Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present study was to investigate the influence of nutrients and insulin on IGFs and their binding proteins (IGFBPs) during the fetal and neonatal periods of three rat populations: (a) rats undernourished by a 35% reduction in the diet from day 16 of gestation, (b) streptozotocin-induced diabetic rats from the same day, or 4 days after birth, and (c) control rats. Fetuses from the diabetic population showed a decrease in insulinemia at 19 and 21 days, along with an increase in glycemia at all stages. Neither glycemia nor insulinemia changed in the fetuses of undernourished mothers, but body weight was decreased at birth. Serum IGF-II decreased at 18 and 19 days of gestation in fetuses from undernourished mother, and increased at 18, 19 and 21 days in fetuses from diabetic mothers. Serum IGFBPs of low molecular weight (IGFBP-1 and IGFBP-2) increased in the three fetal populations studied, although no changes in serum IGFBPs were found from the effect of undernutrition or diabetes, but fetal liver IGFBP-1 mRNA expression was found to decreased in undernourished and diabetic animals as compared with controls. In neonatal rats, body weight, insulinemia and serum GH decreased in both undernourished and diabetic rats vs controls, while glycemia decreased in the undernourished and increased in the diabetic group. Serum IGF-II decreased only in diabetic rats and serum IGF-I decreased in both groups. The neonatal serum 30 kDa complex (IGFBP-1 and -2) also increased in undernutrition and diabetes parallel to the expression of mRNA. But, taken together, the changes in IGFBP peptide levels and liver mRNA expression strongly suggest that the 30 kDa complex seems to be composed mostly of IGFBP-1 in the diabetic group and of both IGFBP-1 and -2 in the undernourished animals. The studies of liver mRNA expression of IGFs and IGFBPs confirm the different metabolic control mechanism for the availability of IGFs by the IGFBPs, depending on the animal's maturity. The different adaptation shown by the diabetic neonatal population was confirmed by correlation studies between body weight, glycemia, insulinemia, IGF-I and IGFBPs. The different mechanism of adaptation in diabetic vs undernourished rats seems to be probably due to the decisive role played by hyperglycemia in the diabetic population, and also shows the crucial influence of nutritional status on IGFs and IGFBPs.
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PMID:Effects of undernutrition and diabetes on serum and liver mRNA expression of IGFs and their binding proteins during rat development. 754 53

To investigate whether previously reported increased levels of insulin-like growth factor-binding protein-1 (IGFBP-1) in GH-deficient patients only reflect decreased levels of insulin or are elevated in relation to insulin, diurnal profiles of IGFBP-1 and insulin were determined in plasma from patients with GH levels below 0.2 microgram/L throughout 24 h (n = 23) and compared to profiles from patients with insulin-dependent diabetes mellitus (IDDM; n = 9) and healthy subjects (n = 12). Samples were drawn using a continuous withdrawal technique at 20-min intervals. Levels of IGF-I were determined in one morning sample. As in healthy subjects, serum IGFBP-1 displayed a diurnal variation in GH-deficient as well as in IDDM patients, with lowest levels in the afternoon and evening and a rise with maximum levels during the night and morning. Fasting and 24-h mean levels of IGFBP-1 were significantly higher in GH-deficient patients [61 +/- 12 (P < 0.01) and 39 +/- 6 micrograms/L (P < 0.01), respectively] and IDDM patients [72 +/- 18 (P < 0.01) and 45 +/- 9 micrograms/L (P < 0.01), respectively] compared to those in healthy subjects (27 +/- 4 and 18 +/- 2 micrograms/L, respectively). Fasting levels of IGFBP-1 correlated to 24-h mean values of IGFBP-1 in all groups separately and in the combined group (r = 0.931; P < 0.001). An inverse relationship was found between IGFBP-1 and insulin in GH-deficient patients, both between 24-h mean values (r = -0.756; P < 0.001) and between fasting values (r = -0.721; P < 0.001). Corresponding values for healthy subjects were r = -0.548; P = 0.065 and r = -0.712; P < 0.01, respectively, whereas in IDDM patients the relationship was nonsignificant. Moreover, in GH-deficient patients, the diurnal mean levels of IGFBP-1 were inversely correlated to IGF-I (r = -0.477; P < 0.05) and body mass index (r = -0.450; P < 0.05). When insulin was taken into account, a tendency for a negative correlation between IGFBP-1 and IGF-I (P = 0.054) remained, whereas the relationship to body mass index disappeared. However, IGFBP-1 levels were elevated in relation to insulin levels in GH-deficient patients compared to healthy subjects (F = 48.7; P < 0.001 and F = 32.5; P < 0.001, diurnal mean values and fasting values, respectively). The majority of the IDDM patients had values in the same range as the GH-deficient patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Altered relation between circulating levels of insulin-like growth factor-binding protein-1 and insulin in growth hormone-deficient patients and insulin-dependent diabetic patients compared to that in healthy subjects. 754 95

To investigate the regulation of the IGF-I and the insulin receptor in bovine skeletal muscle, we determined their concentrations and their affinity constants in animals of different age, muscle type and breed. Receptors were solubilized and measured by an enzyme-immunoassay. During ontogenesis the concentration of IGF-I receptors decreased from 1650 /+- 600 fmol/mg protein in 3-5-month old fetuses to 105 /+- 20 fmol/mg protein in 16-month old heifers (p < or = 0.01). The insulin receptor concentrations also decreased with age from 136 /+- 28 fmol/mg protein in 3-5-month old fetuses to 50 /+- 11 fmol/mg protein (p < or = 0.05) in 16-month old heifers. In order to compare different muscle types, seven muscles, which represent large differences in fibre type composition and growth impetus, were selected from 6 month old female Jersey calves and were assayed for IGF-I and insulin receptors. We observed significant differences of the IGF-I as well as the insulin receptor concentrations between distinct muscles. However, no relationship could be established between receptor concentration and fibre type composition or growth impetus. In muscle of two cattle breeds, differing markedly with regard to muscle growth intensity, the Jersey and the German Fleckvieh breed, we observed no divergence in IGF-I nor insulin receptor concentrations. We found no differences in IGF-I and in insulin receptor affinities in any of the adult animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Exp Clin Endocrinol Diabetes 1995
PMID:IGF-I and insulin receptors in bovine skeletal muscle: comparisons of different developmental ages, two different genotypes and various individual muscles. 755 82

No differences were detected in serum IGF-I levels between lean and obese male SHFF/Mcc-fa(cp) rats expressing non-insulin-dependent diabetes mellitus (NIDDM). In contrast, serum insulin levels, and blood glucose levels were significantly elevated in obese as compared to lean littermates (P < 0.05), indicating that the obese animals were diabetic. Northern blot analysis of total tissue RNA using labeled cDNAs for IGF-I and IGF-II revealed a decrease in liver and adipose IGF-I mRNA expression in the obese littermates while IGF-II mRNA expression was decreased only in adipose tissue of obese animals as compared to lean littermates.
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PMID:Insulin-like growth factor mRNA expression in tissues of lean and obese male SHFF/Mcc-fa(cp) rats. 755 50

A 47-year-old woman was evaluated for congenital dwarfism, primary amenorrhoea due to hypogonadotrophic hypogonadism, severe hyperlipidaemia with pancreatitis, and overt diabetes mellitus associated with severe insulin resistance requiring 2.5-3 units of insulin per kilogram body weight. Chromosomal analysis with trypsin banding was normal and biochemical evaluation revealed low oestrogen levels, inappropriately low gonadotrophins, very low IGF-I concentrations and GH concentrations unresponsive to insulin or L-dopa administration. Prolactin, pituitary-adrenal and pituitary-thyroid axes were normal. Dynamic testing with GnRH and GHRH produced increases in FSH, LH and GH concentrations. A MRI of the brain revealed no discernible hypothalamic abnormalities and a small pituitary. The presence of congenital combined growth hormone and gonadotrophin deficiency on the basis of a suprapituitary defect suggests the existence of common or related pathways regulating GnRH and GHRH synthesis or secretion and may have contributed to the ultimate development of insulin resistance and hyperlipidaemia.
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PMID:Isolated combined growth hormone and gonadotrophin deficiency due to hypothalamic dysfunction, associated with insulin resistance. 755 20

The experiments reported herein were conducted to determine how corticosterone regulates growth and plasma insulin-like growth factor (IGF) I and IGF-binding protein (IGFBP) concentrations in normal and streptozotocin (STZ)-induced diabetic rats. Males were bilaterally adrenalectomized (Ax) or sham Ax and given intravenous injections of 0, 30, or 65 mg STZ per kg body wt (0, 30, or 65 STZ) to induce varying degrees of insulin deficiency and implanted with 100-mg pellets containing 0, 40, or 80% corticosterone in cholesterol. Changes in plasma IGFBP concentrations were determined by Western ligand blotting or immunoblots. Neither IGFBP-5 nor IG-FBP-6 was detected in any of the treatment groups. Plasma IGFBP-2 was elevated and IGF-I was reduced in the nondiabetic Ax rats compared with sham Ax controls, but plasma IGFBP-3 and -4 were not significantly changed. Adrenalectomy had no affect on tibial growth or plasma IGFBP-1 in these animals. Plasma IGF-I, IGFBP-1 and -3, and tibial growth were equal among 0, 30, and 65 STZ Ax rats that did not receive corticosterone. Plasma IGFBP-4 was inversely related to the amount of STZ injected in these animals, and IGFBP-2 was elevated in those given the high dose of STZ. In the 0 STZ Ax rats, plasma IGF-I and IGFBP-3 increased in proportion to the corticosterone implant dose, but IGFBP-1 was unaffected. By contrast, IGF-I and IGFBP-3 were unaltered by corticosterone in the 30 STZ Ax rats, and IGFBP-1 increased in proportion with the dose of corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1995 Dec
PMID:Corticosterone regulation of insulin-like growth factor I, IGF-binding proteins, and growth in streptozotocin-induced diabetic rats. 758 49

A specific radioimmunoassay for human IGFBP-2 was developed using a polyclonal antiserum directed against a partial sequence (hIGFBP-2(176-190)). The tracer was prepared by radioiodination of a [Tyr]o-hIGFBP-2(176-190) derivative. The assay was used to study IGFBP-2 levels in numerous clinical and experimental situations. There was little circadian fluctuations of serum level which showed a marked age-dependence with high levels at birth and senescence and low levels during puberty. Decreased IGFBP-2 levels were present in untreated insulin-dependent diabetes mellitus (IDDM), in acromegaly and during dexamethasone suppression test. GH deficiency, fasting, IGF-I administration to patients with GH receptor deficiency, hepatic failure and insulinomas caused a moderate increase of serum IGFBP-2. Markedly elevated levels were found in chronic renal failure, non-islet cell tumour induced hypoglycemia and leukaemias. The fact that all possible relationships between insulin secretion and IGFBP-2 levels could be identified suggests that insulin is not a major regulator. In general, there was an inverse relationship with serum IGFBP-3 (except IDDM) and IGFBP-2 levels were high in situations where free IGF-II should be expected to be high. The tentative conclusion would therefore be that free IGF-II is a major regulator of circulating IGFBP-2.
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PMID:Clinical studies of IGFBP-2 by radioimmunoassay. 768 12

Circulating levels and hepatic expression of insulin-like growth factor-binding protein-1 (IGFBP-1) are increased in insulin-deficient streptozotocin (STZ)-diabetic rats. Glucocorticoids stimulate and insulin suppresses hepatocellular expression of IGFBP-1 in vitro. We asked whether increased IGFBP-1 expression in STZ-diabetic animals is due to an effect of insulin deficiency per se or whether insulin deficiency represents a permissive state where glucocorticoids may play an important role in the regulation of IGFBP-1 and other circulating peptides involved in the modulation of IGF bioactivity. Intact female Sprague-Dawley-derived rats and rats undergoing bilateral adrenalectomy (ADNX) were injected with STZ (140 mg/kg) or buffer. Corticosterone acetate (50 mg/kg) or vehicle was administered to diabetic and nondiabetic animals immediately after ADNX and 24 h later. All rats were killed 48 h after surgery and/or STZ administration. Serum [125I]IGF-I-binding activity was increased 4-fold (P < 0.01), and Western ligand and immunoblotting demonstrated that levels of IGFBP-1 were high in intact STZ-diabetic animals. ADNX prevented these effects of STZ-diabetes, and corticosterone treatment restored serum IGF-binding activity and IGFBP-1 to intact diabetic levels. Similarly, Northern analysis demonstrated that the abundance of hepatic IGFBP-1 mRNA was increased 6-fold in intact STZ-diabetic animals (P < 0.01), but not in adrenalectomized diabetic animals. Corticosterone treatment restored hepatic IGFBP-1 mRNA to intact diabetic levels, and serum concentrations of corticosterone correlated with the abundance of IGFBP-1 mRNA (r = 0.475; P < 0.01), indicating that glucocorticoids play an important role in the regulation of expression of IGFBP-1 in insulin-deficient animals. In contrast, neither ADNX nor corticosterone altered the abundance of hepatic IGFBP-1 mRNA levels in nondiabetic animals. This pattern of regulation appeared to be specific; serum levels of immunoreactive IGFBP-2 and -4 tended to rise in adrenalectomized animals, and levels of IGFBP-3 were not affected by either ADNX or corticosterone treatment. Of note, serum levels of IGF-I by RIA were reduced in STZ-diabetic animals compared to control values (168 +/- 16 vs. 587 +/- 55 ng/ml, respectively; P < 0.01), were partially restored toward control values with ADNX (320 +/- 22 ng/ml), and were reduced again by corticosterone treatment (195 +/- 26 ng/ml), indicating that glucocorticoids also contribute to the regulation of IGF-I levels in insulin-deficient animals. The abundance of IGF-I mRNA was reduced in STZ-diabetic animals, and ADNX also partially prevented this effect of diabetes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of glucocorticoids on circulating levels and hepatic expression of insulin-like growth factor (IGF)-binding proteins and IGF-I in the adrenalectomized streptozotocin-diabetic rat. 769 41

To test the hypothesis that glucocorticoids inhibit muscle glucose transport apart from changes in early insulin-signaling events, we determined the effect of glucocorticoid treatment on the activation of glucose transport by both insulin and non-insulin-related stimuli (insulin-like growth factor [IGF] I and hypoxia) in rat skeletal muscle. Male Sprague-Dawley rats were treated with dexamethasone (Dex) (0.8 mg/kg for 2 days) and compared with pair-fed controls. 2-[3H]deoxyglucose (2-[3H]DG) uptake in isolated soleus muscles was measured under conditions in which uptake reflects glucose transport activity. In control muscles, 2-[3H]DG uptake was stimulated 10-fold by insulin (10 nmol/l) or IGF-I (50 nmol/l) and sixfold by hypoxia. Dex treatment decreased 2-[3H]DG uptake at all concentrations of insulin tested, reducing maximal insulin-stimulated 2-[3H]DG uptake by 41 +/- 11% (mean +/- SE, P < 0.05) and basal 2-[3H]DG uptake by 38 +/- 6% (P < 0.01). Dex treatment also inhibited 2-[3H]DG uptake at all concentrations of IGF-I tested, reducing maximal IGF-I-stimulated 2-[3H]DG uptake by 29 +/- 2% (P < 0.01), and decreased hypoxia-stimulated 2-[3H]DG uptake by 61% (P < 0.01). Dex treatment increased soleus GLUT4 protein content by 11%. Thus, Dex treatment reduces basal glucose transport and decreases the maximal response of skeletal muscle glucose transport to insulin, the related hormone IGF-I, and the non-insulin-related stimulus hypoxia. These findings support the hypothesis that, in addition to altering early insulin-signaling events, glucocorticoids may also act by inhibiting the glucose transport system, per se, perhaps by affecting GLUT4 subcellular trafficking.
Diabetes 1995 Apr
PMID:Glucocorticoid-induced insulin resistance: dexamethasone inhibits the activation of glucose transport in rat skeletal muscle by both insulin- and non-insulin-related stimuli. 769 14

Neuropathy can be a highly debilitating complication for about 10-15% of diabetic individuals. Unfortunately, the complex syndrome has proven difficult to explain and a consensus as to its cause has not emerged. It has recently come to light that insulin and insulin-like growth factors (IGFs) have neurotrophic actions on sensory, sympathetic and motor neurons. These are the main types of neurons afflicted in this disorder. Moreover, IGF activity is reduced in both clinical and experimental diabetes. The premise that insulin, IGF-I and IGF-II provide redundant neurotrophic support underlies the following new theory for pathogenesis of diabetic neural disturbances: a loss of insulin activity leads to a secondary partial decline in IGF-I activity. Although most of the redundant neurotrophic support is thereby eliminated, IGF-II activity continues to support the nervous system. The final enemy is time and the relentless age- and duration-dependent run-down of IGF activity is suggested to contribute to the age- and duration-dependent neuropathy. Weight loss or anorexia nervosa are independent risk factors that can cause a rapid, painful neuropathy to develop as a result of a rapid loss of IGF activity. A distinguishing feature of this new theory is that hyperglycemia is not considered to be the main culprit. The following critical predictions from the theory were tested in diabetic rats: (i) IGF activity is reduced in diabetic neural tissues; (ii) conduction velocity is impaired in the diabetic spinal cord; (iii) replacement therapy with IGF can prevent neuropathy in diabetic nerves; and (iv) IGFs can prevent diabetic neuropathy, despite hyperglycemia. All of these predictions have been validated. It is hoped that a fresh perspective will stimulate renewed study into the causation of this most unfortunate disorder.
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PMID:Implication of insulin-like growth factors in the pathogenesis of diabetic neuropathy. 771 67


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