapid glucose injection given 100 min before 30 min of occlusion followed by 48 h of reperfusion (I/R-GluR, n = 4); 3) placebo-infused exposed to 30 min of occlusion and 48 h of reperfusion (I/R-PL, n = 8); and 4) glucose-infused sham occlusion and 48 h of sham reperfusion (control, n = 5). After baseline measurements, fetuses were infused with glucose (9-16 mg/kg/min) for 48 h before and after carotid occlusion or sham treatment. The I/R-PL group received 0.9% NaCl. Brain pathologic outcome was determined. Serial sections stained with Luxol fast blue-hematoxylin and eosin were scored for white matter, cerebral cortical, and hippocampal lesions. These areas received graded pathologic scores of 0 to 5, reflecting the amount of injury, where 0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, 4 = 76-95%, and 5 = 96-100% of the area damaged. Comparisons of the pathologic scores for cerebral cortex (CC), white matter (WM), and hippocampus (H) demonstrated that the I/R-GluR (CC: 4.56 +/- 0.11, WM: 4.50 +/- 0.11, H: 3.44 +/- 0.48, mean +/- SEM) had more (p < 0.05) damage than the I/R-Glu (CC: 2.46 +/- 0.47, WM: 1.97 +/- 0.37, H: 1.81 +/- 0.36) and control (CC: 1.12 +/- 0.13, WM: 0.82 +/- 0.34, H: 0.80 +/- 0.34) groups. The pathologic scores in the I/R-Glu were (p < 0.05) greater than the control, but not the I/R-PL (CC: 2.12 +/- 0.35, WM: 2.20 +/- 0.44, H: 1.59 +/- 0.41) group. We conclude that exposure to prolonged moderate hyperglycemia before ischemia and during reperfusion does not affect the extent of brain injury, but exposure to an additional acute increase in plasma glucose concentration before ischemia is extremely detrimental to the fetal brain.

Hyperglycemia associated with increased hepatic glycogen phosphorylase and phosphoenolpyruvate carboxykinase in rats following subchronic exposure to malathion

We examined the effects of subchronic exposure to malathion, an organophosphorous (OP) insecticide, on plasma glucose and hepatic enzymes of glycogenolysis and gluconeogenesis in rats in vivo. Malathion was administered orally at doses of 100, 200 and 400 ppm for 4 weeks. At the end of the specified treatment (18 h fasting after the last dose of malathion), the liver was removed. The activities of glycogen phosphorylase (GP) and phosphoenolpyruvate carboxykinase (PEPCK) were analyzed in the homogenate. Four weeks administration of malathion at doses of 100 ppm, 200 ppm, and 400 ppm increased plasma glucose concentrations by 25% ( P<0.01), 17% ( P<0.01), and 14% ( P<0.01) of control, respectively. Malathion also increased hepatic PEPCK activity by 25% (100 ppm, P<0.01), 16% (200 ppm, P<0.01), and 21% (400 ppm, P<0.01) of control, respectively. In addition, malathion increased hepatic GP by 22% (100 ppm, P<0.01), 41% (200 ppm, P<0.01), and 32% (400 ppm, P<0.01) of controls. We conclude that exposure of rats to malathion as a widely used OP in subchronic exposure, which resembles human exposure, may induce diabetes associated with stimulation of hepatic gluconeogenesis and glycogenolysis in favor of glucose release into the blood. The possible mechanisms including increased energy production to detoxification, depressed paraoxonase activity, and increased production of cyclic nucleotides are discussed.

Angiotensin II type-1 receptor blocker valsartan enhances insulin sensitivity in skeletal muscles of diabetic mice.

Angiotensin II has been shown to contribute to the pathogenesis of insulin resistance; however, the mechanism is not well understood. The present study was undertaken to investigate the potential effect of an angiotensin II type-1 (AT1) receptor blocker, valsartan, to improve insulin resistance and to explore the signaling basis of cross-talk of the AT1 receptor- and insulin-mediated signaling in type 2 diabetic KK-Ay mice. Treatment of KK-Ay mice with valsartan at a dose of 1 mg/kg per day, which did not influence systolic blood pressure, significantly increased insulin-mediated 2-[3H]deoxy-d-glucose (2-[3H]DG) uptake into skeletal muscle and attenuated the increase in plasma glucose concentration after a glucose load and plasma concentrations of glucose and insulin. In contrast, insulin-mediated 2-[3H]DG uptake into skeletal muscle was not influenced in AT2 receptor null mice, and an AT2 receptor blocker, PD123319, did not affect 2-[3H]DG uptake and superoxide production in skeletal muscle of KK-Ay mice. Moreover, we observed that valsartan treatment exaggerated the insulin-induced phosphorylation of IRS-1, the association of IRS-1 with the p85 regulatory subunit of phosphoinositide 3 kinase (PI 3-K), PI 3-K activity, and translocation of GLUT4 to the plasma membrane. It also reduced tumor necrosis factor-alpha (TNF-alpha) expression and superoxide production in skeletal muscle of KK-Ay mice. Specific AT1 receptor blockade increases insulin sensitivity and glucose uptake in skeletal muscle of KK-Ay mice via stimulating the insulin signaling cascade and consequent enhancement of GLUT4 translocation to the plasma membrane.

Inhibition of small-intestinal sugar absorption mediated by sodium orthovanadate Na3VO4in rats and its mechanisms

To investigate the inhibitory effects of sodium orthovanadate on small-intestinal glucose and maltose absorption in rats and its mechanism. Normal Wistar rats were lavaged with sodium orthovanadate (16 mg/kg, 4 mg/kg and 1 mg/kg) for 6 d. Blood glucose values were measured after fasting and 0.5, 1, 1.5 and 2 h after glucose and maltose feeding with oxidation-enzyme method. alpha-glucosidase was abstracted from the upper small intestine, and its activity was examined. mRNA expression of alpha-glucosidase and glucose-transporter 2 (GLUT2) in epithelial cells of the small intestine was observed by in situ hybridization. Sodium orthovanadate could delay the increase of plasma glucose concentration after glucose and maltose loading, area under curve (AUC) in these groups was lower than that in control group. Sodium orthovanadate at dosages of 10 micromol/L, 100 micromol/L and 1000 micromol/L could suppress the activity of alpha-glucosidase in the small intestine of normal rats, with an inhibition rate of 68.18%, 87.22% and 91.91%, respectively. Sodium orthovanadate reduced mRNA expression of alpha-glucosidase and GLUT2 in epithelial cells of small intestine. Sodium orthovanadate can reduce and delay the absorption of glucose and maltose. The mechanism may be that it can inhibit the activity and mRNA expression of alpha-glucosidase, as well as mRNA expression of GLUT2 in small intestine.

Dexamethasone and colostrum feeding affect hepatic gluconeogenic enzymes differently in neonatal calves.

Plasma glucose concentrations in neonates are influenced by colostrum feeding and by glucocorticoids. We have tested whether a high-glucocorticoid status after birth, as well as colostrum feeding, influences glucose metabolism in association with changes of hepatic expression and activities of gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) and pyruvate carboxylase (PC; EC 6.4.1.1) in neonatal calves. Calves (n = 14 per group) were fed either colostrum or a milk-based formula with nutrient and energy contents similar to colostrum. Half the calves in each feeding group were treated with dexamethasone (DEXA; 30 microg/[kg BW x d]). Pre- and postprandial blood samples were taken on d 1, 2, 4, and 5 and liver samples were collected on d 5 of life. Dexamethasone treatment increased (P < or = 0.05) plasma concentrations of glucose, insulin, and glucagon more in colostrum-fed than in formula-fed calves but increased (P < or = 0.05) urea concentrations and decreased (P < or = 0.05) concentrations of NEFA, ACTH, and cortisol independent of colostrum vs. formula feeding. Colostrum feeding increased (P < 0.05) plasma glucose, but decreased (P < 0.05) plasma urea concentrations. Glucagon-to-insulin ratios in DEXA-treated and colostrum-fed calves were decreased (P < 0.05). Dexamethasone treatment decreased hepatic mRNA levels and activities of PC (P < 0.001 and P < 0.10) and activities of PEPCK (P < 0.001) but increased (P < 0.001) the glycogen content. Colostrum feeding increased (P < 0.05) mitochondrial PEPCK mRNA levels and PEPCK activities in calves not treated with DEXA but decreased (P < 0.1) amounts of PC mRNA. In conclusion, increased plasma glucose concentrations after DEXA treatment were not associated with a stimulation of hepatic gluconeogenic enzyme activities; however, colostrum feeding probably raised plasma glucose concentrations because of increased hepatic gluconeogenic activities.

Effect of SOM230 a stable somatostatin analogue with a universal binding profile on GH, IGF-1 and glucose levels in rats

Somatostatin is expressed in many tissues throughout the body including the CNS, the gastrointestinal (GI) tract and the pancreas. Somatostatin exerts effects on target cells via activation of 5 SRIF receptors (sst1 to sst5) and inhibits effectively growth hormone and insulin-like growth factor-I (IGF-I) release. Natural somatostatins (SRIF 14 or 28) bind with high affinity to all sst receptors, however their use is limited by the rapid proteolytic degradation in plasma (t½ ≤3min). The octapeptide Sandostatin (SMS 201–995) is successfully used in 2/3 of acromegaly patients and patients with gastroenteropancreatic (GEP) tumors, although desensitization of the inhibitory response occurs in GEP tumor patients after prolonged treatment. SOM230 is a new SRIF analog which binds with nanomolar affinity to sst1–3 and sst5. In short term (1h) rat experiments SOM230 and SMS 201–995 inhibit GH release with similar potency; however, the inhibitory effect of SOM230 on GH release was 4-fold more potent at 6h post injection than SMS 201–995, indicating its increased metabolic stability. In fact, PK studies in rats demonstrated a plasma half-life of SOM230 of 23h, as compared to 2h for SMS 201–995. The improved metabolic stability of SOM230 was confirmed in monkeys and humans. Continuous treatment of rats with SOM230 at 10µg/kg/h, decreased IGF-1 plasma levels on day 2 by 90% while under SMS 201–995 treatment plasma IGF-1 levels decreased only by 49%. After a 2-week infusion of somatostatin analogue in rats the suppression of GH and IGF-1 levels by SOM230 was still pronounced, while the response to SMS 201–995 was largely lost. This enhanced effect of SOM230 on IGF-1 plasma levels was confirmed in an 8-week study where both analogs were infused at the high dose of 50µg/kg/h in rats. The marked suppression of plasma IGF-1 levels corresponded with potent inhibition of body weight gain of rats. In acute studies in Rhesus monkey, SOM230 and SMS 201–995 treatment resulted in GH inhibition at 1h with ID50 values of 0.5 and 0.4µg/kg respectively, but plasma IGF-1 levels were only lowered by SOM230 at this early time point (-53% at 24h post injection). In Cynomolgus monkeys a 2-week infusion of SOM230, but to a much lesser extent SMS 201–995, lowered plasma GH levels significantly (from 16.3 to 1.8 ng/ml). At 10µg/kg s.c. SOM230 caused a marked increase in glucose concentration 1h after dosing, whereas after 6h the glucose levels were back at control values. Lower doses and SMS 201–995 at all doses did not increase plasma glucose concentrations at any time point. In long-term studies 10µg/kg/h s.c. SOM230 had no effect on basal glucose levels after more than 14 days of dosing. The transient increase in plasma glucose concentration in rats is not observed in dogs, mice and monkeys and is in line with a strong inhibition of insulin secretion in rats. In conclusion, SOM230 has a unique structure, binds almost universally to human sst's and inhibits potently the GH/IGF-1 axis in various species. SOM230 is currently being evaluated in healthy volunteers and acromegalic patients.

Effects of Casein and Glucose on Responses of Cows Fed Diets Based on Restrictively Fermented Grass Silage

This study was conducted to investigate whether well fed dairy cows given restrictively fermented grass silage diet will respond to incremental glucose and amino acid supply at early stage of lactation. Four rumen-cannulated Finnish Ayrshire cows were used in a 4×4 Latin square experiment with 14-d periods. The cows were fed good quality restrictively fermented grass silage ensiled with a formic acid additive for ad libitum intake. A concentrate mixture consisting of barley (85%) and solvent extracted rapeseed meal (11.4%) was given at a rate of 9 kg/d. The four treatments were continuous abomasal infusions of water (control), casein 300g/d, glucose 300g/d, and casein 300g/d + glucose 300g/d. The infusions had only minor effects on feed intake, diet digestibility, or rumen fermentation pattern. Both casein and glucose infusions increased milk, protein and lactose yields the effects being partly additive on the combined infusion. Infused casein increased milk protein and urea as well as plasma urea concentrations. Both casein and glucose tended to increase plasma glucose concentration. Casein increased arterial plasma concentrations of essential amino acids (EAA), branched-chain AA (BCAA), and total AA (TAA). Both casein and glucose, although glucose usually less than casein, increased arteriovenous differences of EAA, nonessential AA, BCAA, and TAA. Extraction efficiencies of AA were higher for glucose than for casein. Mammary plasma flow was at highest on the control diet, but reduced owing to infused nutrients, the reduction being less with combined rather than separate infusions of casein and glucose. Based on the partly additive increases in milk production parameters and changes in plasma metabolites, it is suggested that glucose alone increased milk protein yield by sparing AA from hepatic utilization, while casein increased both supply of AA and glucose. It was concluded that cows at early stage of lactation fed diets comprising of restrictively fermented grass silage and a cereal-based concentrate suffer from both limited AA and glucose supplies.

Residual C-peptide secretion and endothelial function in patients with Type II diabetes

Recent studies have demonstrated that C-peptide exerts beneficial effects on endothelial function. To investigate the relationship between residual pancreatic C-peptide secretion and endothelial function in patients with well controlled or poorly controlled Type II diabetes, we studied 100 patients with Type II diabetes that were free from diabetic neuropathy. In all patients, insulin resistance, residual pancreatic C-peptide secretion, endothelial function and oxidative stress were investigated using the homoeostasis model assessment (HOMA) index, glucagon bolus test, brachial reactivity, Trolox equivalent antioxidant capacity (TEAC) and thiobarbituric acid-reacting substances (TBARS). The patients were categorized into quartiles on the basis of plasma HbA(1c) (glycated haemoglobin) concentration. Analysis of the data showed significant increases in plasma glucose concentration, HOMA index, microalbuminuria and TBARS, and significant decreases in plasma C-peptide, AUC (area under the curve) plasma C-peptide and TEAC, through the different quartiles (from the lowest to the highest HbA(1c) concentration). With regard to parameters of endothelial function, changes in diameter showed a significant declining trend through the different quartiles. Endothelial-dependent changes in diameter were independently and significantly associated with AUC C-peptide levels, TEAC and TBARS. In conclusion, our study demonstrated that patients with Type II diabetes with good residual C-peptide secretion are better protected from endothelial dysfunction that those with poor C-peptide secretion.

Glycemic responses in white sturgeon after oral administration of graded doses of d-glucose

Oral glucose tolerance tests, using a technique that combined esophageal intubation, dorsal aorta cannulation and urinary catheterization, were performed to assess the ability of white sturgeon to utilize different doses of d -glucose (0, 250, 500, 750, 1000, 1250 and 1500 mg·kg −1 body weight (BW)). In fish intubated with 0 mg glucose·kg −1 BW, plasma glucose concentrations did not change significantly during the 24-h experimental period (4.3±0.1 mmol·l −1 , mean±S.E., n =40 (5 fish and 8 time points), P >0.05). Observed maximum plasma glucose concentrations (8.4±0.4 and 10.1±0.8 mmol·l −1 , n =5) were detected at 3–4 h post-intubation in fish given 1250 and 1500 mg glucose·kg −1 BW, respectively ( P <0.05). White sturgeon dosed with 500, 750, 1000, 1250 and 1500 mg glucose·kg BW −1 showed a persistent hyperglycemia not corrected until 12–24 h post-intubation. Compartmental modeling of plasma glucose kinetics indicated that the rate constant for glucose absorption from the digestive tract into the bloodstream was significantly reduced, indicating that glucose absorption into the circulation was non-linearly related to dose, and became saturated at higher dosages. In contrast, glucose clearance rate increased with increasing plasma glucose concentration, but the rate of gluconeogenesis appeared to decrease only slightly. The small reduction in gluconeogenesis may contribute to the prolonged hyperglycemia observed in sturgeon after a glucose load.

Extent of Hypophagia Caused by Propionate Infusion Is Related to Plasma Glucose Concentration in Lactating Dairy Cows

Two experiments were conducted to evaluate how dose-response effects of intraruminal infusion of propionate on feeding behavior and plasma metabolites are altered by diets differing in fermentability. Twelve ruminally cannulated Holstein cows were used in each experiment. Cows were fed diets containing either steam flaked corn or dry cracked corn (30% of dietary dry matter) in expt. 1, and diets differing in forage-to-concentrate ratio (66:34 vs. 36:64) in expt. 2. For both experiments, the experimental design was a crossover for dietary treatment, and a 6 x 6 Latin square for infusion treatment within a diet for each period. Infusion treatments were mixtures of sodium propionate and sodium acetate, containing propionate at 0, 0.2, 0.4, 0.6, 0.8 and 1.0 as a fraction of total volatile fatty acids infused. Treatment solutions were infused into the rumen continuously for 18 h starting 6 h before feeding at a rate of 23.1 mmol/min. Although propionate production from ruminal fermentation was expected to be different, dietary treatments did not affect dry matter intake (DMI) responses to propionate infusion for either experiment. However, propionate infusion decreased DMI linearly in expt. 1, but did not decrease DMI at lower rates of propionate infusion, which were much more effective at increasing plasma glucose concentration in expt. 2. Propionate had a smaller hypophagic effect at low concentrations of plasma glucose and had a greater hypophagic effect at elevated concentrations of plasma glucose, which could be explained by changes in the metabolism of propionate in the liver.

Daily rhythms in glucose metabolism: suprachiasmatic nucleus output to peripheral tissue.

The body has developed several control mechanisms to maintain plasma glucose concentrations within strict boundaries. Within those physiological boundaries, a clear daily rhythm in plasma glucose concentrations is present; this rhythm depends on the biological clock, which is located in the hypothalamic suprachiasmatic nucleus (SCN), and is independent of the daily rhythm in food intake. Interestingly, there is also a daily rhythm in glucose uptake, which also depends on the SCN and follows the same pattern as the daily rhythm in plasma glucose concentrations; both rise before the onset of activity. Thus, the SCN prepares the individual for the upcoming activity period in two different ways: by increasing plasma glucose concentrations and by facilitating tissue glucose uptake. In addition to this anticipation of glucose metabolism to expected glucose demands, the SCN also influences, depending on the time of the day, the responses of pancreas and liver to abrupt glucose changes (such as a glucose rise after a meal or hypoglycaemia). This review presents the view that the SCN uses different routes to (i) maintain daily glucose balance and (ii) set the level of the endocrine response to abrupt blood glucose changes.

Perioperative Glucose Infusion and the Catabolic Response to Surgery: The Effect of Epidural Block

Although the nitrogen-sparing properties of epidural block and IV glucose on the days after surgical trauma have been well established, their metabolic effects during the acute phase of the stress response remain unclear. Therefore, in this study we investigated the effect of epidural block on glucose and protein kinetics during and immediately after surgery in patients receiving IV glucose at 2 mg · kg−1 · min−1. Sixteen patients undergoing colorectal surgery received either general anesthesia with epidural block with bupivacaine (EDA;n = 8) or general anesthesia alone (control;n = 8). Glucose and protein kinetics were determined during and 2 h after the operation by stable isotope tracers [6,6-2H2]glucose and L-[1-13C]leucine. Plasma concentrations of glucose, insulin, cortisol, and glucagon were also determined. Epidural block attenuated the perioperative increase in plasma glucose concentration (P < 0.05). The rate of appearance of glucose (Ra glucose) and endogenous glucose production (EGP) were slower in the EDA group than in control subjects during (Ra glucose, EDA 13.2 ± 1.0 versus control 15.3 ± 1.8 μmol · kg−1 · min−1;P < 0.05; EGP, EDA 1.2 ± 1.2 versus control 3.8 ± 1.7 μmol · kg−1 · min−1;P < 0.05) and after the operation (P > 0.05). Whereas protein breakdown and amino acid oxidation decreased in both groups (P < 0.05), whole-body protein synthesis remained unchanged. Insulin levels increased with both anesthetic techniques (P < 0.05). Intraoperative plasma concentrations of cortisol and glucagon were smaller in the EDA group (P < 0.05). The intraoperative suppression of EGP by exogenous glucose was more pronounced in the presence of epidural block. However, epidural block failed to exert a protein-sparing effect during the acute phase of the stress response in patients receiving IV glucose.