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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptozotocin diabetes prevents induction of pancreatic tumors in several animal models, suggesting a pivotal role for islet cell products in the pathogenesis of pancreatic cancer. To test the hypothesis that altered gastrointestinal peptide levels in streptozotocin diabetes influence tumor growth, human pancreatic cancer cells (MIA PaCa-2) were implanted subcutaneously into streptozotocin diabetic nude mice. After 3 weeks, tumors in the control group weighed 43 mg and tumors in the diabetic group weighed 12 mg (P < 0.001). Plasma insulin and IGF-1 levels were significantly decreased in the streptozotocin-treated animals compared to those of control (insulin: 23 microU/ml vs 31 microU/ml, P < 0.001; IGF-1: 254 ng/ml vs 324 ng/ml, P < 0.001). In contrast, somatostatin and glucagon were significantly elevated in the streptozotocin diabetic group relative to control levels (somatostatin: 179 pg/ml vs 54 pg/ml, P < 0.001; glucagon: 290 pg/ml vs 134 pg/ml, P < 0.001). Competitive binding studies revealed specific cell surface receptors for insulin (Kd = 15.5 nM), IGF-1 (Kd = 30.0 nM), and somatostatin (Kd = 2.5 nM) on the MIA PaCa-2 cells. Receptors for glucagon were absent. In an in vitro cell proliferation assay, cell division was promoted by insulin (P < 0.01, max + 11%) and IGF-1 (P < 0.01, max + 10%). Somatostatin inhibited cell division (P < 0.01, max - 18%). No effect was seen with glucagon. The growth of pancreatic cancer, particularly in diabetes, may be influenced by gut peptides in a receptor-dependent fashion.
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PMID:GI hormonal changes in diabetes influence pancreatic cancer growth. 779 56

The clinical features of insulin receptor disorders found in Japan are summarized. About 20 cases of primary receptor mutations (type A syndrome of insulin resistance, leprechaunism and Rabson-Mendenhall syndrome) and 16 cases of autoantibodies against insulin receptor (type B syndrome of insulin resistance) are described in Japan. There was a trial of IGF-1 for some of the patients, revealing its usefulness.
Diabetes Res Clin Pract 1994 Oct
PMID:Insulin receptor disorders in Japan. 785 97

Chronic renal failure (CRF) is characterized by a series of compensatory adaptations in the surviving nephrons of the diseased kidney aimed at maintaining glomerular filtration rate and tubular resorptive functions. Several lines of evidence indicate that in normal kidney growth hormone (GH) and insulin-like growth factors (IGFs) modulate the nephron, both in respect to function and size. Virtually all members of the GH/IGF axis are present in the kidney, comprising: 1) GH-receptors; 2) IGF-1 and IGF-2 mRNA; 3) distinct receptors for IGFs: the IGF-1 receptor and the IGF-2/mannose-6-phosphate receptor, and 4) specific binding proteins (IGFBPs), indicating that GH and IGFs may affect the kidney in both an endocrine and autocrine/paracrine fashion. GH and IGFs modulate renal metabolism and the kidney plays an important role in the metabolism and degradation of circulating GH and IGFs. The action of GH to enhance kidney function and size is mediated through IGF-1, and IGF-1 infusion in animals and man stimulates renal function and volume. In addition, renal growth following various pathophysiological conditions (e.g. reduction in renal mass, diabetes mellitus) is preceded by an increase in endogenous renal IGF-1. In CRF circulating levels of GH are elevated, serum IGF-1 is normal and circulating IGFBP-1, -2, and -3 are elevated. Given the ability of GH and IGF-1 to stimulate various functions of the kidney, the potential use of GH or IGF-1 in the setting of CRF has been suggested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The growth hormone/insulin-like growth factor axis in the kidney: aspects in relation to chronic renal failure. 806 65

The function of insulin receptor and IGF-1 receptor was investigated in placentas from 10 healthy control mothers, 8 diabetic mothers with appropriate-for-gestational-age babies (AGA group) and 9 diabetic mothers with large-for-gestational-age babies (LGA group). None of the diabetic mothers were obese before pregnancy; their blood glucose was well controlled during pregnancy and glycosylated HbA1c was 6.52 +/- 0.71% (M +/- S.E.). Insulin and IGF-1 receptors were partially purified from placentas using wheat germ agglutinin chromatography. The insulin-binding capacity was significantly increased in both the AGA and the LGA groups compared to the control, whereas the IGF-1 binding capacity was similar in the three groups. Autophosphorylation studies were performed with partially purified receptors equalized for similar binding capacity, then immunoprecipitated with anti-insulin receptor antibody or anti-IGF-1 receptor antibody. Insulin-stimulated 32P-incorporation into the insulin receptor beta-subunit was increased by 133% in the LGA group versus the control, whereas incorporation in the AGA group was equivalent to the control. Insulin-stimulated tyrosine kinase activity of the receptor preparation for histone H2B phosphorylation was also significantly increased in the LGA group compared to the control. 32P-incorporation into beta-subunit IGF-1 receptor and IGF-1-stimulated tyrosine kinase activity did not show any significant differences among the three groups. The data in the present study suggest that elevated insulin receptor kinase might be involved in fetal overgrowth in diabetic mothers.
Diabetes Res Clin Pract 1994 Jan
PMID:Insulin-receptor kinase is enhanced in placentas from non-insulin-dependent diabetic women with large-for-gestational-age babies. 820 Feb 91

Glomerular hypertrophy is reported in several endocrine disorders such as acromegaly and diabetes mellitus, where abnormalities of growth hormone and insulin-like growth factor (IGF-I) have been reported. In the present report, we have cultured bovine and human glomerular endothelial cells, and bovine glomerular epithelial and mesangial cells, and characterized the expression of IGF-I mRNA and its receptor in these cells. High affinity, specific receptors for IGF-I were identified in all three types of cells by radioreceptor assays. Receptor number (Ro) derived by Scatchard analysis revealed an unusually high number of Type I IGF receptors, approx. 1.2 x 10(5) receptors/cell in glomerular endothelial cells. Affinity crosslinking studies and immunoprecipitation with antibodies against the Type I IGF receptor identified the alpha-subunit of the IGF-I receptor as having a molecular mass of 140 kDa. Biologically, IGF-I was more potent than insulin or IGF-II in stimulating DNA synthesis in glomerular endothelial cells. Northern blot analysis showed that glomerular and aortic endothelial cells expressed IGF-1 mRNA of 1.7 kb. In contrast, renal glomeruli showed several IGF-1 mRNAs of 7.5, 1.7 and 1.2 kb. Thus, the demonstration of both a prepondence of Type I IGF receptors coupled with the growth promoting effects of IGF-I in glomerular endothelial and epithelial cells, as well as the local production of IGF-I mRNA suggests that IGF-I serves an important role as an autocrine or paracrine regulator of the growth of renal glomeruli.
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PMID:Characterization of type I IGF receptor and IGF-I mRNA expression in cultured human and bovine glomerular cells. 826 20

FSH in vitro stimulates increased oxygen uptake by isolated follicular granulosa cells from immature rats treated with diethylstilbestrol (DES) when substrates are present (glucose, glutamate, pyruvate or fumerate) or are completely absent. However, when glucose is the only substrate or when any single substrate is omitted from the buffer, FSH has no effect. FSH in vitro also increases the uptake of glucose and the formation of 14CO2 from [1-6 14C]-glucose. Granulosa cells from diabetic immature rats treated with DES did not show increased oxygen uptake with in vitro FSH. Diabetic cells had similar receptor binding of FSH to that of control non-diabetic cells. The addition of both insulin and FSH in vitro to buffer with diabetic granulosa cells gave increased oxygen uptake over that of control cells from diabetic rats. The insulin stimulation of oxygen uptake by FSH in cells from diabetic rats was not duplicated by either epidermal growth factor (EGF) or insulin-like growth factor I (IGF-1). Follicle counts of ovaries from diabetic and control immature rats treated with DES showed increased atresia in the diabetic ovaries after only 44 hr. of diabetes. Follicle counts of ovaries from adult diabetic rats showed increased atresia in 24 hours after induction of diabetes at proestrus. Follicle counts of pseudopregnant rats showed increased atresia by 3 days after diabetes was induced. We conclude that diabetes prevents normal follicle growth stimulated either by exogenous DES or by endogenous hormones secreted during proestrus.
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PMID:Diabetes prevents the normal responses of the ovary to FSH. 828 34

Endothelin, a vasoconstrictor peptide secreted from endothelial cells, has been thought to play a role in various forms of vascular disease. Diabetes mellitus is well known for its association with accelerated atherosclerosis and microvascular damage. Although the basis for the vessel insult is multifactorial, hyperinsulinemia is thought to contribute by an unknown mechanism. In this study, we sought to determine whether insulin stimulates the production and secretion of ET-1 as a possible basis for the association of hyperinsulinemia and vascular disease. We demonstrated that insulin significantly stimulates the gene expression and secretion of ET-1 from cultured BAEC, and that insulin increases ET-1 mRNA expressed in BBCEC. Insulin caused a maximal twofold inducement above control ET-1 mRNA expression in a dose-related fashion in BAEC. The increased mRNA resulted from increased transcription, as determined by nuclear run-off studies. Increased ET-1 mRNA was seen after 4 h of incubation with insulin: the peak occurred at 6-8 h and persisted for 24 h. Insulin caused as much as a fourfold stimulation of ET-1 secretion from BAEC in a dose-related fashion, including a twofold increase at a physiological concentration (10(-9) M): The increase began at 1 h of incubation and continued for the entire 24-h incubation period. The insulin-induced increases in both ET-1 mRNA and ET-1 protein secretion were significantly attenuated by genistein, a tyrosine kinase inhibitor. This stimulation probably occurred through the insulin receptor, because IGF-1 had no effect on ET-1 gene expression or secretion from these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Feb
PMID:Insulin stimulates production and secretion of endothelin from bovine endothelial cells. 842 73

Insulin receptor substrates-1 (IRS-1) is the major cytoplasmic substrate of the insulin and IGF-1 receptors. Recent studies have identified multiple sequence variants of IRS-1, especially in patients with non-insulin-dependent diabetes mellitus. In the present study, we have examined insulin-stimulated processes in 32D(IR) cells, a myeloid progenitor cell stably overexpressing the insulin receptor, transfected with wild-type human-IRS-1 or the most common human variant of IRS-1 in which glycine 972 is replaced by arginine. As compared to wild-type IRS-1, insulin stimulation of cells transfected with mutant IRS-1 exhibited a 32% decrease in incorporation of [3H]thymidine into DNA (P = 0.002), a 36% decrease in IRS-1 associated phosphatidylinositol (PI) 3-kinase activity (P = 0.004) and a 25% decrease in binding of the p85 regulatory subunit of PI 3-kinase to IRS-1 (P = 0.002). There was also a tendency for a decrease in Grb2 binding to IRS-1 and insulin-stimulated mitogen-activated protein kinase activity, however, these were not statistically significant. The changes occurred with no change in insulin receptor or IRS-1 tyrosine phosphorylation. These data indicate that the mutation in codon 972 in IRS-1 impairs insulin-stimulated signaling, especially along the PI 3-kinase pathway, and may contribute to insulin resistance in normal and diabetic populations.
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PMID:A common amino acid polymorphism in insulin receptor substrate-1 causes impaired insulin signaling. Evidence from transfection studies. 864 50

High growth hormone levels in patients with insulin-dependent diabetes were recognised 25 years ago. For many years this has been explained as an epiphenomenon of poor metabolic control. The natural course of the disease is characterised by gradual loss of residual beta-cell function and parallel elevations of plasma growth hormone and can be divided into three consecutive phases. It appears that the hormonal changes observed are determined by the IGF-1 generating capacity of the liver which, in turn, is dependent on the synergistic stimulating action of growth hormone and portal insulin. The first (initial) phase of insulin-dependent diabetes mellitus is characterised by the absence of insulin, high growth hormone levels and low plasma IGF-1. The pituitary growth hormone response to exercise and other stimuli is pathological. The second phase of disease ('C-peptide positive phase') is characterised by the return of some residual beta-cell insulin secretion, increased levels of growth hormone compared to non-diabetic subjects, physiological IGF-1 levels and near normal pituitary growth hormone responses to different agents. The third phase of the disease is characterised by complete loss of endogenous insulin secretion, very high plasma growth hormone levels, low normal plasma IGF-1 but impaired hepatic IGF-1 generating capacity. The control mechanisms of pituitary growth hormone secretion (long loop negative feedback and auto-feedback), are disturbed.
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PMID:Natural course of growth hormone hypersecretion in insulin-dependent diabetes mellitus. 869 39

The levels of endothelins 1 and 2 (ET-1 and ET-2) have been examined in 415 follicular fluids of 57 women participating in the IVF-ET programme in the University Women's Hospital, Marburg, in relation to the morphological appearance ("maturity") and fertilizability of harvested oocytes as well as to the levels of inhibin, FSH, IGF-1, estradiol and progesterone. Follicular aspiration was done transvaginally in all patients after down regulation with nafareline and ovarian stimulation using urofollitropin and menotropin. Ovulation was induced by hCG. ETs were measured by RIA using commercial kits supplied by Peninsula Laboratories, Belmont, CA. For FF samples, ET-1 and ET-2 RIAs were revalidated. Immunoreactive ET-1 was detectable in all follicular samples, the average level being 18.5 +/- 11.8 pg/ml, ET-2 was present only in 67.5% of the samples, the average level being 13.6 +/- 16.3 pg/ml. There was no significant difference in the average levels of ET-1 in the fluids of small, medium and large follicles. However, there was a significantly higher level of ET-2 in the fluids of medium compared to large follicles and there was a negative correlation of the ET-2 levels to the volume of the follicle (p < 0.01) which suggests that ET-2 could play a role during the maturation of the ovarian follicles. Unlike ET-1, the mean concentrations of ET-2 were significantly higher in the fluids with oocytes which could be fertilized and cleaved than in those with oocytes which did not fertilize or cleave, thus indicating a role for ET-2 in the process of oocyte maturation. No correlations of ET levels were found with the levels of inhibin, FSH, estradiol and progesterone. However, ET-2 levels significantly correlated with the levels of IGF-1 (p < 0.001) indicating a possible synergistic effect of endothelins and IGF-system. In conclusion, this study is further evidence for a physiological role of the ETs in the human ovary.
Exp Clin Endocrinol Diabetes 1996
PMID:Human follicular fluid levels of endothelins in relation to oocyte maturity status. 875 May 75


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