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)

We have determined the level of phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) in serum during two catabolic states: diabetes mellitus and trauma. Human sera were incubated with [125I]IGF-I for 2 h followed by non-denaturing PAGE. [125I]IGF-I/IGFBP-1 complexes from serum co-migrated with a pure p4IGFBP-1 standard. Complex formation was specifically inhibited by unlabeled IGF-I. The migration of IGF-I/pIGFBP-1 complexes was retarded by IGFBP-1 antibodies, but not by antibodies against IGFBP-2 or IGFBP-3. Sera from three severely traumatized patients had up to 12-fold more pIGFBP-1 than sera from age-matched controls. The level of pIGFBP-1 was reduced in all three patients upon hospital discharge. Sera from three patients with insulin dependent diabetes mellitus (IDDM) and severe ketoacidosis (DKA) had more pIGFBP-1 than controls. Administration of insulin to DKA patients lowered the level of pIGFBP-1. The present study shows that IGFBP-1 exists as a free, high affinity, phosphorylated form in vivo during two catabolic states.
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PMID:Phosphorylation of insulin-like growth factor binding protein-1 in patients with insulin-dependent diabetes mellitus and severe trauma. 751 91

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

Nephropathy, one of the major complications of diabetes mellitus, is characterized by an early increase in kidney size. In experimental models of diabetes, this event is preceded by a rapid and transient rise in kidney IGF-I levels, at least in adult animals. Since diabetes-associated renal changes are uncommon in young patients, we investigated the early changes in the components of the IGF system following induction of diabetes in prepubertal and postpubertal rats. The rationale for this study was the evaluation of potential differences which could lead to kidney complications only at adult stages. Unlike the situation in the postpubertal kidney, in which there was a transient accumulation of extractable IGF-I 24-48 h after streptozotocin (STZ) administration, there was a decrease of approximately 12-fold in the level of IGF-I in the prepubertal kidney over the same period of time. Paradoxically, kidney IGF-I mRNA levels were reduced by approximately 50% in the postpubertal rat 24 h after STZ treatment, whereas in the prepubertal kidney IGF-I mRNA levels were unaltered. Furthermore, the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding to kidney membranes of postpubertal diabetic rats were similar to the levels in control kidneys. On the other hand, both the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding were increased (approximately 2.5-fold (after 24 h) and approximately 3-fold (after 48 h) respectively) in prepubertal animals. In addition, increased expression of IGF-binding protein (IGFBP)-1 mRNA was seen early in diabetes in both pre- and postpubertal rats. The results of this study suggest that the transient accumulation of IGF-I in the kidney of the postpubertal diabetic rat may not be due to an increase in the local synthesis of IGF-I, but rather to an increase in IGF-I uptake from the circulation due to non-membrane-associated IGFBP-1. The lack of accumulation of IGF-I in the prepubertal kidney probably reflects the approximately 10-fold lower levels of circulating IGF-I in young as compared with adult diabetic rats.
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PMID:Differential accumulation of insulin-like growth factor-I in kidneys of pre- and postpubertal streptozotocin-diabetic rats. 752 Feb 45

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

The acid-labile subunit (ALS) and insulin-like growth factor (IGF)-binding protein-3 are glycoproteins that form a complex carrying about 90% of the circulating IGFs. This study investigates the regulation of ALS expression by Northern hybridization, and serum ALS levels by RIA, in the rat. Northern analysis of ALS messenger RNA (mRNA) from adult rat brain, heart, lung, muscle, spleen, testis or ovary, kidney, and liver showed a liver-specific predominant 2-kilobase transcript. The steady state abundance of rat ALS mRNA was greatly reduced in neonatal and weanling liver compared to adult liver, with an age dependence similar to that of rat serum ALS levels. Fasting for 24 or 48 h decreased serum IGF-I and ALS levels, but not hepatic ALS mRNA. Streptozotocin-diabetic rats, untreated or treated with human GH for 5 days, had significantly decreased serum ALS levels and liver ALS mRNA abundance. Insulin treatment normalized serum ALS without fully restoring ALS mRNA. Dexamethasone, an inhibitor of ALS synthesis by hepatocytes, significantly reduced both serum ALS and hepatic ALS mRNA. The discrepancies between hepatic expression and serum ALS levels in fasting and diabetes point to a complex regulatory mechanism in which events at the translational level or later may be as important as regulation of gene expression or mRNA stability.
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PMID:Regulation in vivo of the acid-labile subunit of the rat serum insulin-like growth factor-binding protein complex. 752 31

The present study was undertaken to investigate the metabolic regulation of insulin-like growth factor binding proteins (IGFBPs) gene expression in muscles from diabetic or fasted rat. The messenger RNA (mRNA) levels for IGFBP-2 and -4 were analysed by solution hybridization in heart, skeletal and smooth muscle and liver from fasted (3 days) and refed (6, 12, 24, 72 h) rats and rats made diabetic with streptozotocin. In aortic intima-media, the mRNA levels for IGFBP-2 and -4 were decreased by diabetes or fasting and were restored gradually by refeeding. The response of IGFBP-4 mRNA to diabetes appeared two days after injection of streptozotocin, while a significant decrease of IGFBP-2 mRNA was found after a diabetes duration of two weeks. Both diabetes and fasting decreased IGFBP-4 mRNA levels in heart muscle and skeletal muscle and refeeding restored mRNA for IGFBP-4 to normal level. IGFBP-2 mRNA was undetectable in heart muscle and skeletal muscle. In liver IGFBP-4 mRNA was abundantly expressed. It was slightly but significantly decreased by fasting and approached normality with refeeding, while no change was found in diabetic liver. In contrast, liver IGFBP-2 mRNA was much lower in amount than IGF-I mRNA and IGFBP-4 mRNA and was sharply elevated by fasting, and decreased by refeeding. In conclusion, 1) both IGFBP-2 and -4 mRNA in various tissues are regulated by diabetes or fasting; 2) the mRNA for IGFBP-2 is metabolically regulated in a discordant, organ-specific manner.
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PMID:Differential regulation of insulin-like growth factor binding protein-2 and -4 mRNA in muscle tissues and liver by diabetes or fasting. 753 Feb 85

The putative effects of diabetes and metabolic control on circulating levels of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) remain controversial. In the present study, serum levels of IGF-I and IGF-II and IGFBP-1, -2, and -3 were measured in 58 patients (age, 0.8-17 yr) with treated (51 subjects) or untreated (7 subjects) insulin-dependent diabetes mellitus (IDDM) and were compared with the levels in normal subjects. In the untreated patients IGF-I and IGF-II were decreased as compared with the healthy controls. In the treated diabetics IGF-I and IGF-II were reduced; IGFBP-2 (only in prepubertal subjects) and IGFBP-3 were increased. Furthermore, age-adjusted values of IGF-I, IGF-II, and IGFBP-3 were lower in prepubertal than in pubertal patients. Regression analysis revealed a negative correlation between hemoglobin (Hb)A1c and standard deviation scores (SDS) of IGF-I and a positive association between HbA1c and IGFBP-1 SDS or IGFBP-2 SDS. In the treated patients HbA1c was positively related to IGFBP-1 SDS and IGFBP-2 SDS when applying simple regression analysis and to IGFBP-2 SDS when using a multiple regression model. Strong correlations were observed between height SDS and IGF-I SDS, IGF-II SDS, and IGFBP-3 SDS in prepubertal subjects who had had IDDM for at least 2 yr, but not in adolescents. Such correlations have also been found in healthy children and adolescents. In conclusion; 1) IDDM is associated with alterations of the IGF-IGFBP system, which are partially accounted for by differences in metabolic control and pubertal status; 2) the lower plasma concentrations of serum IGF-I may play a role in the pathogenesis of growth impairment of poorly controlled prepubertal, but not pubertal, children and adolescents with IDDM; and 3) in addition, a potential role of the altered IGF-IGFBP system for the development of diabetic late complications is hypothesized.
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PMID:Insulin-like growth factor (IGF)-I and -II and IGF-binding proteins-1, -2, and -3 in children and adolescents with diabetes mellitus: correlation with metabolic control and height attainment. 753 2

To further characterize the mechanism of impaired growth in children with insulin-dependent diabetes mellitus, we examined the serum components of the insulin-like growth factor (IGF) system in 11 children with new-onset insulin-dependent diabetes mellitus and followed the effect of insulinization on the IGF system longitudinally 1 day, 1 week, and 1 month after starting insulin treatment. Before insulin therapy, serum IGF-I, IGF-II, IGF-binding protein-3 (IGFBP-3), and GH-binding protein (GHBP) levels were significantly decreased, whereas IGFBP-1 and cortisol were significantly increased in diabetic children compared to those in an age-, sex-, and stage of puberty-matched control group. Random serum GH concentrations did not differ significantly. The alterations in the IGF system reversed with insulin therapy in a sequential manner. IGFBP-1 fell rapidly and was comparable to control values within 24 h after insulin treatment. IGF-I rose 1 week after treatment, reaching levels comparable to those in controls and continued to rise through 1 month of treatment. IGF-II, IGFBP-3, and GHBP showed a slower pattern of change, with their levels reaching control values only 1 month after the start of insulin treatment. Improvement in glycemic control, as determined by a change in hemoglobin-A1c, correlated positively with improvement in IGF-I, IGF-II, IGFBP-3, GHBP, and weight gain after 1 month of insulin therapy. These data are consistent with the hypothesis that changes in the IGF system in the insulinopenic state are similar to those during nutritional deprivation and may serve to minimize IGF's anabolic actions. The decreases in IGF-I, IGF-II, and IGFBP-3 may in part be due to a decrease in the GHBP/receptor. However, the observation that an increase in serum IGF-I was observed earlier than an increase in GHBP and without a significant change in serum GH suggests a direct stimulatory effect of insulin on liver IGF-I production or reversal by insulin of some postreceptor defect in GH action independent of GHBP.
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PMID:Effect of insulin on the insulin-like growth factor system in children with new-onset insulin-dependent diabetes mellitus. 753 5

Recent studies have shown that the renal synthesis of insulin-like growth factor binding proteins (IGFBPs) is altered in insulin-deficient diabetes mellitus, suggesting that these changes may be implicated in the alterations in renal function and morphology that accompany diabetes. To investigate the time course and the precise cellular distribution of changes in IGFBP expression, we used quantitative in situ hybridization to analyze renal IGF-I and IGFBP-1 to -5 messenger RNA (mRNA) localization and levels from 2 days to 6 months after the onset of streptozotocin-induced diabetes. There was an immediate sharp decline in IGF-I mRNA levels in the outer medulla that persisted for up to 3 months and a much smaller reduction in IGF-I mRNA levels in the medullary thick ascending limbs (MTALs). In nondiabetic animals, IGFBP-1 mRNA is most abundant in the MTALs. Immediately after the induction of diabetes, however, there was a greater than 2-fold increase in cortical IGFBP-1 mRNA and a 75% decrease in IGFBP-1 mRNA in MTALs. These changes persisted for up to 6 months in the diabetic animals. In contrast, IGFBP-5 mRNA levels were increased in the outer medulla and decreased in the cortex of diabetic kidneys. No significant changes in renal IG-FBP-2 mRNA levels or distribution were noted, and changes in IG-FBP-3 and -4 mRNA levels were subtle. In summary, streptozotocin-induced diabetes is associated with very prominent and complex alterations in renal IGF system gene expression, including robust increases in cortical IGFBP-1 and profound decreases in cortical IG-FBP-5 mRNA and medullary IGF-I mRNA levels. The divergent changes in IGFBP-1 and -5 mRNA levels in cortex vs. outer medulla indicate that regulation of IGFBP mRNA levels is quite complex.
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PMID:Expression of insulin-like growth factor binding proteins in the rat kidney: effects of long-term diabetes. 753 58


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