Effects of cold exposure and time relative to feeding on glucose metabolism of sheep using a glucose clamp approach

2003 ◽  
Vol 140 (3) ◽  
pp. 335-341 ◽  
Author(s):  
A. TAKEBAYASHI ◽  
H. SANO ◽  
T. FUJITA ◽  
K. AMBO

An experiment combining a hyperinsulinaemic euglycaemic clamp approach and an isotope dilution method determined the effects of cold exposure and time relative to feeding on blood glucose metabolism in four sheep. The sheep, fed 20 g/kg body-weight (BW) of lucerne hay cubes and 5 g/kg BW of maize-based concentrates once daily, were exposed in turn to a thermoneutral environment (20 °C) and a cold environment (0 °C) for 20 days. The combined experiments were performed at four different times relative to feeding, i.e. 3 to 2 h, 2 to 1 h and 1 to 0 h before, and 1 to 2 h after the initiation of feeding for the basal periods, and 1 to 0 h before, and 0 to 1 h, 1 to 2 h and 3 to 4 h after the initiation of feeding for the glucose clamp periods in both environments. [U-13C]Glucose was continuously infused for 6 h after a priming injection. Insulin was continuously infused at 6·0 mU/kg BW per min for 2 h, which corresponded to the last 2 h of the [U-13C]glucose infusion. Blood glucose concentrations were maintained euglycaemic during the insulin infusion by concomitant variable glucose infusion. Blood glucose turnover rate (GTR) during the basal period was enhanced by cold exposure (P=0·01) and feeding (P=0·04). Blood GTR increased (P<0·01) with the glucose clamp. During the glucose clamp, blood GTR and glucose infusion rate (GIR) were greater (P=0·003 and P=0·001, respectively) during cold exposure than in the thermoneutral environment. Time relative to feeding influenced (P=0·003) the GIR, whereas changes in blood GTR and endogenous glucose production rate were not significant. No significant cold×feeding interaction was observed in these variables. It was suggested that, in sheep, glucose metabolism was enhanced by cold exposure and the glucose clamp. It was probable that blood glucose metabolism during the glucose clamp was influenced by cold exposure and feeding, but the combined effect of cold exposure and feeding was not significant.

2000 ◽  
Vol 134 (3) ◽  
pp. 319-325 ◽  
Author(s):  
H. SANO ◽  
S. KONNO ◽  
A. SHIGA

An isotope dilution method using [U-13C]glucose and a glucose clamp approach were applied to determine the effects of supplemental chromium (Cr) and heat exposure on blood glucose metabolism and tissue responsiveness and sensitivity to insulin in sheep. The sheep consumed diets with either 0 or 1 mg of Cr/kg (Control and +Cr diet, respectively) from high-Cr-yeast, and were exposed from a thermoneutral environment (20 °C) to a hot environment (30 °C) for 5 days. Blood glucose turnover rate did not differ between the diets, and was lower (P < 0·05) during heat exposure than in the thermoneutral environment. The maximal glucose infusion rate (tissue responsiveness to insulin) tended to be lower (P = 0·06) for the +Cr diet than for the Control diet, but did not change with heat exposure. The plasma insulin concentration at half maximal glucose infusion rate (tissue sensitivity to insulin) did not differ between the diets, and was greater (P < 0·05) during heat exposure than in the thermoneutral environment. No significant diet × environment interactions were observed. There was no significant evidence that Cr supplementation moderated heat stress in sheep from the measures of blood glucose metabolism and insulin action.


1989 ◽  
Vol 257 (2) ◽  
pp. R350-R357 ◽  
Author(s):  
J. A. Owens ◽  
J. Falconer ◽  
J. S. Robinson

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.


2001 ◽  
Vol 86 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Sylvie Normand ◽  
Yadh Khalfallah ◽  
Corinne Louche-Pelissier ◽  
Christiane Pachiaudi ◽  
Jean-Michel Antoine ◽  
...  

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.


1987 ◽  
Vol 252 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
G. Paolisso ◽  
A. J. Scheen ◽  
A. S. Luyckx ◽  
P. J. Lefebvre

To study the metabolic effects of pulsatile glucagon administration, six male volunteers were submitted to a 260-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of the pancreatic hormones was inhibited by somatostatin (100 micrograms X h-1), basal insulin secretion was replaced by a continuous insulin infusion (0.2 mU X kg-1 X min-1), and glucagon was infused intravenously in two conditions at random: either continuously (125 ng X min-1) or intermittently (812.5 ng X min-1, with a switching on/off length of 2/11 min). Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classical methodology using a D-[3-3H]glucose infusion allowed us to study glucose turnover. While basal plasma glucagon levels were similar in both conditions (122 +/- 31 vs. 115 +/- 18 pg X ml-1), they plateaued at 189 +/- 38 pg X ml-1 during continuous infusion and varied between 95 and 501 pg X ml-1 during pulsatile infusion. When compared with continuous administration, pulsatile glucagon infusion initially induced a similar increase in endogenous (hepatic) glucose production and blood glucose, did not prevent the so-called “evanescent” effect of glucagon on blood glucose, and after 3 h tended to reduce rather than increase hepatic glucose production. In conclusion, in vivo pulsatile hyperglucagonemia in normal man fails to increase hepatic glucose production.


1989 ◽  
Vol 257 (5) ◽  
pp. E686-E696 ◽  
Author(s):  
G. Paolisso ◽  
A. J. Scheen ◽  
A. Albert ◽  
P. J. Lefebvre

The purpose of the present study was to investigate the respective effects of continuous intravenous delivery of both insulin and glucagon compared with those of pulsatile insulin (and continuous glucagon), pulsatile glucagon (and continuous insulin) and both hormones administered in a pulsatile manner (but out of phase) on various parameters of glucose turnover. The study was performed on six healthy male volunteers submitted to a 325-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of pancreatic hormones was inhibited by somatostatin (2 micrograms/min). Four combinations of continuous and pulsatile infusions of insulin and glucagon were performed on different days and in random order. The amounts of hormone infused were identical in all instances and were 0.2 mU.kg-1.min-1 (continuous insulin), 67 ng/min (continuous glucagon), 1.3 mU.kg-1.min-1 and 435 ng/min with a switching on-off length of 2-11 min (for intermittent insulin and glucagon delivery, respectively). In the case of pulsatile administration of both hormones, the pulses of insulin and glucagon were given out of phase with a 6-min interval. Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classic methodology using a D-[3-3H]glucose infusion allowed to study glucose turnover. When compared with pulsatile insulin and continuous glucagon, pulsatile glucagon and continuous insulin were characterized by a significantly higher endogenous (hepatic) glucose production. When both insulin and glucagon were delivered in a pulsatile manner, the effect of pulsatile glucagon was predominant, maintaining a high endogenous glucose production. Under no circumstance was an effect on glucose utilization or clearance detected. This study demonstrates that pulsatile delivery of insulin or glucagon in humans has greater effects in modulating endogenous glucose production than continuous infusion. Furthermore, when both insulin and glucagon are delivered intermittently and out of phase, the stimulatory effect of glucagon on endogenous glucose production prevails over the inhibitory effect of insulin.


1968 ◽  
Vol 46 (3) ◽  
pp. 391-398 ◽  
Author(s):  
G. Hetenyi Jr. ◽  
G. A. Wrenshall

The intravenous infusion of glucose at rates corresponding to 17–79% of the endogenous (hepatic) rate of glucose production decreased the latter in both normal and diabetic dogs. The increase in the rate of the exogenous infusion and the decrease in the rate of endogenous production were found to be positively correlated. The correlation between the change in the rate of glucose disappearance (utilization plus excretion) and the change in the rate of the exogenous infusion was significant in normal but not in diabetic dogs. The infusion of galactose had no effect on endogenous glucose production. Infusions into the cephalic vein or into the carotid artery were equally effective in decreasing endogenous glucose production. It appears that the rate of endogenous (hepatic) glucose production adapts to an exogenous glucose infusion in both normal and diabetic dogs. Such an adaptation in the rate of glucose disappearance (disposal) was observed only in normal but not in pancreatectomized dogs. Thus the role of the release of insulin in such adaptation is to increase the disposal rather than to decrease the rate of the endogenous production of glucose. The specificity of the adaptive mechanism is demonstrated by the ineffectiveness of galactose in altering glucose turnover.


1985 ◽  
Vol 54 (2) ◽  
pp. 449-458 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong

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.


1996 ◽  
Vol 270 (4) ◽  
pp. E709-E717 ◽  
Author(s):  
J. A. Tayek ◽  
J. Katz

Eight normal controls and nine non-insulin-dependent diabetes mellitus diabetics were, after an overnight fast, infused for 3 h with [6-3H]- and with [U-13C]glucose with six 13C carbons at rates from 0.03 to 0.15 mg.kg-1.min-1. Plasma glucose and lactate were assayed by gas chromatography-mass spectroscopy. Several parameters of glucose metabolism were calculated from the mass isotopomer distribution. Glucose production (GP) determined with [6-3H]- and [U-13C]glucose agreed closely. GP was 1.9 +/- 0.16 (range 1.3-2.5) mg.kg-1.min-1 in controls and 2.8 +/- 0.29 (1.7-4.5) mg.kg-1.min-1 in diabetics (P < 0.05). The correlation in diabetes between plasma glucose and GP (r = 0.911, P < 0.01) was close. Recycling of carbon (8 vs 7%) dilution by unlabeled carbon (2- vs 2.3-fold), and dilution via the tricarboxylic acid cycle (1.5-fold) were similar in controls and diabetics. Gluconeogenesis was 0.90 +/- 0.08 (0.5-1.3) mg.kg-1.min-1 in controls and 1.30 +/- 0.13 (0.8-1.9) mg.kg-1.min-1 in diabetics (P < 0.05). Gluconeogenesis contributions to GP were 46.6 +/- 4.0% (26-61%) in the controls and 48.8 +/- 5.7% (32-83%) in diabetics. We show that, using [U-13C]glucose infusion of 2-5% of glucose turnover (0.03-0.10 mg.kg-1.min-1), a large number of parameters of glucose metabolism may be determined in humans.


1978 ◽  
Vol 234 (1) ◽  
pp. E84 ◽  
Author(s):  
J Radziuk ◽  
K H Norwich ◽  
M Vranic

The aim of the present experiments is to validate, in conscious dogs, the tracer infusion methods of measuring nonsteady turnover rates. This was done in nine experiments performed in four normal dogs by infusing isotopically labeled glucose (2-3H, 6-3H, 1-14C) and monitoring the concentrations of both the labeled and unlabeled substances. The validation is based on the observation that a high exogenous infusion of glucose will suppress endogenous glucose production and become the sole source of glucose in the body. By infusing glucose at a high, time-varying rate, calculating its rate of appearance, (Ra) and comparing it to the infused rate, the method can be verified. The calculations were based on: a) a single-compartment model with a modified volume of distribution; b) a two-compartment model; and c) a generalized dispersion model. The absolute values of the areas of the deviations of the calculated from the infused curves were found to be, respectively, 9.5, 8.4, and 7.8 percent of the total area under the infused curve. It was concluded that the tracer infusion method can reliably measure Ra of glucose when it is changing rapidly, and the system is out of steady state.


1997 ◽  
Vol 273 (6) ◽  
pp. E1209-E1215 ◽  
Author(s):  
Visvanathan Chandramouli ◽  
Karin Ekberg ◽  
William C. Schumann ◽  
Satish C. Kalhan ◽  
John Wahren ◽  
...  

The use of2H2O in estimating gluconeogenesis’ contribution to glucose production (%GNG) was examined during progressive fasting in three groups of healthy subjects. One group ( n = 3) ingested2H2O to a body water enrichment of ≈0.35% 5 h into the fast. %GNG was determined at 2-h intervals from the ratio of the enrichments of the hydrogens at C-5 and C-2 of blood glucose, assayed in hexamethylenetetramine. %GNG increased from 40 ± 8% at 10 h to 93 ± 6% at 42 h. Another group ingested2H2O over 2.25 h, beginning at 11 h ( n = 7) and 19 h ( n = 7) to achieve ≈0.5% water enrichment. Enrichment in plasma water and at C-2 reached steady state ≈1 h after completion of2H2O ingestion. The C-5-to-C-2 ratio reached steady state by the completion of 2H2O ingestion. %GNG was 54 ± 2% at 14 h and 64 ± 2% at 22 h. A 3-h [6,6-2H2]glucose infusion was also begun to estimate glucose production from enrichments at C-6, again in hexamethylenetetramine. Glucose produced by gluconeogenesis was 0.99 ± 0.06 mg ⋅ kg−1 ⋅ min−1at both 14 and 22 h. In a third group ( n = 3) %GNG reached steady state ≈2 h after2H2O ingestion to only ≈0.25% enrichment. In conclusion, %GNG by 2 h after2H2O ingestion and glucose production using [6,6-2H2]glucose infusion, begun together, can be determined from hydrogen enrichments at blood glucose C-2, C-5, and C-6. %GNG increases gradually from the postabsorptive state to 42 h of fasting, without apparent change in the quantity of glucose produced by gluconeogenesis at 14 and 22 h.


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