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

It is yet unknown whether the impaired nutritional status of streptozotocin-induced diabetic rats influences changes in levels of insulin-like growth factor-I (IGF-I) in this experimental model of diabetes. To explore this possibility, simultaneous studies were undertaken of rats made diabetic by streptozotocin (75 mg/kg body wt, intraperitoneally) and undernourished control rats with similar somatic growth rate (determined by body weight gain), in comparison with normal controls. Serum IGF-I levels were diminished in the untreated diabetic and undernourished control animals, but more so in the diabetic group. Lung IGF-I levels (per lung and per lung DNA) and DNA contents were diminished to similar degrees in the untreated diabetic animals and the undernourished control group. Lung dry weights of the diabetic rats were greater than those of the undernourished control group, such that lung IGF-I/100 mg tissue dry wt in the former was significantly lower than in the latter group. Insulin treatment of the diabetic rats restored their body weights, serum and lung IGF-I levels, and DNA contents to normal control values. Lung IGF-I levels in the diabetic rats correlated strongly with serum glucose (r = .75) and body weight (r = .79), and moderately with lung weight (r = .43) and lung DNA (r = .58). These findings suggest that the diminished lung IGF-I levels in streptozotocin-induced diabetes may be related to the impaired nutritional status and/or somatic growth of the experimental animals, and that this relationship may be responsible, at least in part, for the diminished lung cellular proliferation observed in experimental diabetic animals.
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PMID:Diminished levels of insulin-like growth factor-I in lungs in streptozotocin-induced diabetes: relation to nutritional status and growth. 818 51

Endothelial cells are likely to play an important role in the development of diabetic vascular diseases, since they are exposed directly to the abnormal circulating metabolites of diabetes and may be easily damaged early in the natural course of vascular complications. In this study, aortic endothelial cells were cultured from diabetic BB rats. Their binding and internalization of insulin-like growth factor-I (IGF-I) were measured. IGF-I binding was higher in cells of diabetic rats than of control rats at both 37 degrees C (4.5% +/- 1.6% v 2.74% +/- 0.9% per mg protein, P < .05) and 4 degrees C (20.6% +/- 5.6% v 13.7% +/- 4.6% per mg protein, P < .01). Internalization of IGF-I also increased (1.62% +/- 0.2% v 0.74% +/- 0.15% of total count at 37 degrees C after 60 minutes, P < .05). Cross-linking studies showed that in cells from diabetic rats, the major band of 140 kd corresponding to the alpha-subunit of the IGF-I receptor increased in density by 50% compared with those from control rats. The IGF-I-stimulated tyrosine kinase activity (TKA) of partially purified receptor from cells of diabetic rats, measured using poly-glu-tyr as substrate, was normal. Since the biological effects of IGF-I are initiated by its binding to the IGF-I receptor, which is able to transduce mitogenic and metabolic signals, our results support the hypothesis that the IGF-I receptor is involved in the development of diabetic vascular complications.
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PMID:Insulin-like growth factor-I receptor increases in aortic endothelial cells from diabetic rats. 823 30

Early renal manifestations of type I diabetes include kidney enlargement, increased glomerular filtration rate, and renal plasma flow. These hemodynamic changes may be caused by a number of factors, including growth hormone and/or insulin-like growth factor-I (IGF-I). Streptozotocin-induced insulinopenic diabetes in rats represents a model of human type I diabetes and is associated with the early hemodynamic changes in the kidney seen in poorly controlled type I diabetic patients. These changes are preceded by an accumulation of IGF-I peptide in the kidney. Insulin-like growth factor-I is not locally produced, but rather accumulates from circulating IGF-I, trapped by increased levels of IGF-binding proteins, particularly IGF-binding protein-1. The hemodynamic effects, reproduced by infusions of recombinant human IGF-I in normal rats, may be blocked by co-infusion of a kinin-receptor antagonist, suggesting that at least one of the mechanisms involved is the kallikrein-kinin system. These studies strongly support the notion that the IGF system may play a role in early hemodynamic manifestations of the diabetic kidney. Whether these effects lead to long-term diabetic renal disease remains to be studied.
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PMID:The role of insulin-like growth factors in diabetic kidney disease. 823 20

Insulin-like growth factor-I (IGF-I) has been implicated as a possible mediator of renal hypertrophy after uninephrectomy and diabetes mellitus. Because renal hypertrophy is also a consequence of high protein intake, we studied the effect of varying concentrations of dietary protein on circulating levels and renal tissue content of IGF-I. Male Sprague-Dawley rats were fed isocaloric diets containing high (50%, HP), normal (20%, NP) or low (6%, LP) dietary protein for up to 14 days before they were killed. As expected, renal size (dry kidney weight) was greater in HP-fed rats and smaller in LP-fed rats when compared with NP-fed animals (HP, 1415 +/- 26 mg [p < 0.01 vs NP]; NP, 1148 +/- 27 mg; LP, 838 +/- 16 mg [p < 0.01 vs NP]), and most of the relative changes in kidney size occurred during the first week of ingestion of the experimental diet. Renal hypertrophy in the HP-fed animals was accompanied at day 3 by a significant rise in kidney tissue IGF-I that remained elevated at day 7 but had fallen to baseline values by day 14. The rise in renal IGF-I content in the HP-fed rat was accompanied by increases in circulating IGF-I on day 3 only. Both circulating and renal tissue IGF-I levels were suppressed in the LP-fed animals at 3, 7, and 14 days. These data confirm that varying dietary protein intake has profound effects on both circulating and renal IGF-I levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of dietary protein intake on renal growth: possible role of insulin-like growth factor-I. 824 81

Growth hormone (GH) and insulin have both mitogenic and metabolic actions. The growth-promoting effects of GH in vivo are thought to be mediated by insulin-like growth factor-I (IGF-I), whereas the metabolic effects of GH are thought to be either direct or mediated by factors other than IGF-I. In previous studies using HTLV-II-transformed T-lymphoblast cell lines established from normal individuals, we have shown that GH preincubation induces resistance to the growth-promoting (mitogenic) action of insulin. In this study, using T-cell lines from 3 American control subjects, 1 African control subject, and 1 African Pygmy (the latter previously shown to be resistant to the growth-promoting actions of both IGF-I and GH), we examined the role of local IGF-I in the mediation of GH-induced resistance to the mitogenic action of insulin. In these studies, we quantified the stimulation of T-cell colony formation in response to insulin in the presence and absence of either GH or IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1994 Jan
PMID:Growth hormone induces resistance to the mitogenic action of insulin through local IGF-I. Studies in normal and Pygmy T-cell lines. 826 19

Type 2 (non-insulin-dependent) diabetes mellitus is associated with increased glucose, insulin, total and VLDL-triglyceride, and often total and LDL-cholesterol levels which promote vascular disease. Recombinant human insulin-like growth factor-I which mimics many effects of insulin, decreased insulin, total and VLDL-triglyceride, and total and LDL-cholesterol levels in healthy man as well as glucose and insulin levels in Type 2 diabetic patients. We, therefore, investigated total and fractionated triglyceride and cholesterol levels, lipoprotein(a), non-esterified fatty acid, and apolipoprotein levels in eight Type 2 diabetic patients during five control, five treatment, and three wash-out days. They received a constant diet throughout and daily 2 x 120 micrograms insulin-like growth factor-I/kg s.c. during the treatment period. Fasting total and VLDL-triglyceride, total and LDL-cholesterol control levels were (mean +/- SD) 3.1 +/- 2.6, 1.3 +/- 1.0, 6.3 +/- 1.3, and 4.5 +/- 1.1 mmol/l and decreased to 1.6 +/- 0.8, 0.6 +/- 0.4, 5.0 +/- 1.0, and 3.5 +/- 1.1 mmol/l, respectively, on the last treatment day (p < 0.01). During therapy, fasting lipoprotein(a) levels and the postprandial area under the triglyceride curve decreased by 48 +/- 22 and 32 +/- 18% of control (p < 0.01), respectively. In conclusion, insulin-like growth factor-I lowered lipid levels in Type 2 diabetic patients directly or indirectly or both because of decreased glucose and insulin levels. Long-term trials would be of interest with respect to the cardiovascular risk in Type 2 diabetes and patients with hyperlipidaemia.
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PMID:Improvement of lipid profile in type 2 (non-insulin-dependent) diabetes mellitus by insulin-like growth factor I. 806 48

At puberty, elevated circulating GH concentrations are found, with a parallel increase in the levels of insulin-like growth factor-I (IGF-I). However, these hormonal changes are less well understood in children with insulin-dependent diabetes mellitus (IDDM) during the peripubertal years. Since the metabolic derangement is often associated with elevated circulating GH and diminished serum IGF-I levels, we sought to determine whether similar alterations occur in boys with IDDM. A multiple parameter deconvolution analysis was applied to serum GH concentrations measured at 20-min intervals for 24 h in 25 boys with IDDM. Subjects were divided into 3 pubertal groups, pre (n = 9), early (n = 8), and late (n = 11), according to Tanner stage. Glycosylated hemoglobin and body mass index-SD scores were indistinguishable among groups. Forty nondiabetic peripubertal boys served as controls. Similar to those in the normal boys, circulating GH concentrations and serum IGF-I levels increased during puberty in the boys with IDDM. The augmented circulating GH concentrations occur due to an increase in GH secretion, as determined by calculated daily GH production rates (760 +/- 119 vs. 1025 +/- 121 vs. 1821 +/- 266 micrograms/day, respectively for the 3 groups). IGF-I levels were decreased in prepuberty in the boys with IDDM and were overcome with increasing pubertal development (0.68 +/- 0.13 vs. 0.78 +/- 0.11 vs. 1.53 +/- 0.20 U/mL; P < 0.05). There was an increase in the maximal rate of GH secretion per burst (amplitude) during prepuberty (0.54 +/- 0.05 vs. 0.88 +/- 0.17 microgram/L.min, control vs. IDDM; P = 0.03) and early puberty (0.64 +/- 0.10 vs. 0.88 +/- 0.10 microgram/L.min; p = 0.04). The differences in amplitude between the controls and the boys with IDDM were absent once puberty was well established (1.00 +/- 0.10 vs. 1.02 +/- 0.14 microgram/L.min; P > 0.05). The metabolic clearance of GH was increased in the late pubertal boys with IDDM compared to that in their controls (GH half-life, 24.0 +/- 1.0 in control vs. 19.8 +/- 0.5 min in diabetics; P = 0.006). We conclude that comparable increments in GH secretion and serum IGF-I levels in boys with IDDM in moderate glycemic control and controls are presumably related to increased levels of testosterone in both groups. However, differences exist with respect to GH secretory burst amplitude (augmented) and serum IGF-I concentrations (decreased) before puberty is reached. These alterations disappear with the establishment of puberty.
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PMID:Alterations in growth hormone secretion and clearance in adolescent boys with insulin-dependent diabetes mellitus. 837 Jun 85

Membrane-associated tyrosine phosphatase activities were studied in two distinct states of insulin resistance: diabetes and pregnancy. Using a novel immunoenzymatic assay with intact insulin-like growth factor-I (IGF-I) and insulin receptors as substrates, we show that phosphotyrosine-protein phosphatases (PTP-ases) from normal rat tissues induce a decrease in tyrosine phosphorylation of both receptors. Membrane fractions from kidney, brain, and liver contain the highest PTP-ase activity toward the insulin receptor. After 20-day streptozotocin-induced diabetes, PTP-ase activities are increased by 70% in the placenta, reduced by 40-50% in liver and skeletal muscle, and remained unchanged in the nonclassical insulin target tissues, kidney and brain. In general, the dephosphorylation of IGF-I receptor follows a pattern similar to that of insulin receptor except in red skeletal muscle in which it is not modified. Pregnancy also induces alterations of liver PTP-ases similar to those elicited by diabetes with a 50% reduction of insulin and IGF-I receptor dephosphorylation. This effect of pregnancy is further potentiated by diabetes. The alterations in the activity of hepatic PTP-ases from diabetic and pregnant rats are associated with a decreased autophosphorylation of the insulin receptor, suggesting that the diminution of phosphatase activity might be associated to the state of receptor phosphorylation and activation. Our data demonstrate that alterations of PTP-ases in insulin target tissues are found in two insulin-resistant states, one characterized by hyperinsulinemia, pregnancy and one by insulinopenia, streptozotocin-diabetes. These observations suggest a possible relationship between the defective activity of receptor tyrosine kinases and membrane-associated phosphatases from insulin responsive tissues.
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PMID:Alteration of phosphotyrosine phosphatase activity in tissues from diabetic and pregnant rats. 841 48

Linear growth retardation is common in uncontrolled insulin-deficient diabetes, but individual organs such as kidney may hypertrophy. To explore whether this heterogeneity of response might be mediated by differential local insulin-like growth factor-I (IGF-I) gene regulation, we injected rats with ip saline, 65, 120, or 175 mg/kg streptozotocin (STZ). Diabetics were untreated or received daily insulin. Animals were killed 24, 48, or 72 h after documentation of diabetes, and liver, kidney, and lung messenger RNA (mRNA) content analyzed by solution hybridization/RNase protection assay. Untreated diabetics had 10- to 100-fold reductions in hepatic IGF-I mRNA apparent as early as 24 h, and the magnitude of these changes varied directly with the severity of diabetes. In contrast, kidney IGF-I mRNA content increased by 400-500% at 24 h in untreated diabetics given 175 mg/kg STZ, and by 100-200% at 48 h in those given 120 mg/kg STZ, with return to control levels by 72 h. Renal IGF-I mRNA levels actually decreased by 250-350% at 24 h in rats injected with 65 mg/kg STZ, returning to supranormal values by 72 h. These results suggest that severity and/or duration of the metabolic abnormality qualitatively and quantitatively affect this response in the kidney. Liver and kidney IGF-I mRNA levels approached normal with insulin therapy and were similar to controls in rats which received STZ but did not develop diabetes. Lung IGF-I mRNA levels were minimally altered in all experimental groups. At the time point and STZ dosage at which liver IGF-I mRNA changes were most dramatic, little change in liver alpha-tubulin mRNA was noted. At the time point and STZ dosages at which kidney IGF-I mRNA induction was most dramatic, renal IGF-I receptor mRNA was only minimally changed, and renal alpha-tubulin mRNA was modestly reduced. In summary: 1) hepatic IGF-I mRNAs are dramatically reduced, and renal IGF-I mRNAs are significantly increased soon after the onset of insulin-deficient diabetes in STZ-treated rats; 2) insulin therapy restores IGF-I mRNA levels toward normal; and 3) these changes in IGF-I mRNA content are specific and are not the result of hepatic or renal STZ toxicity. These data suggest that IGF-I gene expression is regulated in a discordant, organ-specific manner in diabetes, and that metabolic factors in addition to GH may differentially modulate the endocrine and paracrine effects of IGF-I on growth.
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PMID:Discordant, organ-specific regulation of insulin-like growth factor-I messenger ribonucleic acid in insulin-deficient diabetes in rats. 842 71

As previously reported, activation of the adrenocorticotropic hormone (ACTH)-adrenal cortical axis in rats with insulin-dependent diabetes mellitus (IDDM) reduces their growth and circulating insulin-like growth factor-I (IGF-I) levels and induces a resistance to growth hormone (GH) and IGF-I. The studies reported herein were conducted to determine whether the pituitary and/or adrenal gland influence the changes in basal and GH-stimulated serum concentrations of IGF-binding proteins (IGFBPs) in rats with IDDM. Male rats were made diabetic by injections of streptozotocin. Intact nondiabetic (NonDb), diabetic (Db), hypophysectomized diabetic (HxDb), and adrenalectomized diabetic (AxDb) rats were injected twice daily with 50 micrograms porcine (p) GH or with 0.9% saline for 2 weeks following the surgeries. Changes in serum IGFBP concentrations were determined by Western ligand- or immuno-blot analysis. Neither IGFBP-5 nor -6 was detected in any of the treatment groups. Induction of IDDM increased serum concentrations of IGFBP-1 and -2 and reduced those of IGFBP-3 and -4. Although serum IGFBP-1 and -2 concentrations remained elevated in the HxDb rats compared with the NonDb controls, IGFBP-1 levels were reduced compared with those in the Db controls. Serum IGFBP-3 and -4 were reduced to levels below those in Db controls. Although IGFBP-3 and -4 concentrations were elevated to normal in AxDb rats, the IGFBP-2 concentration was increased above those in both NonDb and Db rats and the IGFBP-1 concentration was reduced. Administration of pGH increased serum IGFBP-4 concentrations in all groups and IGFBP-3 concentrations in all groups except the Db. In addition, pGH reduced the concentration of IGFBP-1 in HxDb rats and nearly abolished it in AxDb rats, but had no effect on IGFBP-1 concentration in NonDb or Db rats. Administration of corticosterone (B; 25 micrograms/ml of 0.9% saline drinking water) to AxDb rats restored Db-like profiles of all IGFBPs. The refractoriness of Db rats to pGH is associated with a failure of the hormone to elevate IGFBP-2 and -3 titers and to reduce those of IGFBP-1. Adrenal B production appears to be responsible for this resistance to GH. However, the elevated IGFBP-2 concentration in Db rats does not appear to be due to B or any other pituitary-controlled or -derived factors. Impaired growth was associated with substantially reduced IGFBP-3 concentrations and elevated IGFBP-1, whereas growth restoration was associated with the opposite changes.
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PMID:Regulation of insulin-like growth factor-binding proteins in rats with insulin-dependent diabetes mellitus. 853 61


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