Physiological increments in plasma insulin concentrations have selective and different effects on synthesis of hepatic proteins in normal humans

The relationship between the rate of lipolysis and rate of glucose production (Ra) was investigated in 14- and 86-h fasted humans. [6,6-2H]glucose and [2H]5glycerol were infused to measure glucose and glycerol Ra in response to infusions of nicotinic acid in 14- and 86-h fasted subjects (protocol 1). The response of glucose Ra to nicotinic acid alone and nicotinic acid plus unlabeled glycerol was also measured in 86-h fasted subjects (protocol 2). After a 14-h fast, nicotinic acid caused a 30% decrease in plasma insulin levels and a marked (66%) decrease in plasma free fatty acid levels but did not have any significant effect on glucose Ra and concentration. After 86 h of fasting, nicotinic acid decreased glycerol Ra and hence lipolytic rate by approximately 60%. This caused a significant decrease (P less than 0.05) of 16-20% in glucose Ra and uptake. This decrease in glucose Ra was abolished when unlabeled glycerol was also infused with nicotinic acid to maintain glycerol Ra. These findings suggest that, in normal humans, a decrease in the rate of lipolysis regulates glucose Ra via its effect on the availability of glycerol for gluconeogenesis.

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Role of gluconeogenesis in epinephrine-stimulated hepatic glucose production in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1983.245.3.e294 ◽

1983 ◽

Vol 245 (3) ◽

pp. E294-E302 ◽

Cited By ~ 17

Author(s):

L. Sacca ◽

C. Vigorito ◽

M. Cicala ◽

G. Corso ◽

R. S. Sherwin

Keyword(s):

Plasma Insulin ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Base Line ◽

Epinephrine Infusion ◽

Hepatic Glucose ◽

Normal Humans ◽

Glucose Output ◽

Sustained Increase

To evaluate the contribution of gluconeogenesis to epinephrine-stimulated glucose production, we infused epinephrine (0.06 micrograms X kg-1 X min-1) for 90 min into normal humans during combined hepatic vein catheterization and [U-14C]alanine infusion. Epinephrine infusion produced a rise in blood glucose (50-60%) and plasma insulin (30-40%), whereas glucagon levels increased only at 30 min (19%, P less than 0.05). Net splanchnic glucose output transiently increased by 150% and then returned to base line by 60 min. In contrast, the conversion of labeled alanine and lactate into glucose increased fourfold and remained elevated throughout the epinephrine infusion. Similarly, epinephrine produced a sustained increase in the net splanchnic uptake of cold lactate (four- to fivefold) and alanine (50-80%) although the fractional extraction of both substrates by splanchnic tissues was unchanged. We conclude that a) epinephrine is a potent stimulator of gluconeogenesis in humans, and b) this effect is primarily mediated by mobilization of lactate and alanine from extrasplanchnic tissues. Our data suggest that the initial epinephrine-induced rise in glucose production is largely due to activation of glycogenolysis. Thereafter, the effect of epinephrine on glycogenolysis (but not gluconeogenesis) wanes, and epinephrine-stimulated gluconeogenesis becomes the major factor maintaining hepatic glucose production.

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Metformin Decreases the High Plasminogen Activator Inhibition Capacity, Plasma Insulin and Triglyceride Levels in Non-Diabetic Obese Subjects

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651126 ◽

1987 ◽

Vol 57 (03) ◽

pp. 326-328 ◽

Cited By ~ 118

Author(s):

Ph Vague ◽

I Juhan-Vague ◽

M C Alessi ◽

C Badier ◽

J Valadier

Keyword(s):

Plasminogen Activator ◽

Fibrinolytic Activity ◽

Plasma Insulin ◽

Normal Glucose Tolerance ◽

Double Blind Study ◽

Obese Women ◽

Double Blind ◽

Normal Glucose ◽

Plasma Insulin Levels ◽

Obese Subjects

SummaryWe have previously observed a positive correlation between Plasminogen Activator Inhibition capacity (PA Inhibition), Body Mass Index (BMI) and plasma insulin levels in a population of non diabetic subjects. The anti diabetic biguanide Metformin which decreases insulin resistance has been reported to increase the blood fibrinolytic activity. Therefore we have studied the effect of Metformin on PA Inhibition levels in obese subjects with normal glucose tolerance. Eighteen obese women (O) (BMI: 31.4 ± 1.13, m ± S.E.M.) were compared to age matched controls (C) (BMI: 20.2 ± 0.8) and randomized to a 15 days treatment by Metformin (M) (1.7 g/day) or placebo (P) in a double blind study while on a weight maintaining diet. O compared to C had higher levels (m ± S.E.M.) of PA Inhibition (9 ± 1.8 IU/ml, versus 2.88 ± 0.29 p <0.01), lower euglobulin fibrinolytic activity (EFA) (4.95 ±1.17 mm versus 9 ± 0.29 p <0.05), higher plasma insulin (24.1 ±2.1. uU/ml), versus 12 ± 1 p <0.01) and triglyceride (1.32 ± 0.16 mmol/1, versus 0.8 ± 0.08 p <0.05). After 15 days of treatment, in group M a significant decrease in PA Inhibition (5.51 ± 1.4, versus 9.48 ±2.1 p <0.05) in plasma insulin (18.5 ±0.1, versus 24.5 ± 3.5, p <0.05) and plasma triglyceride (1.08 ± 0.1, versus 1.47 ± 0.3 p <0.05) and an increase in EFA (6.50 ± 0.28, versus 5.25 ± 0.35 p <0.05) were observed. No significant variation was observed in group P.

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Determinants of Plasminogen Activator Inhibitor-1 Activity in Survivors of Myocardial Infarction

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653762 ◽

1995 ◽

Vol 73 (02) ◽

pp. 261-267 ◽

Cited By ~ 19

Author(s):

Rosaire P Gray ◽

Vidya Mohamed-Ali ◽

David L H Patterson ◽

John S Yudkin

Keyword(s):

Myocardial Infarction ◽

Plasminogen Activator ◽

Plasma Insulin ◽

Plasminogen Activator Inhibitor ◽

Immunoreactive Insulin ◽

Plasminogen Activator Inhibitor 1 ◽

Serum Triglycerides ◽

Fasting Plasma ◽

Activator Inhibitor ◽

Pai 1

SummaryA significant relationship has been described between plasminogen activator inhibitor-1 (PAI-1) and plasma insulin concentrations. However, most radioimmunoassays (RIA) substantially overestimate plasma insulin concentrations because of cross reaction with proinsulin-like molecules and it has been proposed that proinsulin-like molecules may be important determinants of PAI-1 activity. We measured fasting plasma immunoreactive insulin by conventional RIA, fasting plasma insulin (EIMA) by specific two site immuno-enzymometric assay, and intact proinsulin and des-31,32-proinsulin by two site immunoradiometric assay (IRMA) in 74 (50 nondiabetic and 24 diabetic) subjects who had survived a myocardial infarction between 6 and 24 months previously. In univariate analysis, PAI-1 activity correlated with serum triglycerides (rs=0.43; p <0.0001), insulin sensitivity (rs = -0.30; p = 0.004), and immunoreactive insulin (rs = 0.45; p <0.0001). However, the relationship between PAI-1 activity and plasma specific insulin (IEMA) was weaker (rs = 0.24; p = 0.019) than those with intact proinsulin (rs = 0.53; p <0.0001) and des-31,32-proinsulin (rs = 0.54; p <0.0001) despite the low concentrations of these proinsulin-like molecules. In multiple regression analysis, only des-31,32-proinsulin (p = 0.001) and serum triglycerides (p = 0.013) were significant determinants of PAI-1 activity. In conclusion, these results suggest that proinsulin-like molecules and serum triglycerides are important determinants of PAI-1 activity in survivors of myocardial infarction.

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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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THERAPIE EINES METASTASIERENDEN INSELZELLTUMORS MIT STREPTOZOTOCIN

Acta Endocrinologica ◽

10.1530/acta.0.0670405 ◽

1971 ◽

Vol 67 (2) ◽

pp. 405-416 ◽

Cited By ~ 8

Author(s):

E. Nieschlag ◽

H. Wombacher ◽

F. J. Kroeger ◽

L.V. Habighorst

Keyword(s):

Liver Metastases ◽

Blood Sugar ◽

Mechanism Of Action ◽

Islet Cell ◽

Plasma Insulin ◽

Severe Hypoglycaemia ◽

Islet Cells ◽

Intravenous Injections ◽

High Affinity ◽

Methyl Nitrosourea

A patient with a metastazing functional islet cell tumour suffering from severe hypoglycaemia was treated with streptozotocin. Four intravenous injections of 1.5 g streptozotocin each were administered in 4 to 6 days intervals. After the 4th injection there were no further episodes of hypoglycaemia, parenteral glucose administration could be stopped and blood sugar and plasma insulin, showing concentrations of up to 405 μU/ml before treatment, reached normal levels. The tumours in the pancreas disappeared and the liver metastases decreased in size and number as judged by arteriography. A hypothesis for the mechanism of action of streptozotocin is proposed. The glucose moiety is considered to facilitate a high affinity to the islet cells whereas the N-methyl-nitrosourea residue serves the active antitumour part of the molecule.

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THE EFFECT OF THE PROGESTOGEN ETHYNODIOL DIACETATE ON GLUCOSE, INSULIN, AND GROWTH HORMONE AFTER SIX MONTHS TREATMENT

Acta Endocrinologica ◽

10.1530/acta.0.0700373 ◽

1972 ◽

Vol 70 (2) ◽

pp. 373-384 ◽

Cited By ~ 22

Author(s):

W. N. Spellacy ◽

W. C. Buhi ◽

S. A. Birk

Keyword(s):

Growth Hormone ◽

Blood Glucose ◽

Plasma Insulin ◽

Tolerance Test ◽

Metabolic Effects ◽

Oral Glucose ◽

Hormone Levels ◽

Glucose Levels ◽

Ethynodiol Diacetate ◽

Tolerance Curve

ABSTRACT Seventy-one women were treated with a daily dose of 0.25 mg of the progestogen ethynodiol diacetate. They were all tested with a three-hour oral glucose tolerance test before beginning the steroid and then again during the sixth month of use. Measurements were made of blood glucose and plasma insulin and growth hormone levels. There was a significant elevation of the blood glucose levels after steroid treatment as well as a deterioration in the tolerance curve in 12.9% of the women. The plasma insulin values were also elevated after drug treatment whereas the fasting ambulatory growth hormone levels did not significantly change. There was a significant association between the changes in glucose and insulin levels and the subject's age, control weight, or weight gain during treatment. The importance of considering the metabolic effects of the progestogen component of oral contraceptives is stressed.

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STUDIES ON SULFATION FACTOR (SF) ACTIVITY OF HUMAN SERUM

Acta Endocrinologica ◽

10.1530/acta.0.xxxv0381 ◽

1960 ◽

Vol XXXV (III) ◽

pp. 381-396 ◽

Cited By ~ 14

Author(s):

Sven Almqvist

Keyword(s):

Human Serum ◽

Normal Serum ◽

Treatment Level ◽

Response Curves ◽

Normal Children ◽

Significant Difference ◽

Human Sera ◽

Normal Humans ◽

Pre Treatment ◽

Dose Levels

ABSTRACT The sulfation factor (SF) activity of human sera has been estimated using a modification of the method of Daughaday et al. (1959). Each assay was statistically evaluated. The method had a mean precision of 0.14 and, used as an assay of GH of human serum, a sensitivity in three pituitary dwarfs of 0.1 to 0.6 μg of HGH/ml of serum. SF activity was found at all ages between 1 month and 75 years. There was a significantly lower mean SF activity below the age of half a year. Three cases of pituitary dwarfism had significantly low SF activities of sera. There was no significant difference between the SF activities of sera from untreated pituitary dwarfs and the sera from normal children below half a year of age. Dose-response curves with large volumes of sera from pituitary dwarfs and small volumes of sera from normal humans had the same slopes. Four mg of HGH prepared according to the method of Li & Papkoff (1956) resulted in a normal serum SF activity in each of the three dwarfs. A significant (P < 0.01) linear relationship was found between the concentration of SF activity of sera from these subjects and the logarithm of the dose of HGH given with dose levels of 1, 2 and 4 mg daily for three days. The decline of serum SF activity to the pre-treatment level following HGH in one dwarf suggested a half life not different from that indicated by others for growth hormone.

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