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)

Primary cultures of microvascular endothelial cells and isolated adipocytes were prepared from human omental adipose tissue to study the potentially overlapping roles of insulin and insulinlike growth factors (IGFs) in human adipose tissue. To determine whether adipocytes contain type I IGF receptors, binding experiments were carried out with 125I-labeled IGF-I. At 16 degrees C, saturation of specific binding to adipocytes was reached after 30 min and was 0.7% per 10(6) cells. At 37 degrees C, chloroquine produced an increase in cell-associated 125I-IGF-I, suggesting that IGF-I is internalized and degraded in a manner analogous to insulin. In competition experiments, IGF-I competed for binding more effectively than rat IGF-II or insulin. The concentrations of IGF-I, rat IGF-II, and insulin necessary to displace 50% of 125I-IGF-I binding were 2.5, 15, and 90 nM, respectively. In addition, a monoclonal antibody (alpha-IR3) that has been shown to block the type I IGF receptor was used in competition binding experiments. The antibody also inhibited binding of 125I-IGF-I to adipocytes. The biological effects of insulin and IGF-I were examined by studying adipocyte lipoprotein lipase (LPL). Insulin stimulated [14C]glucose incorporation into cellular lipid in a dose-dependent manner, with 50% effective concentration (EC50) of 0.3 nM. However, an increase in LPL activity was observed only at a high insulin concentration, with an EC50 of approximately 30 nM. In contrast, IGF-I stimulated a progressive increase in LPL, with an EC50 of 3.2 nM. In addition, alpha-IR3 blocked the stimulatory effect of IGF-I on adipocyte LPL.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Jun
PMID:Insulinlike growth factor action and production in adipocytes and endothelial cells from human adipose tissue. 254 8

IGF-I and IGF-II as well as the low molecular type of IGF binding protein (IGFPB) were determined in serum from 11 adolescents with insulin-dependent diabetes mellitus (IDDM) during a cross-over study with conventional and continuous subcutaneous insulin infusion (CIT and CSII) therapy. At the onset of the study the mean IGF-I level, 127 +/- 15 ng ml-1, was significantly decreased (P less than 0.001) in comparison with age-matched controls, whereas the mean IGF-II level, 1024 +/- 48 ng ml-1, was increased. A significant correlation (r = 0.70, P less than 0.05) was found between IGF-II and HbA1c levels. The mean morning level of IGFBP, 75 +/- 17 ng ml-1, at the onset of the study, was increased threefold above that in age-matched controls (P less than 0.01). There was a significant correlation between IGFBP and blood glucose values (r = 0.66, P less than 0.05). During CSII therapy a significant decrease (P less than 0.05) of the IGFBP levels was seen in subjects with a decrease in glucose levels, whereas no change was observed in IGF levels. The findings of elevated IGF-II and IGFBP levels and correlations between IGFBP and blood glucose concentration as well as IGF-II and HbA1c levels in adolescents with IDDM indicate that both IGF-II and IGFBP reflect a deranged metabolism caused by inadequate insulin administration.
 ...
PMID:Serum levels of insulin-like growth factor (IGF) I, II and IGF binding protein in diabetic adolescents treated with continuous subcutaneous insulin infusion. 254 27

The maternal and fetal endocrine pancreas were investigated in the diabetic BB rat on day 21 of pregnancy. The maternal pancreas of the diabetic rat contained practically no insulin-positive B cells. The A and D cell mass were also decreased, while plasma glucagon and somatostatin levels were normal or increased, confirming previous data. Six of 11 diabetic rats had B-cell-specific surface antibodies (ICSA), whereas only 1 of 10 nondiabetic rats was ICSA-positive. The volume density of insulin-positive cells was decreased in the fetal pancreas of diabetic BB rats compared to fetuses of nondiabetic rats, but the volume density of glucagon- and somatostatin-positive cells remained normal. The B cells of these fetuses were ultrastructurally less granulated and showed signs of increased cellular activity. Plasma insulin levels were decreased while plasma glucagon and somatostatin concentrations were normal. ICSA were not detected in fetuses of nondiabetic and diabetic rats. There were no differences in the histology of the spleen and thymus between both groups of fetuses. Metabolic characterization of the growth-retarded fetuses of diabetic rats revealed, besides lower plasma insulin concentrations, increased branched chain amino acid levels, and normal plasma Sm/IGF-I levels. The main conclusions from this study are: (1) Severe maternal diabetes decreases the pancreatic insulin-positive cell mass and plasma insulin levels in the fetus, but not the A and D cell mass and function; (2) ICSA are not detectable in fetal plasma; (3) the influence of maternal BB rat diabetes on fetal endocrine pancreas and metabolic environment resembles that of severe streptozotocin-induced diabetes.
 ...
PMID:Maternal and fetal endocrine pancreas in the spontaneously diabetic BB rat. 256 32

Insulin-deficient, streptozotocin-diabetic rats show severe metabolic disturbances and stop growing. Besides insulin, these animals also lack growth hormone and insulin-like growth factor-I. We examined whether or not growth parameters correlate with IGF-I serum levels in young rats with streptozotocin-diabetes of different severity. In the diabetic rats, blood glucose varied between 18.4 and 38.6 mmol/l (healthy controls between 6.1 and 9.3), IGF-I serum levels between 2.6 and 15.6 nmol/l (controls between 19.6 and 26.5), and serum insulin levels between 0.05 and 0.14 nmol/l (controls between 0.36 and 0.55). We found a highly significant linear correlation between IGF-I serum levels and the two investigated growth parameters, tibial epiphyseal width and longitudinal tibial bone growth. The finding that these indices of growth are strongly correlated with IGF-I serum levels in young rats with diabetes of different severity, suggests that IGF-I is a major determinant of growth. This is in keeping with our earlier demonstration that exogenously infused IGF-I promotes growth in diabetic rats.
 ...
PMID:The role of insulin-like growth factor I in growth of diabetic rats. 258 35

The effects of streptozotocin-induced diabetes on weight gain, bone growth and GH secretion have been studied in conscious chronically cannulated male rats. In addition to the classic diabetic symptoms (hyperphagia, polydipsia, polyuria, glycosuria and hyperglycaemia), the slow body weight gain (0.95 +/- 0.5 compared with 2.63 +/- 0.5 g/day in non-diabetic controls) was associated with a reduction in bone growth (from 162 +/- 9 to 48 +/- 4 microns/day) and a reduced pituitary GH content (from 1.5 +/- 0.2 to 0.6 +/- 0.06 mg/gland). Serial blood sampling during the day or overnight showed that the normal male episodic GH secretory pattern was obliterated in the diabetic animals. The constant osmotic stimulation of hyperglycaemia and high fluid turnover was reflected in a significant reduction in pituitary oxytocin and arginine vasopressin (AVP) stores. Intravenous insulin infusions (67-1340 pmol/h for 4 or 7 days) caused a large initial weight gain (greater than 20 g in 2 days) followed by a slower increase, and stimulated tibial bone growth (to 100 +/- 16 and 126 +/- 8 microns/day after 4 or 7 days respectively). Insulin infusion for 7 days also increased pituitary GH content (to 1 +/- 0.15 mg/gland), and the normal episodic GH secretory pattern returned. Intravenous infusions of insulin which reduced, but did not completely normalize, blood glucose levels, allowed the resumption of growth and pulsatile GH secretion. Continuous infusion of recombinant human insulin-like growth factor-I (hIGF-I) at 1110 pmol/h for 54 h also caused a large initial rise in body weight in diabetic rats (17.1 +/- 1.6 compared with 7.5 +/- 2.8 g in saline-infused controls) due primarily to increased fluid retention. This effect of hIGF-I occurred without any significant changes in pituitary GH, AVP, oxytocin, blood glucose or bone growth over this short-term infusion, nor was there any obvious effect on spontaneous GH secretion, monitored over the entire infusion period. We conclude that the diabetic rat is not a good model to study growth stimulation by short-term insulin or IGF-I treatments because the insulin-like effects of these peptides obscure their specific growth-promoting activities in this model.
 ...
PMID:Growth hormone and growth in diabetic rats: effects of insulin and insulin-like growth factor-I infusions. 268

This study examines the effect of experimental diabetes on the release of rat insulin-like growth factor I (rIGF-I) and its binding protein (IGF-BP) by adult rat hepatocytes in primary culture. Rats treated with streptozotocin (75 mg/kg) had decreased serum rIGF-I values of 0.37 +/- 0.04 U/ml compared to 1.06 +/- 0.04 in age-matched untreated rats (1 U = 770 ng human IGF-I). Concomitant decreases in hepatocyte production rates for rIGF-I (15% of the rate in cells from normal rats) and IGF-BP (30% of normal) were also observed for hepatocytes isolated from diabetic rats. Insulin replacement therapy (1.2 U/day) for 3-4 days normalized serum rIGF-I levels (0.92 +/- 0.07 U/ml) and increased rIGF-I production by isolated hepatocytes to 67% the rate of normal cells and IGF-BP production to 70% normal. Treatment of streptozotocin-treated rats with rGH (150 micrograms/day) in vivo for 7 days failed to increase serum rIGF-I levels or hepatocyte production of rIGF-I. Insulin in vitro (3 X 10(-7) M) increased rIGF-I release by hepatocytes from nondiabetic rats, but had no effect on cells from diabetic animals, suggesting that factors other than insulin are required to maintain rIGF-I synthesis in diabetes. Serum rIGF-I levels showed a strong correlation with hepatocyte rIGF-I production in the animals used in this study. However, calculation of circulating rIGF-I half-life based on these values showed a 2-fold higher half-life in diabetic rats (7.91 +/- 1.58 h) and rGH-treated diabetic rats (7.52 +/- 1.25 h) than in nondiabetic (2.99 +/- 0.35 h) and insulin-treated diabetic animals (3.85 +/- 0.36 h). This suggests that the rate of clearance of circulating rIGF-I may be slower in diabetic animals.
 ...
PMID:Production of insulin-like growth factor I and its binding protein in rat hepatocytes cultured from diabetic and insulin-treated diabetic rats. 294 14

The acute metabolic effects and receptor binding of insulin-like growth factors (IGFs) I and II were studied in human adipose tissue. The IGFs inhibited fat cell glycerol release and stimulated adipocyte 3-O-methylglucose transport and adipose tissue glucose oxidation as effectively as did insulin, but the biological potencies of the IGFs, on a molar basis, were 600-1000 times less than that of insulin. The insulin dose-response curve for antilipolysis gradually shifted to the left in the presence of submaximally and maximally effective IGF-I concentrations, whereas no additive response was found when fat cells were incubated with maximally effective concentrations of insulin and the IGFs. Adipocyte [125I]IGF-I and -II binding was low and was not inhibited by excess unlabeled IGF. In contrast, IGF-I inhibited [125I]insulin binding with a molar potency 1600 times lower than that of native insulin. In adipose tissue segments obtained from patients with untreated noninsulin-dependent diabetes mellitus, IGF-I and insulin inhibited glycerol release in a normal way. Conversely, neither insulin nor IGF-I increased the rate of glucose oxidation significantly above the nonhormone-stimulated level. We conclude that human fat cells lack specific cell surface IGF-binding sites. However, the IGFs definitely produce acute insulin-like effects in the human adipocyte, which seems to be mediated via the insulin receptor.
 ...
PMID:Studies of acute effects of insulin-like growth factors I and II in human fat cells. 295 92

Chicken embryos are a suitable model for studying the role of insulin, insulin-like growth factors I and II (IGF-I and IGF-II), and their receptors in embryogenesis. We show that plasma membranes from heart, liver, and limb buds, as reported earlier for brain, each have a distinct developmental profile for insulin receptors and type I IGF receptors. In heart and limb buds, IGF binding is higher than insulin binding, but in liver, insulin receptors dominate. Expression of these receptors is, therefore, developmentally regulated and tissue specific. The wide distribution of high-affinity receptors capable of mediating insulin and IGF actions in early organogenesis further supports the possible importance of this family of peptides for differentiation and growth in vertebrates. In all chicken embryo tissues studied, both IGF-I and IGF-II appeared to bind to a type I IGF receptor. We have not detected a receptor with the peptide binding and structural characteristics of the mammalian type II IGF receptor. The type II receptor was absent in embryos, liver from newly hatched chicks, and adipocytes from older chicks, which suggests that the chicken may lack this subtype of IGF receptor.
Diabetes 1988 May
PMID:Developmental regulation of insulin and type I insulin-like growth factor receptors and absence of type II receptors in chicken embryo tissues. 296 86

Endothelial cells form the intimal lining of the entire vascular system. The vascular endothelium is continuously and directly bathed by components of the bloodstream and represents the initial fixed anatomical surface with which these components come in contact. In the past decade, the methodologies for studying endothelial cell functions have markedly advanced, enabling direct and detailed study of the vascular endothelium. From such studies, it is now apparent that the vascular endothelium represents an extraordinarily complex network of cells demonstrating a multitude of distinct anatomic, metabolic, and immunologic properties critical to such processes as angiogenesis, atherosclerosis, thrombosis, neoplasia, and a variety of metabolic disorders including homocystinuria and diabetes mellitus. This report will focus on the interactions of insulin and the insulin-like growth factors (IGFs) with vascular endothelium, based on studies with cultured endothelial cells, isolated microvessels, and perfused organ systems. Data will be presented relevant to the following concepts: (1) endothelial cells, in culture and in vivo, have specific receptors for insulin, IGF-I, and IGF-II; (2) insulin, IGF-I, and IGF-II have both distinct and overlapping functions in cultured endothelial cells; (3) cultured endothelial cells process receptor-bound insulin, IGF-I, and IGF-II, by distinct processes; (4) in vivo, capillary endothelial receptors are integrally involved in the transport of intact insulin to subendothelial sites of insulin action; and (5) vascular endothelium has specialized cellular features that are likely to contribute to the unique interactions of endothelial cells with insulin and the IGFs.
 ...
PMID:Insulin, insulin-like growth factors, and vascular endothelium. 297 48

Insulin and insulin-like growth factors (IGFs) have been implicated in the pathogenesis of diabetic retinopathy and peripheral vascular complications. Previously, we have shown that retinal capillary endothelial cells responded to insulin and IGFs for metabolic and growth effects, whereas aortic endothelial cells were not responsive. In contrast, vascular supporting cells from both retinal capillaries (i.e. pericytes) and aorta (i.e. smooth muscle cells) responded equally to insulin, IGF-I, and IGF-II. The structure and ligand specificities of the receptor for these peptides were studied by covalently cross-linking 125I-labeled peptide hormones to their respective receptors using disuccinimidyl suberate, followed by polyacrylamide gel electrophoresis and autoradiography. The binding subunit of the insulin receptor, alpha-subunit, for all cell types was found to have a mol wt 145,000 under reduced conditions. Labeling of this band was inhibited by 10(-9) M insulin, antiinsulin receptor antibodies, and 10(-8) M IGF-I, but not by multiplication-stimulating activity (IGF-II). The beta-subunit of the insulin receptor in endothelial cells was identified by its ability to be autophosphorylated when stimulated by insulin and was found to have a mol wt of 99,000. Covalent cross-linking of IGF-I to its receptor revealed a mol wt of 145,000, similar to that of insulin receptor, except that IGF-I was 100-fold more potent than insulin in competing with [125I]IGF-I for binding. [125I]IGF-II in all cells was cross-linked to receptor with mol wt of 260,000 and 230,000 under reduced and nonreduced conditions, respectively. IGF-I competed weakly with [125I]IGF-II, whereas insulin was ineffective. [125I]IGF-II also bound to the band with alpha mol wt of 135,000, which was inhibited by insulin, IGF-I, and IGF-II. In summary, receptors for insulin, IGF-I, and IGF-II on cells from micro- and macrovessels are biochemically similar to those in other cells. Interestingly, the finding of large numbers of IGF-I and IGF-II receptors on endothelial cells suggests that these growth factors play a physiological role and are involved in vascular complications associated with diabetes.
 ...
PMID:Characterization of the receptors for insulin and the insulin-like growth factors on micro- and macrovascular tissues. 299 Aug 69


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