Insulin does not mediate the attenuation of fatigue associated with glucose infusion in rat plantaris muscle

2003 ◽  
Vol 95 (1) ◽  
pp. 330-335 ◽  
Author(s):  
Antony D. Karelis ◽  
François Péronnet ◽  
Phillip F. Gardiner

Glucose infusion attenuates fatigue in rat plantaris muscle stimulated in situ, and this is associated with a better maintenance of electrical properties of the fiber membrane (Karelis AD, Péronnet F, and Gardiner PF. Exp Physiol 87: 585–592, 2002). The purpose of the present study was to test the hypothesis that elevated plasma insulin concentration due to glucose infusion (∼900 pmol/l), rather than high plasma glucose concentration (∼10–11 mmol/l), could be responsible for this phenomenon, because insulin has been shown to stimulate the Na+-K+ pump. The plantaris muscle was indirectly stimulated (50 Hz, for 200 ms, 5 V, every 2.7 s) via the sciatic nerve to perform concentric contractions for 60 min, while insulin (8 mU · kg-1 · min-1: plasma insulin ∼900 pmol/l) and glucose were infused to maintain plasma glucose concentration between 4 and 6 [6.2 ± 0.4 mg · kg-1 · min-1: hyperinsulinemic-euglycemic (HE)] or 10 and 12 mmol/l [21.7 ± 1.1 mg · kg-1 · min-1: hyperinsulinemic-hyperglycemic clamps (HH)] (6 rats/group). The reduction in submaximal dynamic force was significantly ( P < 0.05) less with HH (-53%) than with HE and saline only (-66 and -70%, respectively). M-wave characteristics were also better maintained in the HH than in HE and control groups. These results demonstrate that the increase in insulin concentration is not responsible for the increase in muscle performance observed after the elevation of circulating glucose.

1979 ◽  
Vol 236 (4) ◽  
pp. E328 ◽  
Author(s):  
R A DeFronzo ◽  
A D Beckles

The effect of chronic metabolic acidosis (0.1 g/(kg . day) X 3 days) on carbohydrate metabolism was examined with the glucose-clamp technique in 16 healthy volunteers. Hyperglycemic clamp. Plasma glucose concentration is acutely raised and maintained 125 mg/dl above the basal level. Because the glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism (M). Following NH4Cl, M decreased from 8.95 +/- 1.12 to 7.35 +/- 0.76 (P less than 0.05) despite an increased plasma insulin concentration (I) 23 +/- 9%, P less than 0.05). Consequently the M/I ratio, an index of tissue sensitivity to insulin, decreased by 32 +/- 5% (P less than 0.005). Euglycemic clamp. Plasma insulin concentration is acutely raised and maintained 101 +/- 3 microU/ml above basal and plasma glucose is held constant at the fasting level by a variable glucose infusion (M). Following NH4Cl both M and M/I decreased by 15 +/- 4% (P = 0.005) and 15 +/- 5% (P = 0.01), respectively. Metabolic acidosis had no effect on basal [3-3H]glucose production or the percent of decline (91 +/- 4%) following hyperinsulinemia. Both hyperglycemic and euglycemic clamp studies indicate that impaired glucose metabolism following metabolic acidosis results from impaired tissue sensitivity to insulin.


2011 ◽  
Vol 106 (S1) ◽  
pp. S101-S104 ◽  
Author(s):  
Adrian K. Hewson-Hughes ◽  
Matthew S. Gilham ◽  
Sarah Upton ◽  
Alison Colyer ◽  
Richard Butterwick ◽  
...  

Data from intravenous (i.v.) glucose tolerance tests suggest that glucose clearance from the blood is slower in cats than in dogs. Since different physiological pathways are activated following oral administration compared with i.v. administration, we investigated the profiles of plasma glucose and insulin in cats and dogs following ingestion of a test meal with or without glucose. Adult male and female cats and dogs were fed either a high-protein (HP) test meal (15 g/kg body weight; ten cats and eleven dogs) or a HP+glucose test meal (13 g/kg body-weight HP diet+2 g/kg body-weight d-glucose; seven cats and thirteen dogs) following a 24 h fast. Marked differences in plasma glucose and insulin profiles were observed in cats and dogs following ingestion of the glucose-loaded meal. In cats, mean plasma glucose concentration reached a peak at 120 min (10·2, 95 % CI 9·7, 10·8 mmol/l) and returned to baseline by 240 min, but no statistically significant change in plasma insulin concentration was observed. In dogs, mean plasma glucose concentration reached a peak at 60 min (6·3, 95 % CI 5·9, 6·7 mmol/l) and returned to baseline by 90 min, while plasma insulin concentration was significantly higher than pre-meal values from 30 to 120 min following the glucose-loaded meal. These results indicate that cats are not as efficient as dogs at rapidly decreasing high blood glucose levels and are consistent with a known metabolic adaptation of cats, namely a lack of glucokinase, which is important for both insulin secretion and glucose uptake from the blood.


1979 ◽  
Vol 237 (3) ◽  
pp. E214 ◽  
Author(s):  
R A DeFronzo ◽  
J D Tobin ◽  
R Andres

Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.


1995 ◽  
Vol 82 (5) ◽  
pp. 1154-1159 ◽  
Author(s):  
Dounia Sbai ◽  
Philippe Jouvet ◽  
Anne Soulier ◽  
Luc Penicaud ◽  
Jacques Merckx ◽  
...  

Background It should be possible to avoid variations in plasma glucose concentration during anesthesia by adjusting glucose infusion rate to whole-body glucose uptake. To study this hypothesis, we measured glucose utilization and production, before and during halothane anesthesia. Methods After an overnight fast, six adolescents between 12 and 17 yr of age were infused with tracer doses of [6,6-2H2]glucose for 2 h before undergoing anesthesia, and the infusion was continued after induction, until the beginning of surgery. Plasma glucose concentration was monitored throughout, and free fatty acids, lactate, insulin, and glucagon concentrations were measured before and during anesthesia. Results Despite the use of a glucose-free maintenance solution, plasma glucose concentration increased slightly but significantly 5 min after induction (5.3 +/- 0.4 vs. 4.5 +/- 0.4 mmol.l-1, P &lt; 0.05). This early increase corresponded to a significant increase in endogenous glucose production over basal conditions (4.1 +/- 0.4 vs. 3.6 +/- 0.2 mg.kg-1.min-1, P &lt; 0.05), with no concomitant change in peripheral glucose utilization. Fifteen minutes after induction, both glucose utilization and production rates decreased steadily and were 20% less than basal values by 35 min after induction (2.9 +/- 0.3 vs. 3.6 +/- 0.2 mg.kg-1.min-1, P &lt; 0.05). Similarly, glucose metabolic clearance rate decreased by 25% after 35 min. Despite the increase in blood glucose concentration, anesthesia resulted in a significant decrease in plasma insulin concentration. Conclusions These data suggest that halothane anesthesia per se affects glucose metabolism. The decrease in peripheral glucose utilization and metabolic clearance rates and the blunted insulin release question the relevance of glucose infusion in these clinical settings.


2000 ◽  
Vol 164 (1) ◽  
pp. 1-6 ◽  
Author(s):  
CT Musabayane ◽  
O Munjeri ◽  
P Bwititi ◽  
EE Osim

We report successful oral administration of insulin entrapped in amidated pectin hydrogel beads in streptozotocin (STZ)-diabetic rats, with a concomitant reduction in plasma glucose concentration. The pectin-insulin (PI) beads were prepared by the gelation of humilin-pectin solutions in the presence of calcium. Separate groups of STZ-diabetic rats were orally administered two PI beads (30 micrograms insulin) once or twice daily or three beads (46 micrograms) once daily for 2 weeks. Control non-diabetic and STZ-diabetic rats were orally administered pectin hydrogel drug-free beads. By comparison with control non-diabetic rats, untreated STZ-diabetic rats exhibited significantly low plasma insulin concentration (0.32+/-0. 03 ng/ml, n=6, compared with 2.60+/-0.44 ng/ml in controls, n=6) and increased plasma glucose concentrations (25.84+/-1.44 mmol/l compared with 10.72+/- 0.52 mmol/l in controls). Administration of two PI beads twice daily (60 micrograms active insulin) or three beads (46 micrograms) once a day to STZ-diabetic rats increased plasma insulin concentrations (0.89+/-0.09 ng/ml and 1.85+/- 0.26 ng/ml, respectively), with a concomitant reduction in plasma glucose concentration (15.45+/-1.63 mmol/l and 10.56+/-0.26 mmol/l, respectively). However, a single dose of PI beads (30 micrograms) did not affect plasma insulin concentrations, although plasma glucose concentrations (17.82+/-2.98 mmol/l) were significantly reduced compared with those in untreated STZ-diabetic rats. Pharmacokinetic parameters in STZ-diabetic rats show that the orally administered PI beads (30 micrograms insulin) were more effective in sustaining plasma insulin concentrations than was s.c. insulin (30 micrograms). The data from this study suggest that this insulin-loaded amidated pectin hydrogel bead formulation not only produces sustained release of insulin, but may also reduce plasma glucose concentration in diabetes mellitus.


1974 ◽  
Vol 62 (2) ◽  
pp. 299-309 ◽  
Author(s):  
J. M. BASSETT ◽  
DENISE MADILL

SUMMARY Chronically cannulated foetal lambs close to term were infused intravenously with glucose at rates of 40 or 70 mg/min for up to 5 days. Infusion at these rates increased the foetal plasma glucose concentration to values in the ranges 35–45 and 60–80 mg/100 ml respectively. There were related increases in plasma fructose and lactate concentrations. Foetal plasma insulin concentrations increased within the first hour and remained raised throughout infusion. Plasma insulin concentrations were significantly correlated with plasma glucose concentrations. The secretory response of insulin to subsequent glucose infusions at a rate of 140 mg/min was not increased by the previous prolonged glucose infusions. Glucose infusion resulted in decreased plasma growth hormone concentrations in three of the lambs infused, but over the total number of observations plasma glucose and growth hormone concentrations were not significantly correlated.


1970 ◽  
Vol 46 (2) ◽  
pp. 243-260 ◽  
Author(s):  
D. R. LANGSLOW ◽  
E. J. BUTLER ◽  
C. N. HALES ◽  
A. W. PEARSON

SUMMARY The relationships between plasma insulin, glucose, non-esterified fatty acid (NEFA) and α-amino nitrogen concentrations in the domestic fowl have been studied. During a 72-hr. fast the plasma glucose concentration fell while the NEFA concentration rose but there was no change in plasma insulin concentration. Both oral and intracardiac glucose increased the plasma insulin concentration and lowered the plasma NEFA and α-amino nitrogen concentrations. Oral amino acids increased plasma insulin and glucose concentrations but had no effect on plasma NEFA. Intracardiac ox insulin depressed plasma glucose and α-amino nitrogen and increased the plasma NEFA concentration. Intracardiac glucagon increased both plasma glucose and NEFA and depressed the plasma α-amino nitrogen concentrations but had no significant effect on plasma insulin. Intracardiac adrenaline had no effect on plasma NEFA but increased plasma glucose concentration and caused a small depression in plasma insulin concentration.


1988 ◽  
Vol 59 (2) ◽  
pp. 315-322 ◽  
Author(s):  
Susan Southon ◽  
Susan J. Fairweather-Tait ◽  
Christine M. Williams

1. Wistar rats were fed on a control semi-synthetic diet throughout pregnancy, or a control diet in the first 2 weeks and a marginal-zinc diet in the 3rd week of pregnancy. On day 20, after an overnight fast, half the animals in each group were given glucose by gavage and the 0–30 min rise in blood glucose measured in tail blood. After 60 min blood was taken by cardiac puncture for glucose and insulin assay. Maternal pancreases were removed and the Zn contents measured. Fetuses from each litter were combined for wet/dry weights, protein and DNA determinations.2. Plasma insulin concentration was higher, and glucose concentration and pancreatic Zn content lower, in pregnantv. non-pregnant animals of similar age, fed on the same diet. Pancreatic Zn content was lowest in the marginal-Zn group of pregnant rats. Fetuses from mothers fed on the marginal-Zn diet during the last week of pregnancy were slightly heavier than controls and had a significantly higher protein: DNA ratio. The 0–30 min rise in blood glucose was significantly greater in the marginal-Zn animals.3. In a second experiment, pregnant rats were given similar diets to those used in the first study, but the marginal-Zn diet was given for a shorter period (days 15–19 of pregnancy). On day 19 the rats were meal-fed and on day 20, after an overnight fast, an oral glucose dose was administered. Tail-blood was taken at timed intervals up to 60 min post-dosing for glucose assay. Both maternal and fetal blood glucose and insulin concentration was measured 70 min post-dosing.4. Values for maternal and fetal blood glucose and plasma insulin, measured 70 min after the administration of a glucose dose, were similar in the two groups, but the initial rise in blood glucose concentration was again significantly higher in pregnant rats given the marginal-Zn diet towards term.5. It is suggested that the change in growth and composition, observed in fetuses from rats given a marginal-Zn diet in later pregnancy, is associated with altered maternal carbohydrate metabolism.


1971 ◽  
Vol 125 (2) ◽  
pp. 541-544 ◽  
Author(s):  
R. A. Hawkins ◽  
K. G. M. M. Alberti ◽  
C. R. S. Houghton ◽  
D. H. Williamson ◽  
H. A. Krebs

1. Sodium acetoacetate was infused into the inferior vena cava of fed rats, 48h-starved rats, and fed streptozotocin-diabetic rats treated with insulin. Arterial blood was obtained from a femoral artery catheter. 2. Acetoacetate infusion caused a fall in blood glucose concentration in fed rats from 6.16 to 5.11mm in 1h, whereas no change occurred in starved or fed–diabetic rats. 3. Plasma free fatty acids decreased within 10min, from 0.82 to 0.64mequiv./l in fed rats, 1.16 to 0.79mequiv./l in starved rats and 0.83 to 0.65mequiv./l in fed–diabetic rats. 4. At 10min the plasma concentration rose from 20 to 49.9μunits/ml in fed unanaesthetized rats and from 6.4 to 18.5μunits/ml in starved rats. There was no change in insulin concentration in the diabetic rats. 5. Nembutal-anaesthetized fed rats had a more marked increase in plasma insulin concentration, from 30 to 101μunits/ml within 10min. 6. A fall in blood glucose concentration in fed rats and a decrease in free fatty acids in both fed and starved rats is to be expected as a consequence of the increase in plasma insulin. 7. The fall in the concentration of free fatty acids in diabetic rats may be due to a direct effect of ketone bodies on adipose tissue. A similar effect on free fatty acids could also be operative in normal fed or starved rats.


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