The effects of either low (25 pnollmin) or high (235 pnol/min) infusion of NH&l into the mesenteric vein for 5 d were determined on 0, consumption plus urea and amino acid transfers across the portaldrained viscera (PDV) and liver of young sheep. Kinetic transfers were followed by use of l5NH4C1 for 10 h on the fifth day with simultaneous infusion of [l-'3C]leucine to monitor amino acid oxidation.Neither PDV nor liver blood flow were affected by the additional NH, loading, although at the higher rate there was a trend for increased liver 0, consumption. N&-N extraction by the liver accounted for 64-70 % of urea-N synthesis and at the lower infusion rate the additional N required could be more than accounted for by hepatic removal of free amino acids. At the higher rate of NH, administration additional sources of N were apparently required to account fully for urea synthesis. Protein synthesis rates in the PDV and liver were unaffected by NH3 infusion but both whole-body (P < 0.05) and splanchnic tissue leucine oxidation were elevated at the higher rate of administration. Substantial synthesis of [15wglutamine occurred across the liver, particularly with the greater NH, supply, and enrichments exceeded considerably those of glutamate. The [15N]urea synthesized was predominantly as the single labelled, i.e. [14N15N], species. These various kinetic data are compatible with the action of ovine hepatic glutamate dehydrogenase (EC1.4.1.2) in periportal hepatocytes in the direction favouring glutamate deamhation. Glutamate synthesis and uptake is probably confined to the perivenous cells which do not synthesize urea. The implications of NH, detoxification to the energy and N metabolism of the ruminant are discussed.

1. The rate of blood flow in the portal and hepatic veins, and the net exchange across the gut and liver of volatile fatty acids (VFA), glucose, lactate, pyruvate, amino acids, ketone bodies, glycerol, non-esterified fatty acids (NEFA) and oxygen, were measured in lactating and non-lactating cows (a) in the normal, fed state and (b) before, during and after 6 d of fasting.2. Blood flow rate through the liver was 52% higher in normal, fed, lactating cows as compared with non-lactating cows, and was decreased by fasting in both groups of cows. Portal blood flow rate increased with an increase in metabolizable energy (ME) intake.3. Lactating, as compared with non-lactating, cows exhibited lower arterial concentrations of glucose and lactate, higher net portal outputs of VFA and ketone bodies, a higher net hepatic output of glucose, and higher net hepatic uptakes of propionate and lactate. The splanchnic outputs of acetate, glucose and hydroxybutyrate were all apparently greater in the lactating cows.4. Fasting caused a rapid decrease in the blood concentrations of the VFA and an increase in those of glycerol and NEFA. The portal, i.e. gut, outputs of VFA, lactate, ketone bodies, alanine and (serine+ threonine), and the portal uptake of 0,, were all decreased by fasting. Fasting for 6 h also decreased the hepatic output of glucose and acetate by 77 and 95% respectively, increased the hepatic uptake of pyruvate, glycerol and NEFA, and doubled hepatic ketone-body output. The splanchnic output of acetate and glucose and the splanchnic uptake of 0, were also decreased by fasting. 5.The net portal outputs of VFA, lactate and hydroxybutyrate, and the net hepatic output of glucose, were all correlated with ME intake in fed and fasted cows. Hepatic glucose output was also correlated with milk yield. 6. The net hepatic uptake of gluconeogenic precursors measured in this study could account for net hepatic glucose output in the fasted cows, but not in the fed cows. The net hepatic uptake of the ketogenic precursors butyrate and NEFA was sufficient to account for the hepatic output of ketone bodies in both fed and fasted cows, but it is unlikely that the hepatic uptake of ketogenic precursors could also account for the observed hepatic output of acetate.The gut and liver of the dairy cow can be considered to operate together as a functional unit, termed the splanchnic bed, that supplies nutrients to the remainder of the body. During lactation the splanchnic bed plays a major role in supplying precursors required for milk synthesis. Therefore, changes in metabolite flux across the splanchnic bed will be expected to have major effects on milk synthesis and on the metabolic status of the animal. Alterations in splanchnic metabolism could arise as a result of variation in feed intake or of metabolic events associated with milk production.In the present study the effects of differences in feed intake were monitored by comparing fed and fasted cows, while the effects of differences in productive demand were monitored by comparing la...

SUMMARY1. This study examines the effect of chronic cold exposure during pregnancy, induced by winter shearing twin-bearing ewes 4 weeks before predicted lambing date, on 02 consumption and CO2 production during non-rapid-eye-movement (REM) sleep in lambs maintained for at least 1 h at warm (28-18 'C) and cold (14-5 'C) ambient temperatures at 1, 4, 14 and 30 days of age. This was combined with measurement of the thermogenic activity (GDP binding to uncoupling protein in mitochondrial preparations) of perirenal adipose tissue from lambs immediately after birth and at 33 days of age.2. Lambs born from shorn (cold-exposed) ewes were 15% heavier (P < 0-01) and possessed 21 % (P < 0-01) more perirenal adipose tissue that contained 40% more protein and mitochondrial protein than unshorn (P < 0-05) controls. Total GDP binding in perirenal adipose tissue was 40 % greater (P < 0'05) in lambs born from shorn ewes but there was no difference in lipid content of this tissue between the two groups.3. At 1 day of age, lambs born from shorn ewes exhibited a 16 % higher (P < 0 05) rate of 02 consumption (per kilogram bodyweight) at the warm temperature and a 40 % greater metabolic response to the cold ambient temperature. All lambs born from shorn ewes responded to cold exposure without shivering (i.e. via non-shivering thermogenesis) whilst shivering was measured in four out of seven lambs in the unshorn group. These differences had disappeared by 4 days of age as a result of a 25% increased (P < 0-01) rate of 02 consumption in the warm in lambs born from unshorn ewes and a 20 % decrease (P < 0 05) in the response to the cold in lambs from shorn ewes. Shivering during cold exposure was measured in six out of nine lambs born from shorn ewes indicating a rapid alteration in thermoregulatory responses to cold during the first few days of life.4. The levels of GDP binding and mitochondrial protein in perirenal adipose tissue fell by one-third in both groups of lambs during the first 33 days of life whereas lipid content either increased or was unchanged. This indicated that brown adipose tissue (BAT) was developing the characteristics of white adipose tissue. In lambs aged 33 days that were born from shorn ewes, perirenal adipose tissue weighed 88 % more MS 9883 M. E SYMONDS AND OTHERS (P < 0 01), contained more (P < 0 05) protein and lipid, and the level of total GDP binding to mitochondrial protein was 100 % greater than in lambs born from unshorn ewes. There were no differences at this age between the two groups of lambs in metabolic rate but four out of eight lambs born from shorn ewes exhibited shivering responses to a cold ambient temperature compared with seven out of eight in the unshorn group.5. It is concluded that maternal cold exposure during late pregnancy stimulates fetal growth and the thermogenic activity of BAT in the neonatal lamb. At 1 day of age this alternation in BAT was associated with an increased metabolic response to cold achieved entirely via non-shivering thermogenesis while longer term consequences...

PurposeThe purpose of this study was to determine the impact of diabetes self-management education (DSME) in improving processes and outcomes of diabetes care as measured by a five component diabetes bundle and HbA1c, in individuals with type 2 diabetes mellitus (T2DM).MethodsA retrospective analysis was performed for adult T2DM patients who received DSME training in 2011–2012 from an accredited American Diabetes Association center at Intermountain Healthcare (IH) and had an HbA1c measurement within the prior 3 months and 2–6 months after completing their first DSME visit. Control patients were selected from the same clinics as case-patients using random number generator to achieve a 1 to 4 ratio. Case and control patients were included if 1) pre-education HbA1c was between 6.0%–14.0%; 2) their main provider was a primary care physician; 3) they met the national Healthcare Effectiveness Data and Information Set criteria for inclusion in the IH diabetes registry. The IH diabetes bundle includes retinal eye exam, nephropathy screening or prescription of angiotensin converting enzyme or angiotensin receptor blocker; blood pressure <140/90 mmHg, LDL <100 mg/dL, HbA1c <8.0%.ResultsDSME patients had a significant difference in achievement of the five element IH diabetes bundle and in HbA1c % compared to those without DSME. After adjusting for possible confounders in a multivariate logistic regression model, DSME patients had a 1.5 fold difference in improvement in their diabetes bundle and almost a 3 fold decline in HbA1c compared to the control group.ConclusionStandardized DSME taught within an IH American Diabetes Association center is strongly associated with a substantial improvement in patients meeting all five elements of a diabetes bundle and a decline in HbA1c beyond usual care. Given the low operating cost of the DSME program, these results strongly support the value adding benefit of this program in treating T2DM patients.

cAMP-dependent protein kinase induction of PPAR␥ coactivator-1␣ (PGC-1␣) and uncoupling protein 1 (UCP1) expression is an essential step in the commitment of preadipocytes to the brown adipose tissue (BAT) lineage. We studied the molecular mechanisms responsible for differential expression of PGC-1␣ in HIB1B (BAT) and 3T3-L1 white adipose tissue (WAT) precursor cell lines. In HIB1B cells PGC-1␣ and UCP1 expression is cAMP-inducible, but in 3T3-L1 cells, expression is reduced and is cAMP-insensitive. A proximal 264-bp PGC-1␣ reporter construct was cAMP-inducible only in HIB1B cells and was suppressed by site-directed mutagenesis of the proximal cAMP response element (CRE). In electrophoretic mobility shift assays, the transcription factors CREB and C/EBP␤, but not C/EBP␣ and C/EBP␦, bound to the CRE on the PGC-1␣ promoter region in HIB1B and 3T3-L1 cells. Chromatin immunoprecipitation studies demonstrated that C/EBP␤ and CREB bound to the CRE region in HIB1B and 3T3-L1 cell lysates. C/EBP␤ expression was induced by cAMP only in HIB1B cells, and overexpression of C/EBP␤ rescued cAMP-inducible PGC-1␣ and UCP1 expression in 3T3-L1 cells. These data demonstrate that differentiation of preadipocytes toward the BAT rather than the WAT phenotype is controlled in part by the action of C/EBP␤ on the CRE in PGC-1␣ proximal promoter.

1. Circulating concentrations of glucose, propionate, lactate and pyruvate, and net exchange of these compounds across the liver and gut, were measured in lactating and non-lactating dairy cows (a) in the normal fed state, (b) before, during and after intravenous infusion of an aqueous solution of glucose, propionate or lactate (lactating cows only) in fed animals, and (c) before and during 6 days of food deprivation. 2. In the normal fed state, gut output of propionate, hepatic output of glucose and hepatic uptake of lactate were all higher in the lactating group. There was a net uptake of pyruvate across the liver in the lactating cows and a net output in the non-lactating cows. In the lactating cows there was a net uptake of lactate and pyruvate by the splanchnic bed (i.e. gut and liver combined). 3. In the lactating cows, the glucose and propionate infusions had the following effects: decrease in net hepatic uptake of lactate; a switch in pyruvate exchange across the liver from uptake to output; suppression of uptake of lactate and pyruvate by the splanchnic bed; increase in the magnitude of the liver (propionate uptake)/(glucose output) ratio. Lactate infusion did not affect hepatic propionate uptake. 4. Food deprivation increased hepatic extraction of lactate and pyruvate and decreased the liver (propionate uptake)/(glucose output) ratio in both groups. 5. It is concluded that mechanisms exist to ensure an inverse relationship between the availability to the cow of glucose or propionate and utilization by the splanchnic bed of endogenously derived lactate and pyruvate.

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We examined the effect of maternal chronic cold exposure, induced by winter-shearing ewes 4 weeks before their predicted lambing date, on brown adipose tissue (BAT) and liver development in lambs. Fetuses were sampled from under-fed (60% of energy requirements for maintenance and pregnancy of an unshorn ewe) shorn or unshorn ewes at 126,140 and 145 d of gestation. Lambs were sampled from ewes within 2 h of birth. Throughout gestation fetal body, BAT and liver weights were similar in shorn and unshorn groups. The level of GDP binding to mitochondrial uncoupling protein remained low throughout gestation, but increased dramatically after birth. Lambs born to shorn ewes possesd more mitochondrial protein and exhibited a significantly higher total thermogenic activity in BAT. Type I iodothyronine 5 deiodinas(EC 3.8.1.4) activity in BAT peaked at birth, as did hepatic iodothyronine Sdeiodinase activity and was significantly greater in lambs born to under-fed shorn ewes, which exhibited a higher plasma triiodothyronine concentration. Chronic maternal adaptations to prolonged cold exposure appear to enable pregnant ewes to compensate for the negative effects of under-feeding on fetal growth and development