A dynamic model to analyse intravenous glucose and insulin tolerance tests performed on dairy cows

A dynamic model was developed to assess insulin sensitivity and pancreatic response in lactating dairy cows. The model is based on a simultaneous analysis of insulin and glucose intravenous tolerance tests. It comprises five compartments corresponding to insulin in portal–hepatic plasma, and insulin or glucose in both systemic plasma and in interstitial fluid. Insulin secretion rate is a sigmoidal function of glucose in plasma. Insulin is cleared from hepatic plasma and from the interstitial fluid. The glucose entry rate is constant and glucose utilization rate is a sigmoidal function of insulin in the interstitial fluid. Six parameters were estimated: two for insulin secretion rate, two for insulin clearance, one for glucose entry rate and one for glucose utilization rate. After integration of the functions, the model yielded a relative estimate of the quantities of insulin secreted and cleared, as well as the glucose entering and utilized during each test. Using an experimental dataset composed of ten pairs of tolerance tests, the explained variations for plasma insulin and glucose concentrations were 96·0 and 98·3 % and standard errors of estimates were 0·032 nmol/l and 0·14 mmol/l respectively. Except in the early stages after injection, residual errors were low. A Jackknife analysis showed that the estimated parameters exhibited low statistical bias. This model simplifies the interpretation of both tests through a simulation based on six common parameters. Compared to a classical analysis of tolerance tests, it may improve the analysis of modifications in the key functions regulating glucose homeostasis in ruminants.

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Insulin secretion and substrate homeostasis in prolonged hypothermia in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.255.6.r1035 ◽

1988 ◽

Vol 255 (6) ◽

pp. R1035-R1040

Author(s):

R. Hoo-Paris ◽

M. L. Jourdan ◽

L. C. Wang ◽

R. Rajotte

Keyword(s):

Insulin Secretion ◽

Plasma Glucose ◽

Low Temperatures ◽

Plasma Insulin ◽

Glucose Utilization ◽

Exogenous Insulin ◽

Metabolic Substrate ◽

Endogenous Insulin ◽

Dose Dependent Decrease ◽

Dose Dependent

In hypothermia, impairment of metabolic substrate mobilization and utilization may be a factor limiting survival. By use of a newly developed technique, substrate profiles and their regulation by insulin were examined in hypothermic rats (body temperature 19 degrees C) over 24 h. Plasma glucose concentrations increased to approximately 300 mg/dl during cooling and remained high throughout the period of hypothermia. Free fatty acid (FFA) concentration was not altered during cooling or during the first 10 h of hypothermia (approximately 700 mu eq/l) but progressively decreased thereafter, reaching 420 mu eq/l by 20 h. Plasma insulin decreased dramatically during cooling and remained very low (9 +/- 2 microU/ml) during the whole period of hypothermia, reflecting the suppression of insulin secretion by isolated islets at low temperatures. To test he hypothesis that suppression of endogenous insulin secretion may hamper glucose utilization and thus limit survival in hypothermia, exogenous insulin was administered. At doses of 0.1, 0.5, and 1 U/kg intravenously, insulin slowly decreased plasma glucose and FFA. However, at 0.1 and 1 U/kg intraperitoneally, insulin resulted in a dose-dependent decrease in survival time in the hypothermic rat. It is possible that the antilipolytic effect of insulin may have outweighed any beneficial effect of improving glucose utilization in hypothermia.

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Increased insulin sensitivity and responsiveness during lactation in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.251.5.e537 ◽

1986 ◽

Vol 251 (5) ◽

pp. E537-E541 ◽

Cited By ~ 8

Author(s):

A. F. Burnol ◽

A. Leturque ◽

P. Ferre ◽

J. Kande ◽

J. Girard

Keyword(s):

Insulin Sensitivity ◽

Plasma Insulin ◽

Glucose Utilization ◽

Glucose Production ◽

Utilization Rate ◽

Glucose Turnover ◽

Metabolic Clearance ◽

Maximal Effect ◽

Euglycemic Hyperinsulinemic Clamp ◽

Peripheral Tissues

In 12-day lactating rats blood glucose and plasma insulin were decreased by, respectively, 20 and 35% when compared with nonlactating rats, despite a 25% increase of their glucose turnover rate. Then, by using the euglycemic hyperinsulinemic clamp technique, dose-response curves for the effects of insulin on glucose production and utilization in lactating and nonlactating rats were performed. Glucose production rate was totally suppressed at 250 microU/ml of insulin in lactating rats and for plasma insulin concentrations higher than 500 microU/ml in nonlactating rats. Plasma insulin level inducing half-maximal inhibition of glucose production was decreased by 60% during lactation. The maximal effect of insulin on glucose utilization rate and glucose metabolic clearance rate was, respectively, increased 1.5- and 2.4-fold during lactation and was obtained for plasma insulin concentrations lower in lactating than in nonlactating rats (250 vs. 500 microU/ml). Insulin concentrations inducing half-maximal stimulation of glucose utilization and glucose metabolic clearance were decreased by 50% during lactation. In conclusion, this study has shown that insulin sensitivity and responsiveness of liver and peripheral tissues are improved at peak lactation in the rat.

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In vivo insulin secretion and action in hyperglycemic rat

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1989.257.2.e180 ◽

1989 ◽

Vol 257 (2) ◽

pp. E180-E184 ◽

Cited By ~ 3

Author(s):

M. C. Laury ◽

L. Penicaud ◽

A. Ktorza ◽

H. Benhaiem ◽

M. T. Bihoreau ◽

...

Keyword(s):

Insulin Secretion ◽

Plasma Insulin ◽

Glucose Utilization ◽

Insulin Level ◽

Glucose Infusion ◽

Short Term ◽

Glucose Ratio ◽

Tissue Sensitivity ◽

Infusion Period

This work was designed to study the effects of insulin secretion and action in vivo of moderate hyperglycemia induced by glucose infusion during 4 days in unrestrained rats. The maintenance of a glycemia around 170 mg/dl throughout the infusion time necessitated a gradual increase of glucose infusion rate from 11.5 to 19 g/day. Throughout the infusion period, plasma insulin-to-glucose ratio remained much higher in hyperglycemic rats (HG) than in controls. Glucose tolerance and insulin secretion tests were performed 2 h after the end of the infusion, when glycemia and insulinemia were back to basal values. Incremental plasma glucose values were significantly lower in HG than in control rats without significant changes in incremental plasma insulin concentrations, suggesting an increased insulin efficiency. At the same insulin level, glucose utilization was higher in HG than in control rats during euglycemic-hyperinsulinemic clamps. These data show that short-term hyperglycemia and hyperinsulinemia do not induce a defect in insulin secretion in vivo and do increase tissue sensitivity to insulin.

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Effect of insulin on in vivo glucose utilization in individual tissues of anesthetized lactating rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1987.252.2.e183 ◽

1987 ◽

Vol 252 (2) ◽

pp. E183-E188 ◽

Cited By ~ 7

Author(s):

A. F. Burnol ◽

P. Ferre ◽

A. Leturque ◽

J. Girard

Keyword(s):

Adipose Tissue ◽

Mammary Gland ◽

White Adipose Tissue ◽

Skeletal Muscles ◽

Plasma Insulin ◽

Glucose Utilization ◽

Insulin Concentration ◽

Utilization Rate ◽

Plasma Insulin Concentration ◽

Euglycemic Hyperinsulinemic Clamp

Glucose utilization rate has been measured in skeletal muscles, white adipose tissue, and mammary gland of anesthetized nonlactating and lactating rats. During lactation, basal glucose utilization is decreased by 40% in periovarian white adipose tissue and by 65% in epitrochlearis and extensor digitorum longus but not in soleus muscle. This may be related to the lower blood glucose and plasma insulin concentrations observed during lactation. Basal glucose utilization rate in the mammary gland was, respectively, 18 +/- 2 and 350 +/- 50 micrograms/min in nonlactating and lactating rats. During the euglycemic hyperinsulinemic clamp, a physiological increment in plasma insulin concentration (231 +/- 18 in lactating vs. 306 +/- 24 microU/ml in nonlactating rats) induces a similar increase in glucose utilization rate in skeletal muscles (except soleus) and white adipose tissue in the two groups of rats. Furthermore this low increase in plasma insulin concentration does not alter mammary glucose utilization rate in nonlactating rats but induces the same increase (sevenfold over basal) as a maximal insulin concentration in lactating rats. These data show that the active mammary gland is the most insulin-sensitive tissue of the lactating rat that has been tested. The overall increase in insulin sensitivity and responsiveness that has been described in lactating rats can then mainly be attributed to the presence of the active mammary gland.

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SPONTANEOUS HYPOGLYCAEMIA AND SARCOMA

Acta Endocrinologica ◽

10.1530/acta.0.0500233 ◽

1965 ◽

Vol 50 (2) ◽

pp. 233-238 ◽

Cited By ~ 6

Author(s):

J. A. R. Friend ◽

C. N. Hales

Keyword(s):

Insulin Secretion ◽

Plasma Insulin ◽

Slow Growing ◽

Insulin Like Activity

ABSTRACT A patient with a slow-growing fibrosarcoma of ovarian origin developed attacks of hypoglycaemia. Estimations of plasma insulin-like activity and immunoassay of plasma insulin under a variety of conditions showed no evidence of abnormal insulin secretion. In addition, the responses to glucagon, tolbutamide, and L-leucine showed no definite abnormality. Possible mechanisms for the occurrence of the hypoglycaemia are discussed.

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A Technique to Determine Unsteady-State Inhibition Kinetics in the Activated Sludge Process

Water Science & Technology ◽

10.2166/wst.1989.0261 ◽

1989 ◽

Vol 21 (6-7) ◽

pp. 593-602 ◽

Cited By ~ 3

Author(s):

Andrew T. Watkin ◽

W. Wesley Eckenfelder

Keyword(s):

Activated Sludge ◽

Kinetic Parameters ◽

Curve Fitting ◽

Glucose Utilization ◽

Batch Reactor ◽

Synthetic Data ◽

Utilization Rate ◽

Fitting Algorithm ◽

Test Reactor ◽

Two Parameter

A technique for rapidly determining Monod and inhibition kinetic parameters in activated sludge is evaluated. The method studied is known as the fed-batch reactor technique and requires approximately three hours to complete. The technique allows for a gradual build-up of substrate in the test reactor by introducing the substrate at a feed rate greater than the maximum substrate utilization rate. Both inhibitory and non-inhibitory substrate responses are modeled using a nonlinear numerical curve-fitting technique. The responses of both glucose and 2,4-dichlorophenol (DCP) are studied using activated sludges with various acclimation histories. Statistically different inhibition constants, KI, for DCP inhibition of glucose utilization were found for the various sludges studied. The curve-fitting algorithm was verified in its ability to accurately retrieve two kinetic parameters from synthetic data generated by superimposing normally distributed random error onto the two parameter numerical solution generated by the algorithm.

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GLUT2 and hexokinase control proximodistal gradient of intestinal glucose metabolism in the newborn pig

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1997.272.6.g1530 ◽

1997 ◽

Vol 272 (6) ◽

pp. G1530-G1539 ◽

Cited By ~ 2

Author(s):

C. Cherbuy ◽

B. Darcy-Vrillon ◽

L. Posho ◽

P. Vaugelade ◽

M. T. Morel ◽

...

Keyword(s):

Glucose Metabolism ◽

Glucose Transporter ◽

Glucose Utilization ◽

Specific Effect ◽

Glucose Consumption ◽

Utilization Rate ◽

Glucose Turnover ◽

Proximal Jejunum ◽

A Site

We have reported previously that a high glycolytic capacity develops soon after birth in enterocytes isolated from suckling newborn pigs. In the present work, we investigated whether such metabolic changes could affect intestinal glucose utilization in vivo and examined possible variations in glucose metabolism along the small intestine. Glucose utilization by individual tissues was assessed using the 2-deoxyglucose technique. The overall glucose utilization rate was doubled in suckling vs. fasting 2-day-old pigs because of significantly higher rates in all tissues studied, except for the brain. In parallel, enterocytes were isolated from the proximal, medium, or distal jejunoileum of newborn vs. 2-day-old pigs and assessed for their capacity to utilize, transport, and phosphorylate glucose. Intestinal glucose consumption accounted for approximately 15% of glucose turnover rate in suckling vs. 8% in fasting pigs. Moreover, there was a proximal-to-distal gradient of glucose utilization in the intestinal mucosa of suckling pigs. Such a gradient was also evidenced on isolated enterocytes. The stimulation of both hexokinase activity (HK2 isoform) and basolateral glucose transporter (GLUT2), as observed in the proximal jejunum, could account for such a site-specific effect of suckling.

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Relationship of Insulin Secretion Rate to Blood Glucose Concentration in Newborn and Adult Dogs

Neonatology ◽

10.1159/000240184 ◽

1969 ◽

Vol 14 (3-4) ◽

pp. 194-202 ◽

Cited By ~ 4

Author(s):

P.A.J. Adam ◽

D. Kornhauser ◽

D. Link ◽

R. Schwartz

Keyword(s):

Insulin Secretion ◽

Blood Glucose ◽

Glucose Concentration ◽

Blood Glucose Concentration ◽

Secretion Rate ◽

Relationship Of ◽

Insulin Secretion Rate

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Insulin secretion, body composition and pig performance are altered by feeding pattern

Animal Production Science ◽

10.1071/an13120 ◽

2014 ◽

Vol 54 (3) ◽

pp. 319 ◽

Cited By ~ 5

Author(s):

Ronald E. Newman ◽

Jeffery A. Downing ◽

Peter C. Thomson ◽

Cherie L. Collins ◽

David J. Henman ◽

...

Keyword(s):

Insulin Secretion ◽

Feed Intake ◽

Plasma Insulin ◽

Feeding Strategy ◽

Growing Pigs ◽

Carcass Composition ◽

Production Performance ◽

Feed Conversion ◽

Ad Libitum ◽

Entire Male

Three studies investigated the effect of feeding strategy on production performance and endocrine status of growing pigs. For Experiment 1, 20 entire male pigs (70.0 ± 4.6 kg) were allocated randomly to individual pens in one of four climate-controlled rooms. Pigs were fed for 23 days either ad libitum or entrained to feed bi-phasically for two 90-min periods. For Experiment 2, 20 entire male pigs (41.2 ± 3.5 kg) were housed as per Experiment 1. Pigs were fed for 49 days either ad libitum or fed bi-phasically for two 60-min periods. For Experiment 3, 100 female pigs (66.1 ± 3.5 kg) were randomly allocated to individual pens within a commercial piggery and fed for 42 days either ad libitum or bi-phasically for two 60-min periods. Ear vein catheters were inserted into 10 pigs from each group and hourly blood samples were collected for 24 h in Experiments 1 and 2 and for 11 h in Experiment 3. Plasma insulin, non-esterified fatty acid and glucose concentrations were determined in Experiments 1 and 2, and glucose and insulin concentrations in Experiment 3. Feed intake and performance were recorded in all experiments and carcass composition was assessed by computed tomography for Experiment 2. There were no differences in final liveweight between the two treatment groups for all experiments. Pigs fed for two 90-min periods (Experiment 1) showed no difference in feed intake when compared with feeding ad libitum. Pigs in Experiment 2 fed for two 60-min intervals consumed 2.49 kg/pig.day compared with those fed ad libitum that consumed 2.68 kg/day (P = 0.057). In Experiment 3, pigs fed twice daily consumed 2.82 kg/pig.day compared with 2.91 kg/pig.day in ad libitum-fed pigs (P = 0.051). Bi-phasic fed pigs in Experiment 2 had improved (P < 0.05) feed conversion efficiency compared with pigs fed ad libitum. For all experiments, there was no difference in plasma glucose concentrations between the two treatments. In all three experiments, the circulating insulin concentrations for pigs fed ad libitum remained at a constant level throughout the sampling period. However, plasma insulin concentrations for the bi-phasic fed pigs significantly increased ~1 h after both feeding periods during all three experiments. Insulin secretion of pigs fed for two 90-min periods differed from that of pigs fed for two 60-min periods. Plasma insulin concentration increased five-fold following feeding for 60 min, compared with that in pigs fed for 90 min, which increased two-fold. Bi-phasic-fed pigs from Experiment 2 had reduced (P < 0.05) total carcass fat and significantly increased muscle when compared with pigs fed ad libitum. The data showed that feeding pigs at two succinct periods aligned insulin secretion to the time of feeding. Pigs fed for 60 min, unlike those fed for 90-min intervals, had reduced feed intake in comparison to those fed ad libitum. This may suggest that the duration of the feeding bout is important for this response and this may in turn influence both energy balance and the way energy is partitioned.

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