Glucose counterregulation during prolonged hypoglycemia in normal humans

1984 ◽  
Vol 247 (2) ◽  
pp. E206-E214 ◽  
Author(s):  
G. B. Bolli ◽  
I. S. Gottesman ◽  
P. E. Cryer ◽  
J. E. Gerich
Keyword(s):  
Insulin Secretion ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Regular Insulin ◽  
Glucose Turnover ◽  
Temporal Relationships ◽  
Human Volunteers ◽  
Clinical Disorders ◽  
Normal Humans ◽  
Normal Human

To study glucose counterregulation under conditions approximating those of clinical disorders in which hypoglycemia develops gradually and is reversed over a prolonged period, we injected regular insulin subcutaneously, in a dose (0.15 U/kg) selected to produce two- to threefold increases in plasma insulin, in 11 normal human volunteers and measured plasma glucose, insulin, C-peptide, and counterregulatory hormone concentrations as well as rates of glucose production, glucose utilization, and insulin secretion over 12 h. The data suggest that the mechanisms of gradual recovery from prolonged hypoglycemia may differ from those of rapid recovery from short-term hypoglycemia produced by intravenous injection of insulin in that 1) both stimulation of glucose production and limitation of glucose utilization contribute to recovery from prolonged hypoglycemia; 2) increases in glucagon, epinephrine, growth hormone, and cortisol secretion as well as a decrease in insulin secretion may all participate in glucose counterregulation during prolonged hypoglycemia; 3) epinephrine may play a more important role than glucagon during prolonged hypoglycemia. The latter two conclusions are based primarily on the temporal relationships between changes in the rates of glucose turnover and changes in plasma hormone concentrations and should not be considered proved. However, they provide the basis for testable hypotheses concerning the physiology of gradual recovery from prolonged hypoglycemia that can be expected to be relevant to the pathophysiology of clinical hypoglycemia.

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.

Diminution of insulin effect by growth hormone in hypophysectomized dogs; studies with C14 glucose

1959 ◽  
Vol 196 (2) ◽  
pp. 231-234 ◽  
Author(s):  
N. Altszuler ◽  
R. Steele ◽  
A. Dunn ◽  
J. S. Wall ◽  
R. C. de Bodo
Keyword(s):  
Growth Hormone ◽  
Intravenous Injection ◽  
Glucose Utilization ◽  
Normal Animal ◽  
Glucose Production ◽  
Insulin Injection ◽  
Glucose Turnover ◽  
Insulin Effect ◽  
Relationship Of ◽  
The Relationship

The mechanism whereby growth hormone diminishes the hypoglycemic effect of insulin was investigated in hypophysectomized dogs using a C14 glucose dilution technique. An intravenous injection of insulin into the normal dog increased the rate of glucose utilization, and the resulting hypoglycemia was promptly abolished by an increased rate of glucose production. In the hypophysectomized dog prior to growth hormone administration, the insulin injection increased the rate of glucose utilization to a greater extent than in the normal animal, while the ability to increase the rate of glucose production was shown to be limited. In the hypophysectomized dog, a growth hormone regimen (1 mg/kg/day for 4 days) increased the rate of glucose production and utilization. The intravenous injection of insulin during the growth hormone regimen resulted in a lesser increase in the rate of plasma glucose utilization than observed prior to the growth hormone regimen. Furthermore, the growth hormone regimen improved the animal's limited ability to increase glucose production in response to the insulin-induced hypoglycemia. These effects of growth hormone contribute to the decreased effectiveness of insulin. The relationship of the ‘anti-insulin’ effect of growth hormone to its influence on glucose turnover is discussed.

Effect of somatostatin on plasma glucagon and insulin, and glucose turnover in exercising sheep

1979 ◽  
Vol 47 (2) ◽  
pp. 273-278 ◽  
Author(s):  
R. P. Brockman
Keyword(s):  
Insulin Secretion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Strenuous Exercise ◽  
Glucose Turnover ◽  
Moderate Exercise ◽  
Plasma Glucagon ◽  
Hepatic Glucose ◽  
Exercise Induced ◽  
Glucagon And Insulin

To examine the roles of glucagon and insulin in exercise, four sheep were run on a treadmill with and without simultaneous infusion of somatostatin (SRIF), a peptide that suppresses glucagon and insulin secretion. SRIF infusion suppressed the exercise-induced rise in plasma glucagon during both moderate (5--5.5 km/h) and strenuous exercise (7.0 km/h). In addition, SRIF prevented the rise insulin concentrations during moderate exercise. During strenuous exercise, insulin concentrations were depressed in both groups. The infusion of SRIF was associated with a reduction in exercise-induced glucose production, as determined by infusion of [6–3H]glucose, during the first 15 min of both moderate and strenuous exercise compared to controls. Beyond 15 min glucose production was not significantly altered by SRIF infusions. These data are consistent with glucagon having an immediate, but only transient, stimulatory effect on the exercise-induced hepatic glucose production.

Effect of sequential infusions of glucagon and epinephrine on glucose turnover in the dog.

1978 ◽  
Vol 235 (3) ◽  
pp. E287 ◽  
Author(s):  
L Saccà ◽  
R Sherwin ◽  
P Felig
Keyword(s):  
Glucose Uptake ◽  
Plasma Glucose ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Conscious Dogs ◽  
Glucose Turnover ◽  
Plasma Glucagon ◽  
Conscious Dog ◽  
Glucose Clearance ◽  
Glucose Output

Conscious dogs were infused with 1) glucagon (3 ng/kg.min) alone for 120 min followed by glucagon plus epinephrine (0.1 microgram/kg.min) for 60 min and 2) epinephrine alone (150 min) followed by epinephrine plus glucagon for 90 min. Glucagon alone caused a 10--15 mg/dl rise in plasma glucose and a 45% increase in glucose production that returned to baseline by 75--120 min. After addition of epinephrine, glucose production rose again by 80%. Infusion of epinephrine alone resulted in unchanged plasma glucagon levels, a 60--70 mg/dl rise in plasma glucose, and an 80--100% rise in glucose production that returned to baseline by 60--120 min. When glucagon was added, glucose output promptly rose again by 85%. When glucagon was infused alone, there was a rise in glucose uptake, whereas, with epinephrine, glucose uptake failed to rise and glucose clearance fell by 35--50%. We conclude that 1) hepatic refractoriness to persistent elevations of glucagon or epinephrine is specific for the hormone infused; 2) epinephrine stimulates glucose production in the conscious dog in the absence of a rise in plasma glucagon; 3) the hyperglycemic response to glucagon or epinephrine is determined in part by accompanying changes in glucose utilization.

Increased insulin sensitivity and responsiveness during lactation in rats

1986 ◽  
Vol 251 (5) ◽  
pp. E537-E541 ◽  
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.

Glucose utilization and insulin action in adult rats submitted to prolonged food restriction

1992 ◽  
Vol 263 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
F. Escriva ◽  
C. Rodriguez ◽  
J. Cacho ◽  
C. Alvarez ◽  
B. Portha ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Insulin Action ◽  
Food Restriction ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Whole Body ◽  
Glucose Turnover ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Adult Rats ◽  
Peripheral Tissues

Glucose tolerance and insulin effects on glucose production and utilization by various tissues were studied in 70-day-old anesthetized rats submitted to food restriction from the fetal stage. Basal and glucose-induced plasma insulin levels were reduced in food-restricted rats without alterations in glucose tolerance. Insulin action was quantified by using the euglycemic-hyperinsulinemic clamp technique. Glucose turnover rates were measured by using D-[6-3H]glucose. Exogenous insulin failed to decrease glucose production in food-restricted rats. Weight-related whole body glucose utilization was higher in restricted rats than in controls both in the basal (21.9 +/- 0.7 vs. 9.4 +/- 0.6 mg.min-1.kg-1) and hyperinsulinemic states (37.5 +/- 1.1 vs. 14.0 +/- 1.2 mg.min-1.kg-1). Local glucose utilization by peripheral tissues was estimated by a 2-deoxy-D-[1-3H]glucose technique. In both basal and hyperinsulinemic conditions glucose utilization was increased in various adipose and muscle tissues of the food-restricted rats as compared with the controls. Thus we conclude that food restriction leads to an increase in the insulin-mediated glucose uptake by various peripheral tissues and to insulin resistance in the liver.

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 Low-dose IGF-I has no selective advantage over insulin in regulating glucose metabolism in hyperglycemic depancreatized dogs

2001 ◽  
Vol 168 (1) ◽  
pp. 49-58 ◽  
Author(s):  
SJ Fisher ◽  
ZQ Shi ◽  
HL Lickley ◽  
S Efendic ◽  
M Vranic ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Side Effects ◽  
Low Dose ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Selective Advantage ◽  
Metabolic Effects ◽  
High Dose ◽  
Differential Effects ◽  
Igf I

At supraphysiological levels, IGF-I bypasses some forms of insulin resistance and has been proposed as a therapeutic agent in the treatment of diabetes. Unfortunately, side effects of high-dose IGF-I (100-250 microg/kg) have precluded its clinical use. Low-dose IGF-I (40-80 microg/kg), however, shows minimal side effects but has not been systematically evaluated. In our previous study under conditions of declining glucose, low-dose IGF-I infusion was more effective in stimulating glucose utilization, but less effective in suppressing glucose production and lipolysis than low-dose insulin. However, under conditions of hyperglycemia, we could not observe any differential effects between high-dose infusions of IGF-I and insulin. To determine whether the differential effects of IGF-I and insulin are dose-related or related to the prevailing glucose level, 3 h glucose clamps were performed in the same animal model as in the previous studies, i.e. the moderately hyperglycemic (175 mg/dl) insulin-infused depancreatized dog, with additional infusions of low-dose IGF-I (67.8 microg/kg, i.e. 29.1 microg/kg bolus plus 0.215 microg/kg( )per min infusion; n=5) or insulin 49.5 mU/kg (9 mU/kg bolus plus 0.45 mU/kg per min; n=7). As in the previous study under conditions of declining glucose, low-dose IGF-I had significant metabolic effects in vivo, in our model of complete absence of endogenous insulin secretion. Glucose production was similarly suppressed with both IGF-I and insulin, by 54+/-3 and 56+/-2% s.e. (P=NS) respectively. Glucose utilization was stimulated to the same extent (IGF-I 5.2+/-0.2, insulin 5.5+/-0.3 mg/kg per min, P=NS). Glucagon, free fatty acid, glycerol, alanine and beta-hydroxybutyrate, were suppressed, while lactate and pyruvate levels were raised, similarly with IGF-I and insulin. We conclude that: (i) differential effects of IGF-I and insulin may be masked under hyperglycemic conditions, independent of the hormone dose; (ii) low-dose IGF-I has no selective advantage over additional insulin in suppressing glucose production and lipolysis, nor in stimulating glucose utilization during hyperglycemia and subbasal insulin infusion when insulin secretion is absent, as in type 1 diabetes mellitus.

Insulin resistance, but normal basal rates of glucose production in patients with newly diagnosed mild diabetes mellitus

1991 ◽  
Vol 124 (6) ◽  
pp. 637-645 ◽  
Author(s):  
Ole Hother-Nielsen ◽  
Henning Beck-Nielsen
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Glucose ◽  
Glucose Utilization ◽  
Ketone Bodies ◽  
Glucose Production ◽  
Glucose Turnover ◽  
Diabetic Patients ◽  
Newly Diagnosed ◽  
Turnover Rates ◽  
Mild Diabetes

Abstract. Fasting hyperglycemia in Type II (non-insulin-dependent) diabetes has been suggested to be due to hepatic overproduction of glucose and reduced glucose clearance. We studied 22 patients (10 lean and 12 obese) with newly diagnosed mild diabetes mellitus (fasting plasma glucose <15 mmol/l, urine ketone bodies <1 mmol/l), and two age- and weight-matched groups of non-diabetic control subjects. Glucose turnover rates and sensitivity to insulin were determined using adjusted primed-continuous [3-3H]glucose infusion and the hyperinsulinemic euglycemic clamp technique. Insulin-stimulated glucose utilization was reduced in both diabetic groups (lean patients: 313±35 vs 531±22 mg·m−2·min−1, p<0.01;obesepatients:311±28vs453±26mg·m−2·min−1, p<0.01). Basal plasma glucose concentrations decreased 0.43±0.05 mmol/l per h (p<0.01). Glucose production rates were smaller than glucose utilization rates (lean patients: 87±3 vs 94±3 mg·m−2·min−1, p<0.01; obese patients: 79±5 vs 88±5 mg·m−2 ·min−1, p<0.01), were not correlated to basal glucose or insulin concentrations, and were not different from normal (lean controls: 87±4 mg·−2·min−1; obese controls: 80±5 mg·m−2·min−1). These results suggest that the basal state in the diabetic patients is a compensated condition where glucose turnover rates are maintained near normal despite defects in insulin sensitivity.

Computer model for mechanisms underlying ultradian oscillations of insulin and glucose

1991 ◽  
Vol 260 (5) ◽  
pp. E801-E809 ◽  
Author(s):  
J. Sturis ◽  
K. S. Polonsky ◽  
E. Mosekilde ◽  
E. Van Cauter
Keyword(s):  
Insulin Secretion ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Feedback Loops ◽  
Oral Glucose ◽  
Negative Feedback Loops ◽  
Sustained Oscillations ◽  
Clinical Investigations ◽  
Glucose Ingestion ◽  
Experimental Findings

Oscillations in human insulin secretion have been observed in two distinct period ranges, 10-15 min (i.e. rapid) and 100-150 min (i.e., ultradian). The cause of the ultradian oscillations remains to be elucidated. To determine whether the oscillations could result from the feedback loops between insulin and glucose, a parsimonious mathematical model including the major mechanisms involved in glucose regulation was developed. This model comprises two major negative feedback loops describing the effects of insulin on glucose utilization and glucose production, respectively, and both loops include the stimulatory effect of glucose on insulin secretion. Model formulations and parameters are representative of results from published clinical investigations. The occurrence of sustained insulin and glucose oscillations was found to be dependent on two essential features: 1) a time delay of 30-45 min for the effect of insulin on glucose production and 2) a sluggish effect of insulin on glucose utilization, because insulin acts from a compartment remote from plasma. When these characteristics were incorporated in the model, numerical simulations mimicked all experimental findings so far observed for these ultradian oscillations, including 1) self-sustained oscillations during constant glucose infusion at various rates; 2) damped oscillations after meal or oral glucose ingestion; 3) increased amplitude of oscillation after increased stimulation of insulin secretion, without change in frequency; and 4) slight advance of the glucose oscillation compared with the insulin oscillation.(ABSTRACT TRUNCATED AT 250 WORDS)

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