Alleviation of Non-Islet Cell Tumour Hypoglycaemia by Growth Hormone Therapy is Associated with Changes in IGF Binding Protein-3

1992 ◽  
Vol 29 (3) ◽  
pp. 314-323 ◽  
Author(s):  
J D Teale ◽  
W F Blum ◽  
V Marks
Keyword(s):  
Growth Hormone ◽  
Islet Cell ◽  
Plasma Insulin ◽  
Specific Binding ◽  
Binding Protein ◽  
Insulin Response ◽  
Oral Glucose ◽  
Gh Treatment ◽  
Absolute Increase ◽  
Igfbp 3

The hypoglycaemia caused by non-islet cell tumours is often associated with an increase in plasma insulin-like activity. In many cases there is a relative if not always absolute increase in plasma insulin-like growth factor II (IGF-II). Growth hormone (GH) secretion is almost invariably depressed as is the plasma insulin response to oral glucose. Despite the high concentration of IGFs (i.e. IGF-I and IGF-II) normally found in the plasma of healthy people their potential hypoglycaemic effect is not manifest due to the tightness with which they are bound to specific binding proteins (IGFBPs). Plasma levels of the major binding protein (IGFBP-3), which is GH-dependent, were depressed in three patients with tumour induced hypoglycaemia. Treatment with biosynthetic GH restored IGFBP-3 to levels which were approximately equimolar to total plasma IGF concentrations, alleviated the hypoglycaemia and restored the plasma insulin responses to oral glucose. We suggest that after GH treatment IGF-II is sequestered by stimulated IGFBP-3 in association with a pre-existing acid-labile subunit to form high molecular weight complexes which prevent IGF-II gaining access to tissues receptors through which it exerts its hypoglycaemic effects.

PLASMA INSULIN RESPONSE DURING ORAL GLUCOSE TOLERANCE TESTS IN NEWBORNS OF NORMAL AND GESTATIONAL DIABETIC MOTHERS

PEDIATRICS ◽  
1969 ◽  
Vol 44 (1) ◽  
pp. 76-83
Author(s):  
Rosita S. Pildes ◽  
Robert J. Hart ◽  
Richard Warrner ◽  
Marvin Cornblath
Keyword(s):  
Growth Hormone ◽  
Blood Glucose ◽  
Plasma Insulin ◽  
Insulin Response ◽  
Sampling Interval ◽  
Oral Glucose ◽  
Glucose Tolerance Tests ◽  
Fasting Plasma Insulin ◽  
Insulin Responses ◽  
Diabetic Mothers

The plasma insulin, growth hormone, free fatty acids (FFA), and blood glucose responses to the oral ingestion of glucose were studied in eight infants of gestational diabetic mothers (IGDM) and in 11 normal newborns during the first 24 hours of life. Fasting blood sugars and growth hormone values were similar in the IGDM and the normal. Fasting plasma insulin values were significantly higher (14 ± 2 µU/ml) in the IGDM than those in the normal (7 ± 1 µU/ml), and FFA values were significantly lower (1268 ± 42 µEq/l versus 1627 ± 155 µEq/l). Blood glucose values at each sampling interval after the ingestion of glucose were significantly lower in the IGDM than those in the normal. Plasma insulin responses were prompt in the IGDM and delayed in the normal newborns; corresponding values at 30 minutes were 30 ± 6 µU/ml in the IGDM and 15 ± 3 µU/ml in the normals.

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

1972 ◽  
Vol 70 (2) ◽  
pp. 373-384 ◽  
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.

Insulin and glucagon in rats with Islet cell tumors Induced by small doses of streptozofoclii

1981 ◽  
Vol 59 (8) ◽  
pp. 818-823 ◽  
Author(s):  
Gen Yoshino ◽  
Tsutomu Kazumi ◽  
Soichiro Morita ◽  
Shighaki Baba
Keyword(s):  
Plasma Glucose ◽  
Islet Cell ◽  
Insulin Response ◽  
Oral Glucose ◽  
Islet Cell Tumors ◽  
Glucose Levels ◽  
Tumor Bearing ◽  
Small Doses ◽  
Wet Weight ◽  
Glucose Plasma

Plasma insulin and glucagon responses to oral glucose loading were examined in rats with islet cell tumors induced by a single intravenous injection of streptozotocin (30 or 40 mg/kg body weight). Twenty-four macroscopic and six microscopic tumors occurred in 21 rats. In 15 of 21 tumor-bearing rats, there was exaggerated insulin release in response to oral glucose. Plasma glucose levels did not rise with the oral glucose load and were comparable to those seen in normal animals. Hence these rats are described as having "responsive tumors." In six rats with "nonresponsive tumors" there was no insulin response and the plasma glucose levels rose. No significant differences in plasma glucagon levels were observed between the two groups. Nonresponsive tumors as well as responsive tumors contained a significant amount of extractable insulin (17.68 ± 8.60 and 35.07 ± 10.05 mg/g wet weight, respectively) and detectable amounts of immunoreactive glucagon (1.47 ± 0.61 and 2.24 ± 0.67 μg/g wet weight, respectively).These results suggest that a small dose of streptozotocin produces two types of islet cell tumors. One is insulin producing and insulin secreting whereas the other is insulin producing but not insulin secreting.

scholarly journals The plasma insulin and growth hormone response to oral glucose: Diurnal and seasonal observations in the antarctic

Diabetologia ◽  
1975 ◽  
Vol 11 (2) ◽  
pp. 147-150 ◽  
Author(s):  
I. T. Campbell ◽  
R. J. Jarrett ◽  
P. Rutland ◽  
L. Stimmler
Keyword(s):  
Growth Hormone ◽  
Plasma Insulin ◽  
Growth Hormone Response ◽  
Oral Glucose ◽  
Hormone Response ◽  
The Antarctic

scholarly journals Changes in Plasma Insulin-like Growth Factor (IGF)-1, IGF Binding Protein (IGFBP)-2 and IGFBP-3 during Fasting in Holstein Adult Steers and Calves

2000 ◽  
Vol 71 (2) ◽  
pp. 178-188
Author(s):  
Hong-Gu LEE ◽  
Renato Santa Ana VEGA ◽  
Long Thang PHUNG ◽  
Nobuyoshi MATSUNAGA ◽  
Hideto KUWAYAMA ◽  
...  
Keyword(s):  
Growth Factor ◽  
Plasma Insulin ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

The insulin-like growth factors and their binding proteins in a case of non-islet-cell tumour-associated hypoglycaemia

1991 ◽  
Vol 131 (2) ◽  
pp. 303-311 ◽  
Author(s):  
A. M. Cotterill ◽  
J. M. P. Holly ◽  
S. C. Davies ◽  
V. J. Coulson ◽  
P. A. Price ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Islet Cell ◽  
Plasma Insulin ◽  
Binding Proteins ◽  
Late Pregnancy ◽  
Normal Serum ◽  
Systemic Effects ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Igfbp 3

ABSTRACT Non-islet-cell tumours which induce hypoglycaemia are rare. Insulin-like growth factor-II (IGF-II) produced by some tumours is thought to be responsible for the hypoglycaemia and other systemic effects, despite normal or even low serum IGF-II levels. We studied a 44-year-old woman presenting with symptomatic hypoglycaemia associated with a large intraabdominal haemangiopericytoma. The serum IGF-II level was 455 μg/l when measured after acid-ethanol extraction (normal range (NR) 450–750 μg/l) and 1063 μg/l after acid chromatography (normal human serum pool 1068 μg/l). Levels of fasting plasma insulin, C-peptide, glucose and serum IGF-I levels were low before the operation (< 2 mU/l (NR <2-14), 0·23 nmol/l (NR 0-4-1-2), 3-1 mmol/l, (NR 3-7-5-9) and 002 U/ml respectively). After tumour removal, the symptoms resolved rapidly and the patient made a full recovery. Secretion of both insulin and growth hormone was suppressed before the operation in response to a 75 g glucose meal and to an infusion of 100 μg GH-releasing hormone (GHRH) respectively in comparison with studies after the operation. Serum IGF-II levels 6 weeks and 12 weeks after the operation fell to 385 μg/1 (777 μg/1; acid chromatography) and 280 μg/1 (647 μg/1; acid chromatography) and serum IGF-I levels increased to 0-35 U/ml and 0-26 U/ml. Serum before the operation and tumour extract contained chiefly a large molecular weight precursor IGF-II (molecular weight 15 000–20 000) which disappeared from the serum after the operation. The IGF-binding proteins (IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-4) were examined. The preoperation fasting serum IGFBP-1 level was lower than expected (31 μg/l (NR 20–70 μg/l)) and similar to levels at 6 weeks after the operation (33 μg/l). This was surprising given the differences in plasma insulin levels before and after the operation (< 2 mU/l versus 13 mU/l). Using Western ligand blotting techniques, serum IGFBP-3 levels were found to be low and IGFBP-2 appeared to be the dominant IGFBP before the operation. Serum IGFBP-3 levels after the operation fell further. This further decrease appeared, in part, to be due to the presence of a cation-dependent IGFBP-3-specific protease which has previously only been described in late pregnancy. We conclude that in this subject, despite normal serum IGF-II levels, the hypoglycaemia and systemic effects on insulin and GH secretion were due to increased bioavailability of a circulating tumour-produced precursor form of IGF-II. This increased bioavailability appears to be due to alterations in the circulating levels and perhaps affinities of the IGFBPs. Journal of Endocrinology (1991) 131, 303–311

scholarly journals Transcriptional and Posttranscriptional Regulation of Insulin-Like Growth Factor Binding Protein-3 by Cyclic Adenosine 3′,5′-Monophosphate: Messenger RNA Stabilization Is Accompanied by Decreased Binding of a 42-kDa Protein to a Uridine-Rich Domain in the 3′-Untranslated Region

1999 ◽  
Vol 13 (3) ◽  
pp. 495-504
Author(s):  
N. E. Erondu ◽  
J. Nwankwo ◽  
Y. Zhong ◽  
M. Boes ◽  
B. Dake ◽  
...  
Keyword(s):  
Growth Factor ◽  
Untranslated Region ◽  
Specific Binding ◽  
Binding Protein ◽  
Binding Activity ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Mdbk Cells ◽  
Camp Induction ◽  
Igfbp 3

Abstract The Madin Darby bovine kidney (MDBK) cell line was used to investigate the mechanisms underlying the cAMP regulation of insulin-like growth factor binding protein-3 (IGFBP-3) gene expression. Treatment of confluent monolayers either with forskolin or cAMP produced a 60- to 75-fold induction of IGFBP-3 mRNA and protein levels. This effect did not require new protein synthesis as inhibition of translation by cycloheximide actually caused a 2-fold increase in the cAMP induction. The rates of IGFBP-3 gene transcription, assessed by nuclear run-on assays, increased approximately 15-fold in cells exposed to cAMP. In addition, the half-life of the IGFBP-3 mRNA transcript was increased ∼3-fold in the presence of cAMP. Gel mobility shift and competition experiments revealed the specific binding of an approximately 42-kDa cytoplasmic protein factor to the 3′-untranslated region (3′-UTR) of the IGFBP-3 mRNA. A 21-nucleotide uridine-rich segment that contained no AUUUA motif was sufficient for the specific binding. The binding activity of this protein was reduced after cAMP treatment but was increased by phosphatase treatment. In conclusion, the cAMP induction of IGFBP-3 mRNA in MDBK cells occurred at both the transcriptional and posttranscriptional levels. The IGFBP-3 mRNA stabilization in MDBK cells probably involved the phosphorylation of a member of the family of U-rich region mRNA-binding proteins and is the first reported member whose RNA-binding activity is reduced by cAMP.

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