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

Serum insulin-like growth factor (IGF) and IGF-binding protein (IGF BP) levels were determined in 13 insulin-dependent diabetic patients (30-60 yr of age) during an episode of severe metabolic decompensation and the recovery phase. After separation by acidic gel filtration, the samples were assayed for IGF using a protein-binding assay (which measures mainly IGF I-related peptides) and for IGF BP by measuring the binding activity, in both assays using IGF I as tracer. The reference standard was a pool of normal adult serum with an assigned potency of 1 U IGF and 1 U IGF BP per ml. The mean IGF level in the uncontrolled state, 0.55 +/- 0.05 (SEM) U/ml, was about half that of normal subjects (1.03 +/- 0.03 U/ml, P less than 0.001). With treatment, IGF levels reached the normal range within 3 days. The pattern of changes in IGF BP levels was roughly similar, although the values in the uncontrolled state were less depressed (0.78 +/- 0.04 U/ml vs. 0.98 +/- 0.04 in normal subjects, P less than 0.01). Highly significant correlations (P less than 0.001) were found between IGF levels and the biological parameters reflecting control of the diabetes: glycosuria (r = -0.60), glycemia (r = -0.52), ketonemia (r = -0.65), and HCO3- (r = 0.58). Similar but less significant correlations were found for IGF BP. The mean GH level during the period of metabolic decompensation (9.0 +/- 1.5 ng/ml) was elevated compared to that after recovery (2.9 +/- 0.8 ng/ml) (P less than 0.025). There was a negative correlation between GH values and IGF levels (r = -0.67, P less than 0.001). The correlation with IGF BP was much less significant (r = -0.38, P less than 0.05). The results clearly reflect the role of insulin and nutritional factors in the control of IGF levels. They also support the notion that the biosynthesis of IGF and IGF BP is not regulated in the same way.
 ...
PMID:Serum levels of insulin-like growth factor (IGF) and IGF binding protein in insulin-dependent diabetics during an episode of severe metabolic decompensation and the recovery phase. 257 89

The question still remains: What is best for the patient? It appears that whole organ or segmental pancreas transplantation can be carried out, giving anywhere from a 46% to an 84% 1-year pancreas survival rate. At the moment there is no clear-cut evidence that patient survival--at least in the short term--is any better after a combined pancreas-kidney graft than after a kidney graft alone, and there are more complications from the combined procedure. It appears once again that patient survival is a function of control of ketoacidosis and its complications--whether by a pancreas graft or by better insulin delivery. Nevertheless, several things have been learned: (1) Patients who receive a pancreas-kidney graft simultaneously have the best pancreas 1-year survival. (2) A pancreatic graft without a simultaneous kidney graft does poorly. (3) A pancreas graft carried out after a kidney graft will not do as well. (4) A kidney transplanted to a diabetic patient may become nephropathic unless supported by a pancreatic graft. (5) Retinopathy is not improved by pancreatic transplantation. (6) Neuropathy is improved or stabilized by pancreatic transplantation. (7) Nephropathy is improved by pancreatic grafting. (8) There is no clear-cut difference in pancreatic graft survival, whether segmental or whole organ grafts are used. (9) Bladder-drained grafts appear to have slightly better survival at 1 year than enteric-drained or polymer-injected grafts. (10) Human islet cell homotransplantation is not yet an accomplished fact. As Barker has pointed out, the potential benefits of pancreatic grafting are for those who are prone to complications and who do not have irreversible diabetic complications. Predicting those in whom significant complications will develop is not easy, and a large percentage of the grafts done to date have been done for patients with end stage renal disease. It has been suggested that transplants are best used for those with early renal disease and for those with pre-proliferative retinopathy and for those that are metabolically difficult to handle with insulin and for those at high risk for complications with diabetes: namely, those with high levels of inactive renin that are associated with microvascular complications and high levels of insulin-like growth factor. These complications seem to be associated with accelerated progression of retinopathy. Diabetic children whose disease is associated with major neurovascular disease and children with impaired counter regulatory mechanisms may also be candidates for grafting.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Where are we with pancreas transplantation? 268 60

Diabetes is associated with a fall in serum levels of insulin-like growth factor-1/somatomedin-C (IGF-1/Sm-C) and a rise in somatomedin inhibitor, a factor which antagonizes somatomedin action. We attempted to determine if the presence of glucocorticoids was required for diabetes-related alterations in these circulating growth factors. Diabetes was induced with streptozotocin in intact or adrenalectomized rats. Adrenalectomized-nondiabetic and adrenalectomized-diabetic rats were given either no glucocorticoids or daily hydrocortisone acetate at 0.5 or 50 mg/kg body weight, and killed 48 hours after streptozotocin treatment. After serum fractionation via size exclusion high performance liquid chromatography (HPLC), IGF-1/Sm-C was determined by radioimmunoassay, and somatomedin inhibitor by bioassay according to the ability of serum fractions to blunt cartilage stimulation by normal serum. Intact-diabetic rats had 22% weight loss, glucose 427 mg/dL, and beta-hydroxybutyrate 7.2 mmol/L (all P less than .001 v control). Serum IGF-1/Sm-C levels in intact-diabetic rats were decreased 71%, while somatomedin inhibitor rose to 470% of the control values (both P less than .004). Adrenalectomized-diabetic rats displayed comparable hyperglycemia (greater than 400 mg/dL) and decline in IGF-1/SmC, with or without glucocorticoid replacement. However, adrenalectomized-diabetic rats had greatly reduced weight loss (10%), beta-hydroxybutyrate (1.5 mmol/L), and somatomedin inhibitor (59% of control), all P less than .01 v intact-diabetic. Hydrocortisone 0.5 mg/kg in these animals increased weight loss but had no significant effect on beta-hydroxybutyrate or somatomedin inhibitor levels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Glucocorticoid effects on IGF-1/somatomedin-C and somatomedin inhibitor in streptozotocin-diabetic rats. 272 99

Tumor-promoting phorbol esters alter binding of growth factors and hormones to their specific receptors. Action of diacylglycerols, endogenous phorbol ester analogues, on 125I-labeled insulin binding to its receptor from human cells was therefore investigated. A variety of 1,2-diacylglycerols and 1,3-diacylglycerols inhibited 125I-insulin binding to intact human monocyte-like (U-937) and lymphoblastoid (IM-9) cells in a dose-, time-, and temperature-dependent manner within 30 sec at 37 degrees C in a fashion analogous to that of the tumor-promoting phorbol diester 12-O-tetradecanoylphorbol-13-acetate (TPA). Inhibition of insulin binding by diacylglycerols, analyzed by Scatchard plot, seems to be due to altered binding affinity of the insulin receptor. Diacylglycerol effects were reversible, were seen regardless of the order of addition of 125I-insulin and diacylglycerols, and were demonstrated only with occupied insulin receptors. Corresponding fatty acids or phospholipids did not affect specific insulin binding to the intact U-937 cells. Diacylglycerols also inhibited binding of 125I-insulin-like growth factor (IGF) I but not that of 125I-human growth hormone (HGH) to the human cells. The non-tumor-promoting phorbols (phorbol, 4-alpha-phorbol, phorbol-12,13-distearate) did not affect insulin binding to intact cells. Both diacylglycerols and TPA stimulated internalization of 125I-insulin by U-937 and IM-9 cells. The ability of diacylglycerol to mimic the effects of TPA on the insulin receptor supports the concept of diacylglycerols as endogenous phorbol diester analogues even though the sole role of protein kinase C in our system is doubtful.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Dec
PMID:Diacylglycerol modulation of insulin receptor from cultured human mononuclear cells. Effects on binding and internalization. 353 83

Despite reports of reduced serum insulin-like growth factor (IGF) levels in experimentally diabetic animals, human diabetic patients have been reported to have decreased, normal, or even elevated levels. This study was a cross-sectional examination of the effect of age on immunoreactive IGF-I levels in adult patients with insulin-dependent or noninsulin-dependent diabetes mellitus (IDDM and NIDDM) attending a diabetes out-patient clinic. The patients and normal subjects studied were divided into the age ranges 21-30, 31-40, 41-50, 51-60, and over 60 yr. For all ages combined, the mean IGF-I level (+/- SD) was 0.84 +/- 0.26 U/ml (202 +/- 62 ng/ml) in 133 normal subjects, significantly reduced to 0.41 +/- 0.17 U/ml in 121 IDDM patients, and 0.49 +/- 0.19 U/ml in 46 NIDDM patients (both P less than 0.001). In both groups there was a marked decline in IGF-I with increasing age (P less than 0.01). Except for NIDDM patients aged 21-30 yr (only two patients), IGF-I levels in both IDDM and NIDDM patients were significantly lower in every age range than those in age-matched normal subjects, but did not differ between the two diabetic groups. Glycosylated hemoglobin levels correlated inversely with IGF-I levels only in younger patients with IDDM (r = -0.486; P less than 0.05 for patients aged 21-40 yr). We conclude that factors common to IDDM and NIDDM, perhaps related to relative nutritional deficiency at the cellular level, cause a reduction in serum IGF-I levels, and that this reduction occurs independently of age-related changes in IGF-I.
 ...
PMID:Serum insulin-like growth factor I levels in adult diabetic patients: the effect of age. 373 35

The concentrations of somatomedins/insulin-like growth factors were measured by a specific radioimmunoassay for insulin-like growth factor-I and a specific radioreceptor assay for insulin-like growth factor-II in sera of term normal and Type 1 (insulin-dependent) diabetic pregnant women and in various cord sera of their newborn infants. Serum insulin-like growth factor-I levels in normal (non-diabetic) maternal serum were higher than in non-pregnant women (486 +/- 26 versus 215 +/- 26 ng/ml). The normal pregnancy-induced increment of insulin-like growth factor-I was markedly reduced in diabetic pregnancy. It was not different in patients with good or poor glycaemic control, as judged by normal or elevated blood levels of haemoglobin A1c content. Insulin-like growth factor-I levels in cord serum of infants of diabetic women with good glycaemic control (86 +/- 11 ng/ml) and poor glycaemic control (91 +/- 19 ng/ml) were significantly higher (p less than 0.01) than in infants of non-diabetic women (43 +/- 42 ng/ml). The fetal birth weight ratios were not significantly correlated with insulin-like growth factor-I levels in cord serum. Serum insulin-like growth factor-II levels in maternal and cord serum in diabetic and normal pregnancy were not different from each other or from normal non-pregnant women. The increment in insulin-like growth factor-I levels in maternal serum in pregnancy may influence placental structure and function. Lack of this increment in maternal diabetes may have direct implication in placental abnormalities in diabetes and indirect implications on fetal development and metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Insulin-like growth factors (IGF) I and II in diabetic pregnancy: suppression of normal pregnancy-induced rise of IGF-I. 381 36

Molecular hybridization, monoclonal antibody, and electron microscopic analyses showed lymphocytic choriomeningitis virus (strains Armstrong and WE) persistently infecting cells of the islets of Langerhans in BALB/WEHI mice. When monoclonal or monospecific antibody conjugated with two different fluorochrome dyes was used to mark insulin-containing beta cells or viral antigens, viral nucleoprotein was identified predominantly in beta cells. Electron microscopy confirmed these findings by showing virions budding from the beta cells. Persistent infection was associated with chemical evidence of diabetes (hyperglycemia, abnormal glucose tolerance, and normal or low-normal concentrations of insulin). Concentrations of cortisol and insulin-like growth factor in blood were normal, as was the level of growth hormone in the pituitary gland. The virus-infected islet cells showed normal anatomy and cytomorphology. Neither cell lysis nor inflammatory infiltrates were routinely seen. Thus a virus may persistently infect islet cells and provide a biochemical and morphological picture comparable to that of early adult-onset diabetes mellitus in humans.
 ...
PMID:Virus persists in beta cells of islets of Langerhans and is associated with chemical manifestations of diabetes. 620 72

The receptors for insulin and the insulin-like growth factor (IGF) I are two structurally homologous disulfide-linked multisubunit complexes of apparent Mr = 350,000. The similar subunit structures of these two types of receptors suggested that their genetic expression might be affected by common genetic defects. We have examined this possibility in an insulin-resistant, diabetic patient who exhibits decreased insulin binding activity. The receptors for IGF-I and insulin in skin fibroblasts from this patient were affinity labeled with 125I-IGF-I and 125I-insulin, respectively, and visualized by electrophoresis and autoradiography in polyacrylamide gels. Control fibroblasts exhibited the usual affinity labeling of the disulfide-linked Mr = 350,000 insulin and IGF-I receptor structures. The intensity of labeling of both receptor types in the patient's fibroblasts was less than in control fibroblasts. Binding data indicated that this decrease is due to a decreased receptor number with little or no decrease in affinity for the respective ligands. The high-affinity IGF-II receptor in fibroblasts affinity labeled with 125I-IGF-II or 125I-IGF-I consists of a single polypeptide not disulfide linked to any other membrane component. The molecular size and intensity of labeling of the IGF-II receptor in the patient's fibroblasts were unaltered when compared with those of controls. These observations suggest that a common genetic defect alters the expression of the homologous receptor structures for insulin and IGF-I.
Diabetes 1983 Jun
PMID:Parallel decreases in the expression of receptors for insulin and insulin-like growth factor I in a mutant human fibroblast line. 631 54

A possible role for growth hormone (GH) in stimulating islet B-cell replication was examined in neonatal rat pancreatic monolayer cultures. Addition of ovine GH (1000 ng/ml) to serum-free medium for 2 days resulted in a significant increase (+114%) in [3H]thymidine labeling of B-cells in aldehyde-thionine-stained autoradiographs, and a similar increase in the B-cell mitotic index. The stimulatory effects of GH on islet B-cell replication were greatest in serum-free medium, unaffected by glucose concentrations (2.8--16.7 mM), and not accompanied by any stimulation of insulin release. The threshold concentration of GH for a significant stimulatory effect on B-cell replication was 30 ng/ml. The insulin-like growth factor, multiplication stimulating activity (MSA), also effectively stimulated B-cell replication. Although some effects of GH are mediated by the insulin-like growth factors (IGFs), the effects of GH on B-cell replication did not appear to be mediated by IGFs since (1) the maximal effect of GH (+156%) was significantly greater than that of MSA (+91%); (2) the combination of maximal stimulatory concentrations of GH and MSA produced an additive effect; and (3) a significant effect of GH on B-cell replication was observed as early (8 h) as that produced by MSA. These results suggest that GH can stimulate islet B-cell replication directly, and that this effect may not depend on production of either insulin-like growth factors.
Diabetes 1983 Apr
PMID:Growth hormone stimulates islet B-cell replication in neonatal rat pancreatic monolayer cultures. 633 3

A possible role for insulin in stimulating islet beta-cell replication was examined in neonatal rat pancreatic monolayer cultures. Addition of insulin to serum-free medium increased the mitotic index and stimulated dose-dependent increases in [3H]-thymidine incorporation in nuclei of islet beta-cells in aldehyde-thionine-stained autoradiographs. The effects of insulin were not associated with any significant changes in glucagon or somatostatin levels in the culture media. Multiplication stimulating activity (MSA), an insulin-like growth factor, was about 100-fold more potent than insulin: 3 ng/ml MSA stimulated a half-maximal increase in thymidine labeling of beta-cell (+63%, P less than 0.005), whereas 300 ng/ml insulin was required for a similar effect. The maximal effects of insulin and MSA were similar, and the combination of maximal stimulatory concentrations of MSA (30 ng/ml) and insulin (3000 ng/ml) was not more effective than either substance added alone, suggesting that both peptides act on the same mechanism(s) regulating beta-cell replication. Furthermore, an antibody to the insulin receptor did not prevent the stimulatory effects of either insulin or MSA on thymidine labeling of beta-cells. These results demonstrate that insulin can stimulate islet beta-cell replication directly, possibly through a receptor for MSA or another insulin-like growth factor.
Diabetes 1982 Feb
PMID:Insulin and multiplication stimulating activity (an insulin-like growth factor) stimulate islet (beta-cell replication in neonatal rat pancreatic monolayer cultures. 675 33


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>