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

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

We investigated the effect of improving glycemic control on serum concentrations of insulin-like growth factors I and II (IGF-I and IGF-II). In 22 adults followed during an intensive home glucose monitoring program for 6 mo, no effect of improving control was seen on either IGF-I or IGF-II. Similar results were obtained in young diabetic children less than 10 yr of age and in diabetic adolescents with detectable puberty before entering the study. In older diabetic children without evidence of puberty before treatment (Tanner prepubertal stage 1), initial IGF-I concentrations were low, but increased during establishment of glycemic control. Puberty developed during therapy in this latter group. Our data do not support a "global" effect of glycemic control on serum IGF-I in diabetic patients. Increases of IGF-I with better glycemic control appear most likely to occur when the metabolic consequences of diabetes have suppressed normal pubertal increases of IGF-I. IGF-II concentrations were unaffected by glycemic control in all subjects.
Diabetes 1984 Aug
PMID:Effect of glycemic control on serum insulin-like growth factors in diabetes mellitus. 637 1

Early renal changes in type I diabetes are characterized by an increase in renal size, glomerular volume, and kidney function, and later by development of mesangial proliferation, accumulation of glomerular extracellular matrix, and increased urinary albumin excretion (UAE). Growth hormone (GH) and insulin-like growth factors (IGFs) have a long and distinguished history in diabetes mellitus, with possible participation in the development of long-term complications. In experimental diabetes in dwarf rats with isolated GH and IGF-I deficiency, a slower and lesser renal and glomerular hypertrophy is observed as compared with diabetic control animals with intact pituitary. Furthermore, diabetic dwarf rats with a diabetes duration of 6 months display a smaller increase in UAE, indicating that GH and IGF-I may be involved in the development of diabetic kidney changes. In line with this, administration of octreotide to streptozotocin (STZ)-diabetic animals with normal pituitary inhibits initial renal growth without affecting blood glucose levels, and 6 months' administration of octreotide to diabetic rats reduces long-term renal/glomerular hypertrophy and UAE. In addition, the initial increase in renal size and function in experimental diabetes is preceded by an increase in renal IGF-I, IGF-binding proteins (IGFBPs), and IGF-II/mannose-6-phosphate receptor (IGF-II/Man-6-P receptor) concentration. Finally, specific changes occur in renal GH-binding protein (GHBP) mRNA, IGF-I receptor mRNA, and IGFBP mRNA expression in long-term diabetes. In conclusion, the knowledge we have today indicates that GH and IGFs, through a complex system consisting of GHBP, IGFs, IGF receptors, and IGFBPs, may be responsible for both early and late renal changes in experimental diabetes.
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PMID:The role of growth hormone, insulin-like growth factors (IGFs), and IGF-binding proteins in experimental diabetic kidney disease. 747 14

Maternal diabetes is associated in humans and rats with an increased risk for fetal growth abnormalities and malformations. Therefore, the effect of maternal diabetes on expression of genes that regulate fetal growth and differentiation is of considerable interest. Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs). Postnatal expression of a subset of the IGFs and IGF binding proteins (IGFBPs) has been demonstrated to be regulated in response to diabetes and other metabolic conditions. We used in situ hybridization to analyze the effect of maternal diabetes, induced by streptozotocin (STZ) prior to mating, upon prenatal rat IGF and IGFBP mRNA expression. At gestational day (GD) 14, the most striking effect of maternal diabetes on fetal IGF/IGFBP gene expression was a marked increase in the abundance of IGFBP-1 mRNA within the liver primordia of fetuses isolated from diabetic dams compared to age-matched controls. This upregulation cannot be entirely due to the approximately one-half-day delay in fetal development (based on limb bud staging) associated with maternal diabetes, as there was no gross difference in the level of IGFBP-1 mRNA between GD13 and GD14 control fetal livers. In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes. These data are consistent with the hypothesis that IGFBP-1 produced within the fetal liver and secreted into fetal circulation may play a role in regulating rat fetal growth.
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PMID:Effects of maternal diabetes on fetal expression of insulin-like growth factor and insulin-like growth factor binding protein mRNAs in the rat. 749 May 44

In the present study we have 1) assessed how differences in insulin and GH status between obese patients with noninsulin-dependent diabetes mellitus (NIDDM) and healthy obese (OB) and nonobese (NOB) subjects are associated with different responses of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) to fasting, and 2) determined whether the IGF-I response to fasting in healthy subjects is secondary to changes in IGFBP-3. In patients with NIDDM, there was a lack of response of serum IGF-I concentrations to 4 days of fasting, contrasted with the significant decrease in IGF-I concentrations in NOB subjects (37%; P < 0.001) and the delayed and attenuated decrease in OB subjects (23%; P < 0.01). Insulin and the insulin-regulated IGFBP-1 were also unchanged during fasting in NIDDM, whereas insulin was decreased and IGFBP-1 was increased in both NOB and OB subjects. Insulin-resistant NIDDM patients, with high basal glucose and insulin, normal IGFBP-1, and low GH, had decreased prefasting serum IGF-I concentrations, similar to the values in fasted body mass index- and age-matched OB subjects. IGFBP-3, the major determinant of the IGF-I turnover rate in serum, was unchanged by fasting, as determined by RIA and Western ligand blot analysis. In accordance, no induction of IGFBP-3 proteolytic activity by fasting could be demonstrated. Serum IGF-II concentrations were also unchanged by fasting. Basal immunoreactive IGFBP-3 levels did not differ among the groups, whereas IGFBP-3 by Western ligand blot analysis was decreased in NIDDM in accordance with the finding of increased IGFBP-3 proteolysis in NIDDM. In conclusion, 1) differences in GH status and modulation of GH induction of IGF-I by insulin resistance could contribute to low basal IGF-I levels and lack of a IGF-I response to fasting in patients with NIDDM; and 2) the turnover rate of IGF-I in serum, which is largely determined by IGFBP-3, is not likely to be altered by short term fasting, suggesting that the decrease in serum IGF-I concentrations is a result of decreased IGF-I production.
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PMID:Fasting affects serum insulin-like growth factors (IGFs) and IGF-binding proteins differently in patients with noninsulin-dependent diabetes mellitus versus healthy nonobese and obese subjects. 751 73

Insulin-like growth factor-I (IGF-I) has been inversely associated with low-density lipoprotein (LDL) cholesterol in normal women with slightly elevated cholesterol levels and hypothyroid women. More than 95% of IGF-I circulates bound to binding proteins (IGFBPs); of these IGFBP-1 is of particular interest as it is inversely regulated by insulin and is thought to inhibit the action of IGF-I and IGF-II. We examined the relationship between IGFBP-1 and LDL cholesterol in 41 healthy adult subjects. LDL cholesterol correlated with the body mass index (r = 0.40, P < 0.01), sex (r = 0.51, P < 0.001) and IGFBP-1 levels (r = 0.36, P < 0.02). LDL cholesterol did not correlate with age (r = 0.25, P = not significant) or IGF-I (r = 0.06, P = not significant). Upon multivariate regression analysis, sex, body mass index and IGFBP-1 were all independent predictors of LDL cholesterol (all P < 0.05). Elevated IGFBP-1 levels have been associated with an inhibition of serum IGF-I bioactivity in children with insulin-dependent diabetes. IGFBP-1 also appears to inhibit IGF-I hexose-stimulated uptake. IGFBP-1 may also be inhibiting the effect of IGFs on the cellular metabolism of LDL cholesterol.
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PMID:Insulin-like growth factor-binding protein-1 is correlated with low density lipoprotein cholesterol in normal subjects. 751 6

There is a growing body of evidence that the insulin-like growth factors (IGF-I and IGF-II) are dynamically involved in the regulation of glucose homeostasis, with one of their binding proteins, IGFBP-1, playing a counterregulatory role. The IGFs are structurally and functionally related to insulin and in the circulation they represent a huge hypoglycemic potential which is buffered by their association with the IGFBPs. The predominant IGFBP in serum, IGFBP-3, is able to form a high molecular weight complex with the IGFs and this complex is retained in the circulation and appears to act as a reservoir of IGFs. The IGFs and IGFBP-3 are regulated in the long term by changes in nutritional status. In contrast, IGFBP-1 is acutely regulated in a manner similar to glucose counterregulatory hormones. IGFBP-1 is able to block the insulin-like actions of the circulating IGFs and when administered alone as a bolus infusion causes an increase in blood glucose levels. There is recent evidence that more IGFs are available for an endocrine glucoregulatory role than indicated by estimates of steady-state 'free' IGF levels. The IGF/IGFBP system may thus play a complementary role to insulin and the classical counterregulatory hormones in the control of blood glucose.
Diabetes Res Clin Pract 1994 Feb
PMID:Role of the insulin-like growth factors in the endocrine control of glucose homeostasis. 751 50

It has been suggested that recombinant human IGF-I (rhIGF-I) is a potential therapeutic agent in diabetes mellitus. It is known to have glucose-lowering effects in normal individuals, in patients with non-insulin-dependent diabetes (NIDDM) and in extreme insulin-resistant states. IGF-binding proteins (IGFBPs) have the potential to affect the biological activity of rhIGF-I. We have studied the effect of infused rhIGF-I on IGFBP-1 and IGFBP-3 in a patient with Mendenhall's syndrome, a rare insulin-resistant state. During an infusion of 20 mg rhIGF-I, glucose concentrations fell from 44.1 +/- 7.2 to 31.5 +/- 7.2 (S.E.M.) mmol/l (P = 0.001), and insulin and C-peptide levels fell from 920 +/- 62 to 542 +/- 45 mU/l (P = 0.008) and 5466 +/- 633 to 3071 +/- 297 pmol/l (P = 0.02) respectively. Significant lowering of phosphate, magnesium and alkaline phosphatase concentrations was also noted. IGF-I levels rose from 48 +/- 10.2 to 410 +/- 50.1 micrograms/l (P = 0.001), and those of IGF-II fell from 279.8 +/- 8.3 to 104.3 +/- 7.9 micrograms/l (P = 0.001). IGFBP-1 concentrations did not significantly change during the infusion but those of IGFBP-3 increased from 1655 +/- 127 to 2197 +/- 334 micrograms/l (P = 0.002), despite a significant fall in GH concentrations from 10.7 +/- 2.6 to 4.1 +/- 1.1 mU/l (P = 0.007), suggesting that IGFBP-3 regulation is also IGF-I-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) and IGFBP-3 to IGF-I treatment in severe insulin resistance. 751 62

Although patients with diabetic retinopathy have been reported to have elevated vitreal IGF-I levels, it is not known whether diabetes also affects the levels of vitreal IGF binding proteins (IGFBPs) which control IGF's bioavailability. To address this issue, vitreal IGFBP levels were assayed in human diabetics, rats with streptozotocin-induced diabetes and galactose-fed dogs with diabetic-like retinopathy. Using 125I-IGF-II ligand blots, it was found that human diabetics have a 4-fold increase in vitreal IGFBP levels. Also, western blots on human diabetic vitreous reveal increased levels of IGFBP-2 and proteolytic fragments of IGFBP-3. IGF binding assays on vitreous from streptozotocin-treated rats (three months in duration) also indicate a 5-fold increase in IGF binding activity. IGF ligand blots using vitreous from rats with a shorter duration of diabetes (one month) show a 63% increase in IGFBP binding and a marked decrease in serum IGFBP binding. IGF ligand blots and IGFBP-2 and -4 western blots using vitreous from galactose-fed dogs with diabetic-like retinopathy exhibit a 6-fold increase in vitreal IGFBPs. The observation that vitreal IGFBPs are elevated in diabetic humans and rats without overt retinopathy suggests that these increases are not the result of a preexisting end-stage retinopathy but rather are an early ocular event in the diabetic process. Increases in vitreal IGFBPs thus could participate in the proliferative aspects of diabetic retinopathy by virtue of their putative intrinsic bioactivity or their capacity to alter IGF bioavailability.
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PMID:Vitreal insulin-like growth factor binding proteins (IGFBPs) are increased in human and animal diabetics. 752 30

Insulin-dependent diabetes can be associated with low insulin-like growth factor-I (IGF-I) levels despite normal or even high GH secretion. The basis of the diabetic abnormalities in GH-IGF dynamics that contribute to insulin resistance and impaired fuel metabolism are not well understood. To further investigate these matters, this study evaluated baseline IGF system parameters and responses to recombinant human IGF-I in four diabetic adolescents and six pubertal stage-matched controls. Spontaneous overnight and arginine-stimulated GH secretion, insulin, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured before, during, and after daily 10-h sc infusions of saline or IGF-I (20 micrograms/kg.h). Baseline overnight GH secretion and IGFBP-1 and -3 levels were not significantly different in the two groups, but IGF-I levels were significantly lower and IGF-II levels were higher in diabetic subjects. IGF-I infusion produced a 3-fold increase in serum IGF-I levels and a reciprocal profound reduction in IGF-II levels in both groups. IGFBP-1 levels increased dramatically in diabetics and modestly in normal subjects in response to IGF-I infusion, but IGFBP-3 levels were not significantly altered. Spontaneous overnight and arginine-stimulated GH secretion were suppressed by about 50% in both groups after IGF-I infusion. Insulin requirements were substantially reduced in diabetics receiving IGF-I, and insulin secretion was suppressed in normal subjects, with no evidence of a change in insulin half-life. Blood glucose remained stable in both groups throughout saline and IGF-I infusions, and no hypoglycemia or other adverse effect occurred during IGF-I infusions. Further studies are necessary to determine whether the addition of IGF-I to insulin replacement therapy may stably reduce the insulin requirement, maintain normal GH levels, and perhaps achieve better metabolic and anabolic balance in the treatment of insulin-dependent diabetes.
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PMID:The effects of subcutaneous insulin-like growth factor-I infusion in insulin-dependent diabetes mellitus. 752 24


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