Lower Plasma Glucose Concentrations Research Articles

Caloric restriction alters galanin and its receptor in hypothalamus of wistar rats

Caloric restriction (CR) reverses obesity and insulin resistance, yet the detailed mechanism underlying its beneficial effects is poorly understood. The galanin system is closely associated with energy metabolism. It is yet unclear whether this effect of CR is operating through the regulation of the galanin system. To test this effect, we subjected rats to either 60% or 40% calorie restriction for one week. After the one-week's experiment, galanin and many genes associated with the function of metabolism were examined. The present findings showed that 7 days of 60% or 40% calorie restriction lowered body weight and plasma glucose concentration in rats, suggesting that rats under CR have improved weight loss and systemic glucose metabolism. Besides, the lower plasma glucose was associated with an increase in muscle glucose uptake resulting from elevations of both glucose transporter 4 (GLUT4) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in skeletal muscles. Moreover, the levels of galanin and its receptors (GALR1-3) mRNA markedly increased in the hypothalamus of CR rats. Taken together, these results supported that non-pharmacological activation of the galanin/GALR signaling with CR regimen led to activation of the PGC-1α/GLUT4 axis in skeletal muscles which can enhance energy metabolism. The current findings provide additional evidence that galanin is a critical factor for CR-induced weight loss and metabolic changes. CR regimen may be recognized as a non-pharmacological intervention that could prevent obesity and its associated metabolic disorders.

Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health.

IntroductionWhile oral glucose ingestion typically leads to a decrease in circulating glucagon levels, a substantial number of persons display stable or rising glucagon concentrations when assessed by radioimmunoassay (RIA). However, these assays show cross-reactivity to other proglucagon cleavage products. Recently, more specific assays became available, therefore we systematically assessed glucagon and other proglucagon cleavage products and their relation to metabolic health.Research Design and MethodsWe used samples from 52 oral glucose tolerance tests (OGTT) that were randomly selected from persons with different categories of glucose tolerance in an extensively phenotyped study cohort.ResultsGlucagon concentrations quantified with RIA were non-suppressed at 2 hours of the OGTT in 36% of the samples. Non-suppressors showed lower fasting glucagon levels compared to suppressors (p=0.011). Similar to RIA measurements, ELISA-derived fasting glucagon was lower in non-suppressors (p<0.001). Glucagon 1-61 as well as glicentin and GLP-1 kinetics were significantly different between suppressors and non-suppressors (p=0.004, p=0.002, p=0.008 respectively) with higher concentrations of all three hormones in non-suppressors. Levels of insulin, C-peptide, and free fatty acids were comparable between groups. Non-suppressors were leaner and had lower plasma glucose concentrations (p=0.03 and p=0.047, respectively). Despite comparable liver fat content and insulin sensitivity (p≥0.3), they had lower 2-hour post-challenge glucose (p=0.01).ConclusionsGlucagon 1-61, glicentin and GLP-1 partially account for RIA-derived glucagon measurements due to cross-reactivity of the assay. However, this contribution is small, since the investigated proglucagon cleavage products contribute less than 10% to the variation in RIA measured glucagon. Altered glucagon levels and higher post-challenge incretins are associated with a healthier metabolic phenotype.

Acute Effects of Kawakawa (Piper excelsum) Intake on Postprandial Glycemic and Insulinaemic Response in a Healthy Population.

Background: Piper excelsum (kawakawa) is an endemic shrub of Aotearoa, New Zealand, of cultural and medicinal importance to Māori. Its fruits and leaves are often consumed. These tissues contain several compounds that have been shown to be biologically active and which may underpin its putative health-promoting effects. The current study investigates whether kawakawa tea can modulate postprandial glucose metabolism. Methods: We report a pilot three-arm randomized crossover study to assess the bioavailability of kawakawa tea (BOKA-T) in six male participants with each arm having an acute intervention of kawakawa tea (4 g/250 mL water; 1 g/250 mL water; water) and a follow-up two-arm randomized crossover study to assess the impact of acute kawakawa tea ingestion on postprandial glucose metabolism in healthy human volunteers (TOAST) (4 g/250 mL water; and water; n = 30 (15 male and 15 female)). Participants consumed 250 mL of kawakawa tea or water control within each study prior to consuming a high-glycemic breakfast. Pre- and postprandial plasma glucose and insulin concentrations were measured, and the Matsuda index was calculated to measure insulin sensitivity. Results: In the BOKA-T study, lower plasma glucose (p < 0.01) and insulin (p < 0.01) concentrations at 60 min were observed after consumption of a high-dose kawakawa tea in comparison to low-dose or water. In the TOAST study, only plasma insulin (p = 0.01) was lower at 60 min in the high-dose kawakawa group compared to the control group. Both studies showed a trend towards higher insulin sensitivity in the high-dose kawakawa group compared to water only. Conclusions: Consuming kawakawa tea may modulate postprandial glucose metabolism. Further investigations with a longer-term intervention study are warranted.

BIOCHEMICAL IMPLICATIONS OF ORAL ADMINISTRATION OF EXTRACTS OF Acalypha wilkesiana LEAVES IN RABBITS

Thus, this study was conducted to evaluate the biochemical implications of oral administration of extracts of Acalypha wilkesiana leaves, using some serum parameters, in normal experimental rabbits. A total of eighteen (18) rabbits were randomized into three groups (A, B and C) of six animals each and treated with aqueous (A) and ethanol (B) extracts of Acalypha wilkesiana leaves. The extracts were administered orally at a dose of 300mg/kg body weight for a period of twenty-one (21) days. Group C animals served as control.Data are represented as Mean ± S.E.M (n = 6). Significance of Difference was tested by ANOVA at P &lt; 0.05.Administration of the aqueous or ethanol extract, at a dose of 300 mg/kg body weight, to normal rabbits resulted in a significantly (P &lt; 0.05) lower plasma glucose concentration. Treatment with the aqueous or ethanol extract resulted in a non-significantly (P &gt; 0.05) higher serum albumin, HDL-cholesterol and a non-significantly (P &gt; 0.05) lower serum total protein, globulin, triglycerides, LDL-cholesterol, as compared with the control, in normal rabbits. However, treatment with the ethanol extract resulted in a non-significantly (P &gt; 0.05) higher total cholesterol, while treatment with the aqueous extract resulted in a non-significantly (P &gt; 0.05) lower total cholesterol of the normal rabbits, as compared with the control. This shows that, the aqueous or ethanol extracts have hypoglycaemic and hypocholesterolemic effects on the rabbits.

Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis.

SignificanceMetformin is the most commonly prescribed drug for the treatment of type 2 diabetes mellitus, yet the mechanism by which it lowers plasma glucose concentrations has remained elusive. Most studies to date have attributed metformin's glucose-lowering effects to inhibition of complex I activity. Contrary to this hypothesis, we show that inhibition of complex I activity invitro and invivo does not reduce plasma glucose concentrations or inhibit hepatic gluconeogenesis. We go on to show that metformin, and the related guanides/biguanides, phenformin and galegine, inhibit complex IV activity at clinically relevant concentrations, which, in turn, results in inhibition of glycerol-3-phosphate dehydrogenase activity, increased cytosolic redox, and selective inhibition of glycerol-derived hepatic gluconeogenesis both invitro and invivo.

Maternal supply of a source of omega-3 fatty acids and methionine during late gestation on the offspring's growth, metabolism, carcass characteristic, and liver's mRNA expression in sheep.

The objective of the present experiment was to evaluate the effect of maternal supplementation with fatty acids (FAs) and methionine (Met) during late gestation on offspring growth, energy metabolism, plasma resolvin (RvD1) concentration, carcass characteristics, and hepatic mRNA expression. Ewes (5 pens/treatment; 3 ewes/pen) blocked by body weight (BW) were assigned to one of four treatments from day 100 of gestation until lambing. The treatments were: basal diet (NS) without FAs or Met supplementation; FA supplementation (FS; 1.01 % of Ca salts, containing n-3 FA); Met supplementation (MS; 0.1 % of rumen-protected methionine); and FS and MS (FS-MS). At birth (day 0), ewes and lambs were placed in a common pen. On day 60, lambs were weaned, sorted by sex, blocked by BW, and placed on a common finishing diet for 54 d (FP). A lamb per pen was used for a glucose tolerance test (GTT) after the FP. Carcass characteristics were recorded on day 56. Lamb data were analyzed as a randomized complete block design with a 2 × 2 × 2 factorial arrangement, with repeated measurements when needed (SAS 9.4). At weaning, lambs born to MS- or FS-fed ewes were heavier than lambs born from FS-MS ewes (FS × MS × Time; P = 0.02). A marginal significant FS × MS interaction (P = 0.09) was also observed on RvD1; lambs born to ewes in the NS and FS-MS treatments showed a lower RvD1 plasma concentration when compared with lambs born to FS- or MS-fed ewes. Lambs born to dams fed FA showed an increase (P = 0.05) in liver COX-2 mRNA relative expression. Lambs born to ewes supplemented with Met showed an increase (P = 0.03) in liver FABP4 mRNA expression. An FS × MS × Time interaction (P = 0.07) was observed in plasma glucose during the GTT; lambs born from FS-fed ewes showed lower plasma glucose concentration than lambs born to Met-supplemented ewes at 2 min after bolus administration. During the GTT, a marginal significant effect (P = 0.06) was observed for the lamb average insulin concentration due to maternal Met supplementation during late gestation, where these lambs had the lowest plasma concentration. Contrary to our hypothesis, the interaction of FA and Met supplementation during late gestation did not show a greater positive effect on offspring postnatal growth and metabolism. However, the individual supplementation of each nutrient has an effect on offspring development with a concomitant change in markers involved in the inflammatory response and energy metabolism.

Predicting the response to SGLT-2 inhibitors as add-on therapy to multiple day injection insulin with glycated albumin: a pilot study.

Achieving optimal glycemic targets is the main therapeutic goal in patients with type 2 diabetes (T2D) mellitus. HbA1c is the reference biomarker for monitoring glycemic control; however, in specific conditions affecting erythrocyte turnover or in patients on multiple daily injection (MDI) insulin regimens, the determination of glycated albumin (GA) may be preferable. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors represent a novel class of antidiabetic drugs that lower plasma glucose concentrations quickly, with insulin-independent mechanisms. Herein, we explored the role of GA in predicting the short-term response to SGLT-2 inhibitors as add-on to MDI insulin. Sixteen patients with long-standing, poorly controlled T2D on MDI insulin starting an SGLT-2 inhibitor were subjected to plasma GA and HbA1c measurements at 30 days intervals for up to 3 months in order to examine the temporal changes of these glycemic biomarkers. At the end of the study, grossly coincident with the life span of erythrocytes, a significant decrease in median HbA1c was observed, (from 8.7 [range: 8.2-9.3%] at baseline to 7.2 [range: 7.0-7.9%]), with the advantage of less insulin dose requirements. However, significant, and incremental reductions in median GA determinations could be already evident after 30 days (-3.5 [range: -7.5, -2.5%]) and 60 days (-6.4 [range: -10.5, -4.7%]) from the start of SGLT-2 inhibitor treatment and persisted for up to 3 months (-8.6 [range: -12.1, 6.1%]). The decrements of HbA1c observed at the 3-month visit were highly correlated with the concurrent absolute reductions of plasma GA (ρ=0.550, P=0.027), whereas a borderline significance could be demonstrated with reference to reductions in plasma GA at 30 and 60 days. Although limited by the small number of participants, these preliminary findings suggest that GA, rather than HbA1c, could represent a useful and reliable biomarker in T2D to monitor the early glucose-lowering effects of antidiabetic drugs with rapid onset of action, such as SGLT-2 inhibitors and MDI insulin.

Differential Effects of One Meal per Day in the Evening on Metabolic Health and Physical Performance in Lean Individuals.

Background: Generally, food intake occurs in a three-meal per 24 h fashion with in-between meal snacking. As such, most humans spend more than ∼ 12–16 h per day in the postprandial state. It may be reasoned from an evolutionary point of view, that the human body is physiologically habituated to less frequent meals. Metabolic flexibility (i.e., reciprocal changes in carbohydrate and fatty acid oxidation) is a characteristic of metabolic health and is reduced by semi-continuous feeding. The effects of time-restricted feeding (TRF) on metabolic parameters and physical performance in humans are equivocal.Methods: To investigate the effect of TRF on metabolism and physical performance in free-living healthy lean individuals, we compared the effects of eucaloric feeding provided by a single meal (22/2) vs. three meals per day in a randomized crossover study. We included 13 participants of which 11 (5 males/6 females) completed the study: age 31.0 ± 1.7 years, BMI 24.0 ± 0.6 kg/m2 and fat mass (%) 24.0 ± 0.6 (mean ± SEM). Participants consumed all the calories needed for a stable weight in either three meals (breakfast, lunch and dinner) or one meal per day between 17:00 and 19:00 for 11 days per study period.Results: Eucaloric meal reduction to a single meal per day lowered total body mass (3 meals/day –0.5 ± 0.3 vs. 1 meal/day –1.4 ± 0.3 kg, p = 0.03), fat mass (3 meals/day –0.1 ± 0.2 vs. 1 meal/day –0.7 ± 0.2, p = 0.049) and increased exercise fatty acid oxidation (p < 0.001) without impairment of aerobic capacity or strength (p > 0.05). Furthermore, we found lower plasma glucose concentrations during the second half of the day during the one meal per day intervention (p < 0.05).Conclusion: A single meal per day in the evening lowers body weight and adapts metabolic flexibility during exercise via increased fat oxidation whereas physical performance was not affected.

Optimal Responses to Constrained Bolus Inputs to Models of T1D

We characterise the bolus insulin input which minimises the maximum plasma glucose concentration predicted by the Magdelaine and Bergman minimal models in response to any positive bounded disturbance whilst remaining above a fixed lower plasma glucose concentration. This characterisation is in terms of the maxima and minima of the plasma glucose concentration and limits the controllability of such systems. Any further attempt to lower the maximum plasma glucose concentration will result in hypoglycaemia.

Euglycemic Ketoacidosis as a Complication of SGLT2 Inhibitor Therapy.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are drugs designed to lower plasma glucose concentration by inhibiting Na+-glucose-coupled transport in the proximal tubule. Clinical trials demonstrate these drugs have favorable effects on cardiovascular outcomes to include slowing the progression of CKD. Although most patients tolerate these drugs, a potential complication is development of ketoacidosis, often with a normal or only a minimally elevated plasma glucose concentration. Inhibition of sodium-glucose cotransporter-2 in the proximal tubule alters kidney ATP turnover so that filtered ketoacids are preferentially excreted as Na+ or K+ salts, leading to indirect loss of bicarbonate from the body and systemic acidosis under conditions of increased ketogenesis. Risk factors include reductions in insulin dose, increased insulin demand, metabolic stress, low carbohydrate intake, women, and latent autoimmune diabetes of adulthood. The lack of hyperglycemia and nonspecific symptoms of ketoacidosis can lead to delays in diagnosis. Treatment strategies and various precautions are discussed that can decrease the likelihood of this complication.

Increased body fat content in horses alters metabolic and physiological exercise response, decreases performance, and increases locomotion asymmetry.

ABSTRACTThis study examined the effect of altered body weight (BW) and body fat content on exercise performance and recovery. Nine horses were divided into two groups, and changes in BW and fat content were induced by feeding a high (HA) or restricted (RA) energy allowance for 36 days in a cross‐over design. In the last week of each treatment, BW and body condition score (BCS) were recorded, body fat percentage was estimated using ultrasound, and a standardized incremental treadmill exercise test (SET) and competition‐like field test were performed (scored by judges blinded to treatments). Blood samples were collected, and heart rate (HR), rectal temperature (RT), and respiratory rate (RR) were also recorded. Objective locomotion analyses were performed before and after the field test. Body weight, body fat percentage, and BCS were higher (5–8%) in HA than in RA horses (p < 0.05). In SET, HA horses showed higher HR, plasma lactate concentration, RR, and RT than RA horses (p < 0.05), and lower VLa4, hematocrit (Hct), plasma glucose, and plasma NEFA concentrations (p < 0.05). Hct was also lower in HA horses in the field test, while RA horses showed higher scores (p < 0.05). After both tests, resting plasma lactate concentrations were reached faster in RA than in HA horses (p < 0.05). Objective locomotion asymmetry was higher in HA than in RA (p < 0.05). These results clearly show that increased BW and body fat content in horses lower physiological fitness in terms of VLa4, plasma lactate removal, Hct levels, plasma glucose availability and reduce true performance evaluated by blinded judges.

Associations of Reduced Ambient PM2.5 Level With Lower Plasma Glucose Concentration and Decreased Risk of Type 2 Diabetes in Adults: A Longitudinal Cohort Study.

It remains unknown whether reduced air pollution levels can prevent type 2 diabetes mellitus. In this study, we investigated the associations between dynamic changes in long-term exposure to ambient fine particulate matter, defined as particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5), and changes in fasting plasma glucose (FPG) levels and incidence of type 2 diabetes. A total of 151,398 adults (ages ≥18 years) were recruited in Taiwan between 2001 and 2014. All participants were followed up for a mean duration of 5.0 years. Change in PM2.5 (ΔPM2.5) was defined as the value at a follow-up visit minus the corresponding value at the immediately preceding visit. The PM2.5 concentration in Taiwan increased during 2002-2004 and began to decrease in 2005. Compared with participants with little or no change in PM2.5 exposure, those with the largest decrease in PM2.5 had a decreased FPG level (β = -0.39, 95% confidence interval: -0.47, -0.32) and lower risk of type 2 diabetes (hazard ratio=0.86, 95% confidence interval: 0.80, 0.93). The sensitivity analysis and analyses stratified by sex, age, body mass index, smoking, alcohol drinking, and hypertension generally yielded similar results. Improved PM2.5 air quality is associated with a better FPG level and a decreased risk of type 2 diabetes development.

Effects of Manipulating Circulating Bile Acid Concentrations on Postprandial GLP-1 Secretion and Glucose Metabolism After Roux-en-Y Gastric Bypass.

BackgroundAltered bile acid (BA) turnover has been suggested to be involved in the improved glucose regulation after Roux-en-Y gastric bypass (RYGB), possibly via stimulation of GLP-1 secretion. We investigated the role of exogenous as well as endogenous BAs for GLP-1 secretion after RYGB by administering chenodeoxycholic acid (CDCA) and the BA sequestrant colesevelam (COL) both in the presence and the absence of a meal stimulus.MethodsTwo single-blinded randomized cross-over studies were performed. In study 1, eight RYGB operated participants ingested 200 ml water with 1) CDCA 1.25 g or 2) CDCA 1.25 g + colesevelam 3.75 g on separate days. In study 2, twelve RYGB participants ingested on separate days a mixed meal with addition of 1) CDCA 1.25 g, 2) COL 3.75 g or 3) COL 3.75 g × 2, or 4) no additions.ResultsIn study 1, oral intake of CDCA increased circulating BAs, GLP-1, C-peptide, glucagon, and neurotensin. Addition of colesevelam reduced all responses. In study 2, addition of CDCA enhanced meal-induced increases in plasma GLP-1, glucagon and FGF-19 and lowered plasma glucose and C-peptide concentrations, while adding colesevelam lowered circulating BAs but did not affect meal-induced changes in plasma glucose or measured gastrointestinal hormones.ConclusionIn RYGB-operated persons, exogenous CDCA enhanced meal-stimulated GLP-1 and glucagon secretion but not insulin secretion, while the BA sequestrant colesevelam decreased CDCA-stimulated GLP-1 secretion but did not affect meal-stimulated GLP-1, C-peptide or glucagon secretion, or glucose tolerance. These findings suggest a limited role for endogenous bile acids in the acute regulation of postprandial gut hormone secretion or glucose metabolism after RYGB.

Reduced glucose-stimulated insulin secretion following a 1-wk IGF-1 infusion in late gestation fetal sheep is due to an intrinsic islet defect.

Insulin and insulin-like growth factor-1 (IGF-1) are fetal hormones critical to establishing normal fetal growth. Experimentally elevated IGF-1 concentrations during late gestation increase fetal weight but lower fetal plasma insulin concentrations. We therefore hypothesized that infusion of an IGF-1 analog for 1 wk into late gestation fetal sheep would attenuate fetal glucose-stimulated insulin secretion (GSIS) and insulin secretion in islets isolated from these fetuses. Late gestation fetal sheep received infusions with IGF-1 LR3 (IGF-1, n = 8), an analog of IGF-1 with low affinity for the IGF binding proteins and high affinity for the IGF-1 receptor, or vehicle control (CON, n = 9). Fetal GSIS was measured with a hyperglycemic clamp (IGF-1, n = 8; CON, n = 7). Fetal islets were isolated, and insulin secretion was assayed in static incubations (IGF-1, n = 8; CON, n = 7). Plasma insulin and glucose concentrations in IGF-1 fetuses were lower compared with CON (P = 0.0135 and P = 0.0012, respectively). During the GSIS study, IGF-1 fetuses had lower insulin secretion compared with CON (P = 0.0453). In vitro, glucose-stimulated insulin secretion remained lower in islets isolated from IGF-1 fetuses (P = 0.0447). In summary, IGF-1 LR3 infusion for 1 wk into fetal sheep lowers insulin concentrations and reduces fetal GSIS. Impaired insulin secretion persists in isolated fetal islets indicating an intrinsic islet defect in insulin release when exposed to IGF-1 LR3 infusion for 1 wk. We speculate this alteration in the insulin/IGF-1 axis contributes to the long-term reduction in β-cell function in neonates born with elevated IGF-1 concentrations following pregnancies complicated by diabetes or other conditions associated with fetal overgrowth.NEW & NOTEWORTHY After a 1-wk infusion of IGF-1 LR3, late gestation fetal sheep had lower plasma insulin and glucose concentrations, reduced fetal glucose-stimulated insulin secretion, and decreased fractional insulin secretion from isolated fetal islets without differences in pancreatic insulin content.

No changes in fasting and 24-hour glucose levels in type 2 diabetic subjects observed after 10 days of L-Isoleucine supplementation

Rationale: Isoleucine (ILE) is known to modulate glucose metabolism, but it remains unclear if daily ILE supplementation is able to lower fasting and 24-hour plasma glucose concentrations in patients with type 2 diabetes (T2D).

The Role of Glucagon in the Acute Therapeutic Effects of SGLT2 Inhibition.

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) effectively lower plasma glucose (PG) concentration in patients with type 2 diabetes, but studies have suggested that circulating glucagon concentrations and endogenous glucose production (EGP) are increased by SGLT2i, possibly compromising their glucose-lowering ability. To tease out whether and how glucagon may influence the glucose-lowering effect of SGLT2 inhibition, we subjected 12 patients with type 2 diabetes to a randomized, placebo-controlled, double-blinded, crossover, double-dummy study comprising, on 4 separate days, a liquid mixed-meal test preceded by single-dose administration of either 1) placebo, 2) the SGLT2i empagliflozin (25 mg), 3) the glucagon receptor antagonist LY2409021 (300 mg), or 4) the combination empagliflozin + LY2409021. Empagliflozin and LY2409021 individually lowered fasting PG compared with placebo, and the combination further decreased fasting PG. Previous findings of increased glucagon concentrations and EGP during acute administration of SGLT2i were not replicated in this study. Empagliflozin reduced postprandial PG through increased urinary glucose excretion. LY2409021 reduced EGP significantly but gave rise to a paradoxical increase in postprandial PG excursion, which was annulled by empagliflozin during their combination (empagliflozin + LY2409021). In conclusion, our findings do not support that an SGLT2i-induced glucagonotropic effect is of importance for the glucose-lowering property of SGLT2 inhibition.

Evaluating the potential role of tryptophan in calf milk replacers to facilitate weaning

Tryptophan is a precursor of serotonin, a neurotransmitter that participates in the control of the affective state of an animal. We hypothesized that Trp supplementation could help dairy calves to cope with weaning stress. Twenty-seven Holstein male calves (48 ± 0.8 d old; 82 ± 2.6 kg of body weight) were used to evaluate the effects of Trp supplementation at a rate of 4.5 g/d via milk replacer (MR) on performance and behavioral parameters around weaning. All calves received the same feeding program (6 L/d at 15% dry matter from d 1 to 7, 4 L/d at 15% dry matter from d 8 to 14, and 2 L/d at 15% dry matter in one feeding until d 21 of study) and were completely weaned 22 d after the beginning of the study (around 70 d of life). Calves were fed a starter feed (19.3% crude protein and 16.2% neutral detergent fiber, on a dry matter basis) and chopped straw ad libitum. Animals were weighed weekly, dry matter intakes were recorded daily, lying behavior was recorded using accelerometers throughout the study, and scan sampling was performed twice a week, 1 h after the morning feeding, to record behavioral activity (nonnutritive oral behaviors, suckling a neighbor calf, standing, resting, rumination, vocalizations, eating, and drinking). Tryptophan supplementation did not affect calf performance or concentrate and MR intake, but straw intake tended to be greater in nonsupplemented compared with Trp-supplemented calves (153 vs. 129 ± 9.0 g/d, respectively). Lying time, lying bouts, and lying duration decreased when changes in the MR feeding program occurred, independent of treatment. Similarly, differences in behavioral observations occurred along days of study, with no effect of Trp supplementation. The main changes observed in calf behavior were an increase in vocalizations and standing time 1 h after the morning feeding at weaning, but again these changes were independent of treatment. Parameters measured in serum and plasma indicated an increase in Trp, kynurenine, and the kynurenine/Trp ratio after feeding in the Trp calves. A tendency for lower plasma glucose concentration after feeding was observed in the Trp group. No changes in stress markers such as cortisol and haptoglobin in serum were detected. In conclusion, supplementing 4.5 g/d of Trp via MR between 48 and 62 d of life had no effect on performance or behavior in calves around weaning.

Glucose Homeostasis and the Neonatal Brain: A Sweet Relationship.

Glucose is the primary substrate for energy metabolism in the brain and although the brain is dependent on a constant glucose supply for normal function, both local energy stores and the supply of alternate substrates are limited. In utero, the placenta provides a continuous supply of glucose to the fetus while transition to extrauterine life marks an abrupt change in substrate delivery and a major change in glucose metabolism where insufficiencies and disruptions can occur. Hypoglycemia is one of the most common biochemical disturbances in the neonatal period, affecting a wide range of neonates. Prolonged or persistent low plasma glucose concentrations can lead to neonatal brain injury and abnormal neurological outcomes. This article discusses fetal and neonatal metabolic adaptation, the physiology of glucose homeostasis, hypoglycemic brain injury (HBI), and neurodevelopmental long-term outcomes.

ApoA-1 improves glucose tolerance by increasing glucose uptake into heart and skeletal muscle independently of AMPKα2

ObjectiveAcute administration of the main protein component of high-density lipoprotein, apolipoprotein A-I (ApoA-1), improves glucose uptake in skeletal muscle. The molecular mechanisms mediating this are not known, but in muscle cell cultures, ApoA-1 failed to increase glucose uptake when infected with a dominant-negative AMP-activated protein kinase (AMPK) virus. We therefore investigated whether AMPK is necessary for ApoA-1-stimulated glucose uptake in intact heart and skeletal muscle in vivo. MethodsThe effect of injection with recombinant human ApoA-1 (rApoA-1) on glucose tolerance, glucose-stimulated insulin secretion, and glucose uptake into skeletal and heart muscle with and without block of insulin secretion by injection of epinephrine (0.1 mg/kg) and propranolol (5 mg/kg), were investigated in 8 weeks high-fat diet-fed (60E%) wild-type and AMPKα2 kinase-dead mice in the overnight-fasted state. In addition, the effect of rApoA-1 on glucose uptake in isolated skeletal muscle ex vivo was studied. ResultsrApoA-1 lowered plasma glucose concentration by 1.7 mmol/l within 3 h (6.1 vs 4.4 mmol/l; p < 0.001). Three hours after rApoA-1 injection, glucose tolerance during a 40-min glucose tolerance test (GTT) was improved compared to control (area under the curve (AUC) reduced by 45%, p < 0.001). This was accompanied by an increased glucose clearance into skeletal (+110%; p < 0.001) and heart muscle (+100%; p < 0.001) and an increase in glucose-stimulated insulin secretion 20 min after glucose injection (+180%; p < 0.001). When insulin secretion was blocked during a GTT, rApoA-1 still enhanced glucose tolerance (AUC lowered by 20% compared to control; p < 0.001) and increased glucose clearance into skeletal (+50%; p < 0.05) and heart muscle (+270%; p < 0.001). These improvements occurred to a similar extent in both wild-type and AMPKα2 kinase-dead mice and thus independently of AMPKα2 activity in skeletal- and heart muscle. Interestingly, rApoA-1 failed to increase glucose uptake in isolated skeletal muscles ex vivo. ConclusionsIn conclusion, ApoA-1 stimulates in vivo glucose disposal into skeletal and heart muscle independently of AMPKα2. The observation that ApoA-1 fails to increase glucose uptake in isolated muscle ex vivo suggests that additional systemic effects are required.

Differential glucose bioaccessibility from native and modified taro-starches in the absence or presence of beet juice

ABSTRACT The speed of starch-digestion defines peak blood-glucose concentrations. Slow digestion is beneficial for diabetic individuals. To investigate the effects on blood-glucose it is important to be able to predict the amount of digestible starch. Therefore, the aim of this study was to compare the digestibility of different starches in a validated in-vitro model of the upper gastrointestinal (GI) tract. Digestion was performed in the TNO dynamic, computer-controlled in-vitro model of the upper GI-tract (TIM-1). Release of glucose was measured over time. Products tested were taro-flour, native-, and modified taro-starch. The latter two were also tested with beet-juice adsorbed. These were compared to wheat-flour and a glucose-solution. Modified taro-starch showed a similar glucose-bioaccessibility as wheat-flour (81–83%), while the other products tested had a lower bioaccessibility (60–75%). Adsorption of beet-juice affected digestibility of the modified taro-starch, but not the native-starch. Taro-based products can be used to lower plasma glucose concentrations in diabetic individuals.