scholarly journals Effects of Somatostatin and Glucagon on the Utilization of [2_14C] Propionate in Glucose Production in Vivo in Sheep

1980 ◽  
Vol 33 (4) ◽  
pp. 457 ◽  
Author(s):  
Ronald P Brockman ◽  
Cindy Greer

This study examined the effects of hypoglucagonaemia and hyperglucagonaemia on the incorporation of 14C from [2-14C]propionate into plasma glucose of sheep in vivo. The sheep were adult ewes fed a maintenance diet of lucerne pellets delivered in equal aliquots hourly. The irreversible loss of glucose was determined by the continuous infusion of [6-3H]glucose. During the control period (the hour immediately preceding infusion of hormones) 63 �2 % of the propionate was converted to glucose, accounting for 30�2 % of glucose production. Glucagon deficiency, induced by infusion of somatostatin (100 J1g/h), did not affect gluconeogenesis and the irreversible loss of glucose significantly. However, glucagon infusion at 11 �5 �O� 6 J1g/h significantly increased the irreversible loss of glucose, with the greatest increase occurring in the first 15 min of infusion. The 14C specific radioactivity of glucose and the fraction of glucose derived from propionate decreased significantly during glucagon infusion. The data are consistent with glucagon having a marked glycogenolytic effect initially, but little or no selective effect in promoting the utilization of propionate for glucose synthesis in vivo in sheep.

1974 ◽  
Vol 142 (1) ◽  
pp. 171-183 ◽  
Author(s):  
Joseph Katz ◽  
Arnold Dunn ◽  
Maymie Chenoweth ◽  
Sybil Golden

1. Glucose labelled with 3H in position 2 and uniformly with 14C was administered simultaneously to rabbits and rats either as a single injection or by continuous infusion. Plasma glucose specific radioactivity and the yield of 3H in the plasma water were monitored. 2. The rates of synthesis, recycling of carbon and total body mass of glucose were calculated, without assuming a multicompartmental model and without fitting data by exponential expressions. 3. The rate of synthesis of glucose in starved-overnight rabbits was 4mg/min per kg (range 3–4.5mg/min per kg) and 25–35% of the glucose carbon was recycled. The mass of total body glucose in starved rabbits was 290mg/kg (range 220–390mg/kg). About one-third of the total body glucose equilibrates nearly instantaneously with plasma glucose. 4. In rats starved overnight, glucose synthesis was about 10mg/min per kg and recycling of carbon ranged from 30–40%. Total body mass (per kg body weight) is similar to that in rabbits. 5. The activity in plasma water after injection of [2-3H]glucose was determined. The initial rate of 3H2O formation is rapid, indicating that the major site of glucose catabolism is in the rapidly mixing pool. The curve of total body glucose radioactivity was obtained from the 3H2O yield, and total mass of glucose was calculated. This agrees with that obtained from the 3H specific-radioactivity curve.


1979 ◽  
Vol 57 (11) ◽  
pp. 1267-1274 ◽  
Author(s):  
John R. Allsop ◽  
Robert R. Wolfe ◽  
Joseph J. DiStephano III ◽  
John F. Burke

The rate of appearance of unlabelled glucose was calculated from changes in plasma glucose specific radioactivity after a single intravenous injection of labelled glucose and compared with the actual constant infusion rate of unlabelled glucose into an anaesthetized dog with all sources of endogenous glucose production surgically removed. The mean steady-state rate of appearance of unlabelled glucose calculated from the area under the specific radioactivity versus time curve was 7% higher than the actual infusion rate (n = 4), but the difference was not statistically significant. The variability in the rate calculated in this manner was, however, greater than the variability we have reported with rates determined from a primed constant infusion of tracer. Using 15- to 60- or 60- to 120-min specific radioactivity data the mean rate of appearance of glucose, calculated on the assumption of a one-pool model for glucose turnover in vivo, was approximately 60% higher than the actual infusion rate. The results also indicate that it is possible to construct multi-pool models, but it is difficult to equate specific physiological events with the individual terms of the multi-exponential equation which describes the changes in plasma glucose specific radioactivity.


1982 ◽  
Vol 47 (1) ◽  
pp. 87-94 ◽  
Author(s):  
N. Chaiyabutr ◽  
Anne Faulkner ◽  
M. Peaker

1. Glucose turnover (i.e. glucose entry and utilization rates) in fed and 48 h starved goats during pregnancy and lactation was determined using a continuous infusion of [U-14C]- and [3-3H]glucose.2. Glucose synthesis and utilization increased during pregnancy and lactation in fed but not in starved goats.3. Recycling of giucosc-C was approximately 10% in fed animals and 15–20% in starved animals and was unaffected by the stage of pregnancy or lactation.4. Plasma glucose concentrations were maintained during pregnancy and lactation in fed goats but decreased during 48 h starvation in pregnant goats. Little change was seen in the plasma concentration of lipids and their metabolites during pregnancy and lactation in fed goats, but increases were observed after 48 h starvation.5. The control of glucose metabolism in ruminants during pregnancy and lactation is discussed.


1973 ◽  
Vol 29 (2) ◽  
pp. 175-195 ◽  
Author(s):  
G. J. Judson ◽  
R. A. Leng

1. Short-term effects of infusions of propionate, amino acids and butyrate on gluconeogenesis, as indicated by changes in the irreversible loss of plasma glucose, synthesis of glucose from ruminal propionate or fixation of blood bicarbonate into glucose have been examined in sheep given their daily ration in twenty-four equal portions at hourly intervals.Sheep received intravenous infusions of [6-3H]glucose usually, in combination with [U-14C]glucose or NaH14CO3or with intraruminal infusions of [2-14C]propionate. Substrates were infused over a 3–7 h period and followed estimates of pre-infusion kinetic measurements.2. It was demonstrated that intraruminal and intramesenteric vein infusions of sodium propionate and intra-abomasal infusions of casein hydrolysate stimulated gluconeogenesis. Glucose synthesis showed a linear response to the infusion of these substrates, which varied from 0·35–6·35 mmol propionate/min and 50–160 mg casein/min.3. The increment in the measured production rate of propionate in the rumen was consistently less than the rate of addition of propionate to the rumen.4. Intramesenteric vein infusions of sodium butyrate at successive rates of 0·25 and 0·50 mmol/min produced only an initial transient increase in plasma glucose production. Since the rate of glucose synthesis from ruminal propionate was not altered, it was suggested that butyrate initiated glycogen mobilization.


1993 ◽  
Vol 121 (1) ◽  
pp. 125-130 ◽  
Author(s):  
Y. Obara ◽  
D. W. Dellow

SUMMARYThe effect of rumen fermentation on the relationship between urea and glucose kinetics was examined in sheep fed chopped lucerne hay with intraruminal infusions of water, urea, sucrose, or urea plus sucrose at Palmerston North, New Zealand in 1986. Sheep were fed hourly and infused intraruminally with water (1200 m1/day), or a similar volume containing either urea alone (13·7g/day), sucrose alone (178·2 g/day) or urea (14·6 g/day) plus sucrose (175·0 g/day). The added sucrose resulted in a lower rumen ammonia concentration (P< 0·05), lower plasma urea concentration (P< 0·05) and reduced urinary urea excretion (P< 0·05). Urea recycled to the gut tended to increase with the sucrose, urea or sucrose plus urea treatments compared with the water treatment. The fermentation of sucrose in the rumen resulted in decreases in ruminal pH (P< 0·05) and in the ratio of acetate to propionate (A:P) (P< 0·05). The infusion of sucrose also increased the concentration of propionate in rumen fluid (P< 0·05), tended to increase the plasma glucose level and increased plasma glucose irreversible loss (P< 0·05). The infusion of urea resulted in an increase in the plasma urea level (P< 0·05), urea pool size (P< 0·05) and urea irreversible loss (P< 0·01). However, urea infusion did not affect glucose metabolism or volatile fatty acid (VFA) fermentation. The effects of sucrose infusion on glucose and urea kinetics were broadly similar when given alone or with urea, apart from changes in the urea degradation rate. It was concluded that the additional fermentative activity resulting from sucrose increased propionate production which, in turn, was available for glucose production, thus ‘sparing’ amino acids for tissue protein utilization and reducing urea excretion.


1983 ◽  
Vol 244 (6) ◽  
pp. E596-E602 ◽  
Author(s):  
A. D. Cherrington ◽  
W. W. Lacy ◽  
P. E. Williams ◽  
K. E. Steiner

Somatostatin is widely used to inhibit insulin and glucagon release by the pancreas in studies of metabolic regulation in vivo. To determine whether the peptide can directly modify the metabolic effects of an increment in glucagon in overnight-fasted conscious dogs, glucagon was increased in the presence (+S) or absence (-S) of somatostatin. Either somatostatin (+S; 0.8 microgram . kg-1 . min-1) or a two-stage pancreatectomy (-S) was used to inhibit the endocrine pancreas, and at the same time replacement infusions of insulin (285-300 microU . kg-1 .min-1) and glucagon (0.65 ng . kg-1 . min-1) were given. After a 40-min control period the plasma glucagon level was raised fourfold in the presence of fixed basal insulin. Plasma insulin in both groups were similar [11 +/- 2 (+S) and 9 +/- 1 (-S) microU/ml]. Glucagon rose from 64 +/- 11 to 225 +/- 19 and 92 +/- 11 to 219 +/- 20 pg/ml in the +S and -S groups, respectively. Tracer-determined ([3-3H]glucose) glucose production rose by 5.28 +/- 1.02 (+S) and 4.25 +/- 1.12 (-S) mg . kg-1 . min-1 at 15 min and fell similarly over 3 h in both groups. Plasma glucose rose similarly in both groups peaking at 195 +/- 15 (+S) and 174 +/- 8 (-S) mg/dl. Plasma alanine fell similarly over 3 h [133 +/- 35 (+S) and 138 +/- 42 (-S) mumol/liter]. Conversion of [14C]alanine and [14C]-lactate to [14C]glucose rose progressively over 3 h in both groups, eventually being elevated by 210 +/- 58 (+S) and 148 +/- 48% (-S). We conclude that in the dog somatostatin at the dose used does not alter the effect of an increment in glucagon on carbohydrate metabolism.


2015 ◽  
Vol 309 (2) ◽  
pp. E191-E203 ◽  
Author(s):  
Clinton M. Hasenour ◽  
Martha L. Wall ◽  
D. Emerson Ridley ◽  
Curtis C. Hughey ◽  
Freyja D. James ◽  
...  

Mouse models designed to examine hepatic metabolism are critical to diabetes and obesity research. Thus, a microscale method to quantitatively assess hepatic glucose and intermediary metabolism in conscious, unrestrained mice was developed. [13C3]propionate, [2H2]water, and [6,6-2H2]glucose isotopes were delivered intravenously in short- (9 h) and long-term-fasted (19 h) C57BL/6J mice. GC-MS and mass isotopomer distribution (MID) analysis were performed on three 40-μl arterial plasma glucose samples obtained during the euglycemic isotopic steady state. Model-based regression of hepatic glucose and citric acid cycle (CAC)-related fluxes was performed using a comprehensive isotopomer model to track carbon and hydrogen atom transitions through the network and thereby simulate the MIDs of measured fragment ions. Glucose-6-phosphate production from glycogen diminished, and endogenous glucose production was exclusively gluconeogenic with prolonged fasting. Gluconeogenic flux from phospho enolpyruvate (PEP) remained stable, whereas that from glycerol modestly increased from short- to long-term fasting. CAC flux [i.e., citrate synthase ( V CS)] was reduced with long-term fasting. Interestingly, anaplerosis and cataplerosis increased with fast duration; accordingly, pyruvate carboxylation and the conversion of oxaloacetate to PEP were severalfold higher than V CS in long-term fasted mice. This method utilizes state-of-the-art in vivo methodology and comprehensive isotopomer modeling to quantify hepatic glucose and intermediary fluxes during physiological stress in mice. The small plasma requirements permit serial sampling without stress and the affirmation of steady-state glucose kinetics. Furthermore, the approach can accommodate a broad range of modeling assumptions, isotope tracers, and measurement inputs without the need to introduce ad hoc mathematical approximations.


1979 ◽  
Vol 57 (7) ◽  
pp. 767-770 ◽  
Author(s):  
G. Hetenyi Jr.

Based on a previously designed method for the estimation of the contribution of C-atoms by acetylcoenzyme A to the hepatic oxaloacetate pool, the loss of 14C-atoms on their way from a precursor to plasma glucose due to 'metabolic exchange' was estimated in normal and diabetic dogs and in normal rats. Due to this loss of 14C-atoms, the rates of gluconeogenesis when calculated from the transfer of 14C-atoms from precursors (other than glycerol) are underestimated by a factor of 2.2 ± 0.07 in normal, 1.8 ± 0.05 in diabetic dogs, and by 1.55 ± 0.04 in normal rats.


1988 ◽  
Vol 117 (4) ◽  
pp. 457-462 ◽  
Author(s):  
Ralph W. Stevenson ◽  
Nowell Stebbing ◽  
Theodore Jones ◽  
Keith Carr ◽  
Peter M. Jones ◽  
...  

Abstract. hGH32-38 was tested to determine if the peptide could affect hepatic glucose production in the conscious dog under basal conditions (euglycemia) or if it could enhance glucose uptake when hyperglycemia was induced. hGH32-38 (1.6 nmol · kg−1 · min−1) or vehicle was infused in a cross-over design study into each of 4 conscious 16 h-fasted dogs for 3 h (0–180 min) following a 40 min control period. At 90 min, plasma glucose was raised to and maintained at 9.4 mmol/l by glucose infusion for 3 h (until 270 min). Neither hGH32-38 nor vehicle infusion had a significant effect on insulin and glucagon levels or on tracer determined ([3-3H]glucose) glucose production. As a result, neither treatment changed plasma glucose (5.72 ± 0.17 to 5.78 ± 0.17 mmol/l with hGH32-38; 5.50 ± 0.22 to 5.50 ± 0.17 mmol/l with vehicle). Induction of hyperglycemia (9.4 mmol/l) caused glucagon concentrations to fall similarly to about 50 ng/l with and without hGH32-38. Insulin rose to similar levels in both protocols, yet more glucose was required to maintain the same hyperglycemia with hGH32-38 (135– 180 min) (74.9 ± 12.7 vs 43.7 ± 7.1 μmol · kg−1 · min−1, P < 0.05). In summary, hGH32-38 significantly increased glucose disposition during hyperglycemia and this effect may be attributed to enhanced insulin action or to an insulin independent action of the peptide.


1978 ◽  
Vol 172 (3) ◽  
pp. 407-416 ◽  
Author(s):  
J R Allsop ◽  
R R Wolfe ◽  
J F Burke

The rate of appearance of unlabelled glucose was calculated from tracer data and compared with the actual rate of infusion of unlabelled glucose into a anaesthetized dog with all sources of endogenous glucose production surgically removed. The mean steady-state rate of appearance of unlabelled glucose calculated from the equilibrium specific radioactivity was insignificantly higher (0.3%) than the actual rate of infusion of unlabelled glucose (n = 6). During non-steady states, a time-variable volume of distribution of glucose (V) was necessary to predict the rate of appearance of unlabelled glucose correctly from the pool-dependent equation described by Steele [(1959) Ann. N.Y. Acad. Sci. 82, 420–430]. Rapid fluctuations in the rate of appearance of glucose could be predicted reasonably well by using a fixed value of V for 40ml/kg, but by using larger fixed values for V (100–160ml/kg) the rates were inaccurate. The pool-dependent two-radiactive-isotope technique described by Issekutz, Issekutz & Elahi [(1974) Can. J. Physiol. Pharmacol. 52, 215–224] predicted single-step increases in the rate of infusion of glucose reasonably accurately, but the Steele (1959) equation was better at predicting sequential changes in the rate of infusion of unlabelled glucose.


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