Glucose metabolism in pregnant sheep when placental growth is restricted

1989 ◽  
Vol 257 (2) ◽  
pp. R350-R357 ◽  
Author(s):  
J. A. Owens ◽  
J. Falconer ◽  
J. S. Robinson
Keyword(s):  
Glucose Metabolism ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Gravid Uterus ◽  
Glucose Turnover ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Pregnant Sheep ◽  
Endogenous Glucose

The effect of restricting placental growth on glucose metabolism in pregnant sheep in late gestation was determined by primed constant infusions of D-[U-14C]- and D-[2-3H]glucose and antipyrine into fetuses of six control sheep and six sheep from which endometrial caruncles had been removed before pregnancy (caruncle sheep). In the latter, placental and fetal weights were reduced, as was the concentration of glucose in fetal arterial blood. Fetal glucose turnover in caruncle sheep was only 52-59% of that in controls, largely because of lower umbilical loss of glucose back to the placenta (38-39% of control) and lower fetal glucose utilization (61-74% of control). However, fetal glucose utilization on a weight-specific basis was similar in control and caruncle sheep. Significant endogenous glucose production occurred in control and caruncle fetal sheep. Maternal glucose production and partition of glucose between the gravid uterus and other maternal tissues were similar in control and caruncle sheep. In conclusion, when placental and fetal growth are restricted, fetal glucose utilization is maintained by reduced loss of glucose back to the placenta and mother and by maintaining endogenous glucose production.

scholarly journals Insulin action and glucose metabolism in sheep fed on dried-grass or ground, maize-based diets

1985 ◽  
Vol 54 (2) ◽  
pp. 459-471 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong
Keyword(s):  
Glucose Metabolism ◽  
Insulin Action ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Metabolic Clearance ◽  
Endogenous Glucose

1. The effect of an exogenous supply of glucose, provided by the digestion of maize starch in the small intestine, on endogenous glucose metabolism and insulin action was studied in sheep using the euglycaemic insulin clamp procedure.2. Insulin was infused intravenously at rates of 0.2, 0.5, 1.0 and 6.0 mU/min per kg live weight for four consecutive periods in each of four sheep fed on dried-grass and maize-based diets. Glucose was also infused intravenously at a variable rate, sufficient to maintain the plasma glucose concentration at basal levels. Whole-body rates of glucose metabolism were determined using a continuous infusion of [6-3H]glucose.3. From the resultinginsulin dose-response curves, it was observed that, when the sheep were fed on the dried-grass diet, the responsiveness of glucose metabolism to insulin was less than that reported for non-ruminants.4. When fed the maize-based diet, the glucose metabolic clearance rates (MCR) observed during insulin infusions were significantly greater (P < 0.05) than those observed for the dried-grass diet. However, after correcting for the non-insulin-mediated glucose disposal, differences between diets were not significant.5. The sensitivity of glucose utilization to insulin was not affected by diet. The plasma insulin concentrations causing half-maximal insulin-mediated glucose MCR were 103 (SE 21) and 85 (SE 11) mU/l for the dried-grass and maize-based diets respectively.6. The sensitivity of endogenous glucose production to insulin was also unaffected by diet. The plasma insulin concentrations resulting in the suppression of endogenous glucose production to half the basal level were 80 (SE 26) and 89 (SE 29) mU/l for the dried-grass and maize-based diets respectively.7. It is concluded that the observed increase in glucose utilization on the maize-based diet was due partly to a slight change in responsiveness to insulin and also partly to a change in the rate of non-insulin-mediated glucose disposal.

Insulin regulation of renal glucose metabolism in humans

1999 ◽  
Vol 276 (1) ◽  
pp. E78-E84 ◽  
Author(s):  
Eugenio Cersosimo ◽  
Peter Garlick ◽  
John Ferretti
Keyword(s):  
Glucose Metabolism ◽  
Insulin Infusion ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Saline Infusion ◽  
Saline Control ◽  
Control Group ◽  
Renal Gluconeogenesis ◽  
Endogenous Glucose

Eighteen healthy subjects had arterialized hand and renal veins catheterized after an overnight fast. Systemic and renal glucose and glycerol kinetics were measured with [6,6-2H2]glucose and [2-13C]glycerol before and after 180-min peripheral infusions of insulin at 0.125 (LO) or 0.25 (HI) mU ⋅ kg−1 ⋅ min−1with variable [6,6-2H2]dextrose or saline (control). Renal plasma flow was determined by plasma p-aminohippurate clearance. Arterial insulin increased from 37 ± 8 to 53 ± 5 (LO) and to 102 ± 10 pM (HI, P < 0.01) but not in control (35 ± 8 pM). Arterial glucose did not change and averaged 5.2 ± 0.1 (control), 4.7 ± 0.2 (LO), and 5.1 ± 0.2 (HI) μmol/ml; renal vein glucose decreased from 4.8 ± 0.2 to 4.5 ± 0.2 μmol/ml (LO) and from 5.3 ± 0.2 to 4.9 ± 0.1 μmol/ml (HI) with insulin but not saline infusion (5.3 ± 0.1 μmol/ml). Endogenous glucose production decreased from 9.9 ± 0.7 to 6.9 ± 0.5 (LO) and to 5.7 ± 0.5 (HI) μmol ⋅ kg−1 ⋅ min−1; renal glucose production decreased from 2.5 ± 0.6 to 1.5 ± 0.5 (LO) and to 1.2 ± 0.6 (HI) μmol ⋅ kg−1 ⋅ min−1, whereas renal glucose utilization increased from 1.5 ± 0.6 to 2.6 ± 0.7 (LO) and to 2.9 ± 0.7 (HI) μmol ⋅ kg−1 ⋅ min−1after insulin infusion (all P < 0.05 vs. baseline). Neither endogenous glucose production (10.0 ± 0.4), renal glucose production (1.1 ± 0.4), nor renal glucose utilization (0.8 ± 0.4) changed in the control group. During insulin infusion, systemic gluconeogenesis from glycerol decreased from 0.67 ± 0.05 to 0.18 ± 0.02 (LO) and from 0.60 ± 0.04 to 0.20 ± 0.02 (HI) μmol ⋅ kg−1 ⋅ min−1( P < 0.01), and renal gluconeogenesis from glycerol decreased from 0.10 ± 0.02 to 0.02 ± 0.02 (LO) and from 0.15 ± 0.03 to 0.09 ± 0.03 (HI) μmol ⋅ kg−1 ⋅ min−1( P < 0.05). In contrast, during saline infusion, systemic (0.66 ± 0.03 vs. 0.82 ± 0.05 μmol ⋅ kg−1 ⋅ min−1) and renal gluconeogenesis from glycerol (0.11 ± 0.02 vs. 0.41 ± 0.04 μmol ⋅ kg−1 ⋅ min−1) increased ( P < 0.05 vs. baseline). We conclude that glucose production and utilization by the kidney are important insulin-responsive components of glucose metabolism in humans.

scholarly journals Sex-specific programming of adult insulin resistance in guinea pigs by variable perinatal growth induced by spontaneous variation in litter size

2019 ◽  
Vol 316 (4) ◽  
pp. R352-R361
Author(s):  
Dane M. Horton ◽  
David A. Saint ◽  
Kathryn L. Gatford ◽  
Karen L. Kind ◽  
Julie A. Owens
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Guinea Pigs ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Catch Up ◽  
Endogenous Glucose

Intrauterine growth restriction (IUGR) and subsequent neonatal catch-up growth are implicated in programming of insulin resistance later in life. Spontaneous IUGR in the guinea pig, due to natural variation in litter size, produces offspring with asymmetric IUGR and neonatal catch-up growth. We hypothesized that spontaneous IUGR and/or accelerated neonatal growth would impair insulin sensitivity in adult guinea pigs. Insulin sensitivity of glucose metabolism was determined by hyperinsulinemic-euglycemic clamp (HEC) in 38 (21 male, 17 female) young adult guinea pigs from litters of two-to-four pups. A subset (10 male, 8 female) were infused with d-[3-3H]glucose before and during the HEC to determine rates of basal and insulin-stimulated glucose utilization, storage, glycolysis, and endogenous glucose production. n males, the insulin sensitivity of whole body glucose uptake ( r = 0.657, P = 0.002) and glucose utilization ( r = 0.884, P = 0.004) correlated positively and independently with birth weight, but not with neonatal fractional growth rate (FGR10–28). In females, the insulin sensitivity of whole body and partitioned glucose metabolism was not related to birth weight, but that of endogenous glucose production correlated negatively and independently with FGR10–28 ( r = −0.815, P = 0.025). Thus, perinatal growth programs insulin sensitivity of glucose metabolism in the young adult guinea pig and in a sex-specific manner; impaired insulin sensitivity, including glucose utilization, occurs after IUGR in males and impaired hepatic insulin sensitivity after rapid neonatal growth in females.

scholarly journals Absorption and metabolism of glucose by the mesenteric-drained viscera of sheep fed on dried-grass or ground, maize-based diets

1985 ◽  
Vol 54 (2) ◽  
pp. 449-458 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong
Keyword(s):  
Small Intestine ◽  
Turnover Rate ◽  
Glucose Utilization ◽  
Venous Blood ◽  
Glucose Production ◽  
Glucose Absorption ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Glucose Turnover ◽  
Total Glucose

1. Sheep fitted with re-entrant canulas in the proximal duodenum and terminal ileum were used to determine the amount of α-glucoside entering, and apparently disappearing from, the small intestine when either dried-grass or ground maize-based diets were fed. The fate of any α-glucoside entering the small intestine was studied by comparing the net disappearance of such a-glucoside from the small intestine with the absorption of glucose into the mesenteric venous blood.2. Glucose absorption from the small intestine was measured in sheep equipped with catheters in the mesenteric vein and carotid artery. A continuous infusion of [6-3H]glucose was used to determine glucose utilization by the mesenteric-drained viscera and the whole-body glucose turnover rate (GTR).3. The amounts of α-glucoside entering the small intestine when the dried-grass and maize-based diets were given were 13.9 (SE 1.5) and 95.4 (SE 16.2) g/24 h respectively; apparent digestibilities of such α-glucoside in the small intestine were 60 and 90% respectively.4. The net absorption of glucose into the mesenteric venous blood was —2.03 (SE 1.20) and 19.28 (SE 0.75) mmol/h for the dried-grass and maize-based diets respectively. Similarly, total glucose absorption amounted to 1.52 (SE 1.35) and 23.33 (SE 1.86) mmol/h (equivalent to 7 and 101 g/24 h respectively). These values represented 83 and 11 1% of the a-glucoside apparently disappearing from the small intestine, determined using the re-entrant cannulated sheep.5. Total glucose absorption represented 8 and 61% of the whole-body GTR for the dried-grass and maize-based diets respectively. Endogenous glucose production was significantly lower when the sheep were fed on the maize-based diet compared with the dried-grass diet.6. The mesenteric-drained viscera metabolized a small amount of glucose, equivalent to 234 and 17% of the total glucose absorbed for the dried-grass and maize-based diets respectively.7. It is concluded that a large proportion of the starch entering the small intestine of sheep given a maize-based diet is digested and absorbed as glucose, and thus contributes to the whole-body GTR.

Insulin sensitivity of glucose and fat metabolism in severe sepsis

2000 ◽  
Vol 99 (4) ◽  
pp. 321-328 ◽  
Author(s):  
Cécile CHAMBRIER ◽  
Martine LAVILLE ◽  
Khalid RHZIOUAL BERRADA ◽  
Michelle ODEON ◽  
Paul BOULÉTREAU ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Insulin Infusion ◽  
Glucose Utilization ◽  
Fat Metabolism ◽  
Glucose Production ◽  
Normal Subjects ◽  
Endogenous Glucose Production ◽  
Exogenous Insulin ◽  
Control Subjects ◽  
Endogenous Glucose

In order to quantify the changes in insulin sensitivity, particularly of endogenous glucose production and fat metabolism, in patients with severe sepsis, a prospective study was conducted in five normal subjects and in five patients with severe sepsis hospitalized in an intensive care unit. The responses of endogenous glucose production, glucose utilization, plasma fatty acids and ketone body concentrations to progressive increase in plasma insulin levels (exogenous insulin infusion rates of 0, 0.5, 1 and 2 m-unitsċmin-1ċkg-1) were measured using the isoglycaemic clamp technique. Total glucose turnover was determined with D-[6,6-2H2]glucose. In each group, plasma glucose was maintained at basal levels (control subjects, 4.32±0.22 mmolċl-1; patients with sepsis, 7.10±2.29 mmolċl-1; P < 0.05). Plasma insulin concentrations were comparable in the two groups at an insulin infusion rate of 0.4 m-unitċmin-1ċkg-1 for controls and 0.5 m-unitċmin-1ċkg-1 for patients with sepsis, but differed following infusion at 2 m-unitċmin-1ċkg-1 (control subjects, 102±13.4 m-unitsċl-1; patients with sepsis, 124.8±19.7 m-unitsċl-1; P < 0.05). Endogenous glucose production was completely suppressed in control subjects by the first insulin infusion (0.4 m-unitċmin-1ċkg-1), but was only suppressed during infusion at 1 m-unitċmin-1ċkg-1 insulin in patients with sepsis. The glucose utilization rate increased significantly with exogenous insulin infusion in control subjects, but did not increase in patients with sepsis. Plasma non-esterified (free) fatty acid and ketone body levels were significantly decreased in both groups by the infusion of exogenous insulin, but the sensitivity of lipolysis was impaired in patients with sepsis. In conclusion, sepsis impaired to a varying extent the action of insulin on endogenous glucose production, glucose utilization, lipolysis and ketogenesis. Whole-body glucose uptake was the most affected, with a total lack of response to the elevated insulin levels obtained in this study. Suppression of endogenous glucose production and lipolysis could only be achieved with higher doses of insulin than those required in normal subjects.

scholarly journals Influence of dietary fat on postprandial glucose metabolism (exogenous and endogenous) using intrinsically 13C-enriched durum wheat

2001 ◽  
Vol 86 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Sylvie Normand ◽  
Yadh Khalfallah ◽  
Corinne Louche-Pelissier ◽  
Christiane Pachiaudi ◽  
Jean-Michel Antoine ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Glucose Production ◽  
Postprandial Glucose ◽  
Endogenous Glucose Production ◽  
Glucose Turnover ◽  
Exogenous Glucose ◽  
Esterified Fatty Acids ◽  
Secondary Recovery ◽  
Total Glucose

The present study evaluates the influence of different amounts of fat added to starch on postprandial glucose metabolism (exogenous and endogenous). Nine women (24 (SE 2) YEARS OLD, BMI 20·4 (se 0·7) kg/m2) ingested 1 week apart 75 g glucose equivalent of 13C-labelled starch in the form of pasta without (low fat; LF) or with 15 (medium fat; MF) or 40 (high fat; HF) g sunflower oil. During the 7 h following meal consumption, plasma glucose, non-esterified fatty acids, triacylglycerols (TG) and insulin concentrations, and endogenous (using [6,6-2H2]glucose) and exogenous glucose turnover were determined. With MF and HF meals, a lower postprandial glucose peak was observed, but with a secondary recovery. A decrease in exogenous glucose appearance explained lower glycaemia in HF. At 4 h after the HF meal the insulin, insulin:glucose and postprandial blood TG were higher than those measured after the LF and MF meals. Despite higher insulinaemia, total glucose disappearance was similar and endogenous glucose production was suppressed less than after the LF and MF meals, suggesting insulin resistance. Thus, the addition of a large amount of fat appears to be unfavourable to glucose metabolism because it leads to a feature of insulin resistance. On the contrary, the MF meal did not have these adverse effects, but it was able to decrease the initial glycaemic peak.

scholarly journals Effects of maternal undernutrition and exercise on glucose kinetics in fetal sheep

1990 ◽  
Vol 64 (2) ◽  
pp. 463-472 ◽  
Author(s):  
B. J. Leury ◽  
K. D. Chandler ◽  
A. R. Bird ◽  
A. W. Bell
Keyword(s):  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Glucose Disposal ◽  
Utilization Rate ◽  
Glucose Kinetics ◽  
Arterial Blood ◽  
Net Uptake ◽  
Endogenous Glucose ◽  
Total Glucose ◽  
Glucose Disposal Rate

Fetal glucose kinetics were measured using a combination of isotope-dilution and Fick-principle methodology in single-pregnant ewes which were either well-fed throughout, or fed at 0.3–0.4 predicted energy requirement for 7–21 d during late pregnancy. All ewes were studied while standing at rest and then while walking on a treadmill at 0.7 m/s on a 10° slope for 60 min. Underfed ewes suffered major decreases in fetal total disposal rate, fetal-placental transfer and umbilical net uptake of glucose, each of which were significantly related to declines in maternal and fetal blood glucose concentrations respectively. In well-fed ewes, fetal endogenous glucose production was negligible, as indicated by the similarity between fetal utilization rate (total glucose disposal rate minus placental uptake of fetal glucose) and umbilical net uptake of glucose, and by nearly identical fetal and maternal arterial blood specific radioactivities of maternally infused D-[2-3H]glucose. By contrast, in underfed ewes, fetal utilization rate greatly exceeded umbilical net uptake of glucose, and the fetal:maternal [3H]glucose specific activity ratio declined significantly, suggesting induction of a substantial rate of fetal endogenous glucogenesis. Exercise caused increases in fetal total glucose disposal rate and glycaemia in fed and underfed ewes. In underfed ewes only, this was accompanied by increased placental uptake of fetal glucose and umbilical net glucose uptake, unchanged fetal glucose utilization and decreased fetal endogenous glucose production. It is concluded that fetal gluconeogenesis makes a major contribution to fetal glucose requirements in undernourished ewes. Increased maternal supply of fetal glucose during exercise substitutes for rather than adds to fetal endogenous glucogenesis.

Use of a novel triple-tracer approach to assess postprandial glucose metabolism

2003 ◽  
Vol 284 (1) ◽  
pp. E55-E69 ◽  
Author(s):  
Rita Basu ◽  
Barbara Di Camillo ◽  
Gianna Toffolo ◽  
Ananda Basu ◽  
Pankaj Shah ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Production ◽  
Compartment Model ◽  
Postprandial Glucose ◽  
Endogenous Glucose Production ◽  
Two Compartment Model ◽  
Nonsteady State ◽  
Model Independent ◽  
Endogenous Glucose ◽  
Dual Tracer

Numerous studies have used the dual-tracer method to assess postprandial glucose metabolism. The present experiments were undertaken to determine whether the marked tracer nonsteady state that occurs with the dual-tracer approach after food ingestion introduces error when it is used to simultaneously measure both meal glucose appearance (Ra meal) and endogenous glucose production (EGP). To do so, a novel triple-tracer approach was designed: 12 subjects ingested a mixed meal containing [1-13C]glucose while [6-3H]glucose and [6,6-2H2]glucose were infused intravenously in patterns that minimized the change in the plasma ratios of [6-3H]glucose to [1-13C]glucose and of [6,6-2H2]glucose to endogenous glucose, respectively. Ra meal and EGP measured with this approach were essentially model independent, since non-steady-state error was minimized by the protocol. Initial splanchnic glucose extraction (ISE) was 12.9% ± 3.4%, and suppression of EGP (EGPS) was 40.3% ± 4.1%. In contrast, when calculated with the dual-tracer one-compartment model, ISE was higher ( P < 0.05) and EGPS was lower ( P < 0.005) than observed with the triple-tracer approach. These errors could only be prevented by using time-varying volumes different for Ra meal and EGP. Analysis of the dual-tracer data with a two-compartment model reduced but did not totally avoid the problems associated with marked postprandial changes in the tracer-to-tracee ratios. We conclude that results from previous studies that have used the dual-tracer one-compartment model to measure postprandial carbohydrate metabolism need to be reevaluated and that the triple-tracer technique may provide a useful approach for doing so.

Impact of portal glucose delivery on glucose metabolism in conscious, unrestrained mice

2006 ◽  
Vol 291 (6) ◽  
pp. E1206-E1211 ◽  
Author(s):  
Fu-Yu Chueh ◽  
Carlo Malabanan ◽  
Owen P. McGuinness
Keyword(s):  
Glycogen Synthesis ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Glucose Turnover ◽  
Hepatic Glycogen ◽  
Similar Response ◽  
Indirect Pathway ◽  
Jugular Veins ◽  
Arterial Blood ◽  
Arterial Blood Glucose

Previous studies in mice suggest that portal venous infusion of glucose at a low rate paradoxically causes hypoglycemia; this does not occur in dogs, rats, and humans. A possible explanation is that fasting status in the mouse studies may have altered the response. We sought to determine whether the response to portal glucose delivery in the mouse was similar to that seen in other species and whether it was dependent on fasting status. Studies were performed on chronically catheterized conscious mice. Catheters were placed into the portal and jugular veins and carotid artery 5 days before study. After a 5- or 16-h fast, glucose was infused into either the portal (PO) or the jugular vein (JU) for 6 h at 25 μg·g−1·min−1. [3-3H]glucose was infused into the JU to measure glucose turnover. In 5-h-fasted mice, PO and JU exhibited similar increases in arterial blood glucose from 155 ± 11 to 173 ± 19 and 147 ± 8 to 173 ± 10 mg/dl, respectively. Endogenous glucose production decreased and arterial insulin increased to the same extent in both PO and JU. A similar response was observed in 16-h-fasted mice; however, the proportion of hepatic glycogen synthesis occurring by the indirect pathway was increased by fasting. In summary, portal glucose delivery in the mouse did not cause hypoglycemia even when the duration of the fast was extended. The explanation of the differing response from previous reports in the mouse is unclear.

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