Insulin resistance in acromegaly: defects in both hepatic and extrahepatic insulin action

1986 ◽  
Vol 250 (3) ◽  
pp. E269-E273 ◽  
Author(s):  
I. Hansen ◽  
E. Tsalikian ◽  
B. Beaufrere ◽  
J. Gerich ◽  
M. Haymond ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Insulin Action ◽  
Glucose Utilization ◽  
Insulin Dose ◽  
Glucose Production ◽  
Insulin Binding ◽  
Response Curves ◽  
Control Subjects ◽  
Normal Monocyte ◽  
Stimulation Of

Short-term growth hormone excess is associated with impaired hepatic and extrahepatic responses to insulin in the absence of a change in insulin binding. To determine whether similar defects occur after chronic growth hormone excess, insulin dose-response curves for stimulation of glucose utilization and suppression of glucose production and monocyte and erythrocyte insulin binding were determined in five acromegalic patients and six healthy volunteers of comparable age, sex, and obesity. During infusion of insulin, glucose infusion rates required to maintain euglycemia were significantly lower (P less than 0.02 all) in the acromegalic patients than in the control subjects. Suppression of glucose production was impaired in the acromegalic subjects at insulin concentrations in the physiological range but not at insulin concentrations in the supraphysiological range. In contrast stimulation of glucose utilization was decreased in the acromegalic subjects at both physiological and supraphysiological insulin concentrations. Neither monocyte nor erythrocyte insulin binding differed significantly in the acromegalic and control subjects. These data indicate that chronic growth hormone excess is associated with a defect in both hepatic and extrahepatic insulin action. The decrease in glucose utilization at supraphysiological insulin concentrations in the acromegalic subjects and the normal monocyte and erythrocyte insulin binding suggest a postbinding alteration in insulin action.

scholarly journals Biosynthesis of growth hormone in the rat anterior pituitary gland. Stimulation of biosynthesis in vitro by insulin

1973 ◽  
Vol 134 (4) ◽  
pp. 1103-1113 ◽  
Author(s):  
A. Betteridge ◽  
M. Wallis
Keyword(s):  
Growth Hormone ◽  
Anterior Pituitary ◽  
Rna Synthesis ◽  
Glucose Utilization ◽  
Actinomycin D ◽  
Hormone Synthesis ◽  
Pituitary Glands ◽  
Hormone Biosynthesis ◽  
Stimulation Of

The effect of insulin on the incorporation of radioactive leucine into growth hormone was investigated by using rat anterior pituitary glands incubated in vitro. A 50% stimulation over control values was observed at insulin concentrations above 2μm (280munits/ml). The effect was specific for growth hormone biosynthesis, over the range 1–5μm-insulin (140–700munits/ml). Lower more physiological concentrations had no significant effect in this system. Above 10μm (1.4 units/ml) total protein synthesis was also increased. The stimulation of growth hormone synthesis could be partially blocked by the addition of actinomycin D, suggesting that RNA synthesis was involved. Insulin was found to stimulate the rate of glucose utilization in a similar way to growth hormone synthesis. 2-Deoxyglucose and phloridzin, which both prevented insulin from stimulating glucose utilization, also prevented the effect of insulin on growth hormone synthesis. If glucose was replaced by fructose in the medium, the effect of insulin on growth hormone synthesis was decreased. We conclude that the rate of utilization of glucose may be an important step in mediating the effect of insulin on growth hormone synthesis.

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.

Hepatic glucose production and insulin sensitivity and responsiveness in iron-deficient anemic rats

1993 ◽  
Vol 264 (3) ◽  
pp. E380-E390 ◽  
Author(s):  
M. J. Borel ◽  
J. L. Beard ◽  
P. A. Farrell
Keyword(s):  
Insulin Sensitivity ◽  
Hepatic Glucose Production ◽  
Insulin Dose ◽  
Glucose Production ◽  
Deficiency Anemia ◽  
Response Curves ◽  
Iron Deficient ◽  
Hepatic Glucose ◽  
Basal Plasma ◽  
Insulin Responsiveness

We performed euglycemic hyperinsulinemic glucose clamps at insulin infusion rates of 1.9, 4.0, 9.3, and 19.3 mU.kg-1 x min-1 in rats with varying severities of iron deficiency anemia (IDA; mean hemoglobin concentrations of 59, 79, 107, and 137 g/l) to assess the effect of IDA on insulin sensitivity and responsiveness. Glucose appearance and disappearance (Rd) rates were determined using a primed continuous infusion of [3-3H]glucose. Basal plasma glucose and insulin concentrations were similar between the IDA and control rats. Basal hepatic glucose production was significantly (P = 0.0001) elevated in the two most anemic groups (13.6 +/- 2.4 and 12.6 +/- 3.1 vs. 10.6 +/- 2.2 and 10.2 +/- 2.0 mg.kg-1 x min-1). A significant upward shift in the insulin dose-response curves for Rd indicated an increase in peripheral insulin responsiveness in the two most anemic groups while a slight leftward shift was suggestive of an increase in insulin sensitivity in all three anemic groups. Hepatic insulin sensitivity and responsiveness were unaffected by IDA. We conclude that increased glucose utilization rates in IDA rats are due primarily to an increase in peripheral insulin responsiveness.

EVALUATION OF PROPRANOLOL-GLUCAGON TEST

1977 ◽  
Vol 86 (2) ◽  
pp. 243-250 ◽  
Author(s):  
Y. Okada ◽  
K. Watanabe ◽  
T. Takeuchi ◽  
T. Hata ◽  
H. Mikam ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
False Negative ◽  
Human Growth ◽  
Maximum Level ◽  
Normal Children ◽  
Provocative Test ◽  
Glucagon Test ◽  
Control Subjects ◽  
Stimulation Of

ABSTRACT A propranolol-glucagon test was evaluated in 24 control normal children, 21 pituitary dwarfs, 15 patients with constitutional short stature, 2 with chromosome aberration and 4 with miscellaneous diseases. The dose of glucagon enough for the stimulation of human growth hormone (HGH) secretion is more than 20 μg/kg of body weight. During the test in the control subjects the serum HGH level increased from 2.3 ± 1.2 ng/ml to a maximum level of 30.0 ± 15.1 ng/ml, when 10 mg propranolol, regardless of body weight and 30 μg glucagon per kg of body weight are given. The dose of propranolol administered ranged from 0.2 to 1.0 mg/kg of body weight in normal children studied. Serum 11-OHCS also increased significantly from 14.5 ± 11.2 μg/100 ml to 30.1 ± 15.5 μg/100 ml (P <0.01). There was no difference in the maximum level of urinary total catecholamines in propranolol-glucagon test between 7 pituitary dwarfs and 7 control subjects. The mechanism of HGH response to propranolol-glucagon administration is unknown, but propranolol-glucagon administration is a sensitive and reliable provocative test for HGH secretion, since false negative responses of HGH are not observed in patients with non-pituitary disease.

Insulin secretion and action and the response of endogenous glucose production to a lack of glucagon suppression in non-diabetic subjects

2021 ◽  
Author(s):  
Jon D Adams ◽  
Aoife M Egan ◽  
Marcello C Laurenti ◽  
Daniel J Schembri Wismayer ◽  
Kent R Bailey ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Action ◽  
Insulin Dose ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Oral Glucose ◽  
Prandial Insulin ◽  
Anthropometric Characteristics ◽  
Glucagon Suppression ◽  
Endogenous Glucose

Type 2 diabetes is a disease characterized by impaired insulin secretion and defective glucagon suppression in the postprandial period. We examined the effect of impaired glucagon suppression on glucose concentrations and Endogenous Glucose Production (EGP) at different degrees of insulin secretory impairment. The contribution of anthropometric characteristics, peripheral, and hepatic insulin action to this variability was also examined. To do so, we studied 54 non-diabetic subjects on two occasions in which endogenous hormone secretion was inhibited by somatostatin, with glucagon infused at a rate of 0.65 ng/kg/min, at 0 min to prevent a fall in glucagon (non-suppressed day) or at 120 min to create a transient fall in glucagon (suppressed day). Subjects received glucose (labeled with [3-3H]-glucose) infused to mimic the systemic appearance of 50g oral glucose. Insulin was infused to mimic a prandial insulin response in 18 subjects, another 18 received 80% of the dose and the remaining 18 received 60%. EGP was measured using the tracer-dilution technique. Decreased prandial insulin resulted in greater % increase in peak glucose but not in integrated glucose concentrations attributable to non-suppressed glucagon. The % change in integrated EGP was unaffected by insulin dose. Multivariate regression analysis, adjusted for age, sex, weight and insulin dose, did not show a relationship between the EGP response to impaired suppression of glucagon and insulin action as measured at the time of screening by oral glucose tolerance. A similar analysis for hepatic insulin action also did not show a relationship with the EGP response. These data indicate that the effect of impaired glucagon suppression on EGP is independent of anthropometric characteristics and insulin action.

Hepatic and extrahepatic insulin action in humans: measurement in the absence of non-steady-state error

1993 ◽  
Vol 264 (4) ◽  
pp. E561-E566 ◽  
Author(s):  
H. Katz ◽  
P. Butler ◽  
M. Homan ◽  
A. Zerman ◽  
A. Caumo ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Insulin Action ◽  
Insulin Dose ◽  
Glucose Turnover ◽  
Dilution Technique ◽  
Response Curves ◽  
Glucose Release ◽  
Hepatic Glucose ◽  
Nonsteady State ◽  
Hepatic Glucose Release

The isotope dilution technique has been extensively used to assess insulin action in humans. To determine if nonsteady state (NSS) has led to erroneous estimates of hepatic and extrahepatic insulin sensitivity, we measured glucose turnover in healthy subjects during infusion of insulin at rates of 0.25, 0.6, and 2.0 mU.kg-1.min-1. Turnover was calculated using Steele's traditional NSS equations [fixed-effective volume (pV) method] as well as with methods [radioactive infused glucose (hot-GINF) or variable pV] designed to minimize NSS error. In contrast to the fixed-pV method, both the hot-GINF and variable-pV methods indicated that several hours were required for suppression of hepatic glucose release at all insulin concentrations and that small increases in plasma insulin (approximately 100 pmol/l) had comparable effects on glucose disappearance and hepatic glucose release. Nevertheless, despite these differences, when turnover during the final hour of the insulin infusions was plotted vs. the prevailing insulin concentration, all three methods yielded similar insulin dose-response curves for suppression of hepatic glucose release. Thus despite previous errors in measurement of glucose turnover, the widely accepted belief that the human liver is exquisitely sensitive to small changes in insulin is correct.

Sign in / Sign up

Export Citation Format

Share Document