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)

Acute streptozotocin (STZ)-induced diabetes in rats causes a transient increase in insulin-like growth factor-I (IGF-I) in the kidney, followed by a rapid renal hypertrophy and constant renal hyperperfusion. However, renal IGF-I levels return to normal within 4 days. Thus, hyperperfusion, which is independent of renal hypertrophy of the chronically diabetic kidney, is not explained by increased renal IGF-I. We studied IGF-I and IGF-I receptor gene expression in the kidney of rats with long-standing STZ-induced diabetes. IGF-I mRNA level in the chronically diabetic kidney was approximately 50% of that in control rats, whereas IGF-I receptor mRNA was increased approximately threefold. Ten days' treatment with insulin 65 days after induction of diabetes resulted in a glucose-dependent decrease in IGF-I receptor mRNA. Chronic hyperinsulinemia with near normoglycemia did not change gene expression of either IGF-I or IGF-I receptor. The studies suggest that glucose levels per se, independent of insulin levels, play an important role in the regulation of IGF-I receptor gene expression in the chronically diabetic kidney. Furthermore, kidney hyperperfusion in chronic diabetes is coupled with the increase in IGF-I receptor mRNA, despite normal kidney IGF-I levels.
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PMID:Insulin-like growth factor-I (IGF-I) and IGF-I receptor gene expression in the kidney of the chronically hypoinsulinemic rat and hyperinsulinemic rat. 754 52

Insulin-like growth factor-I (IGF-I) gene transcription is mediated largely via exon 1. In an initial search for regulatory regions, rat hepatocytes were transfected with IGF-I constructs. Since omission of downstream sequences led to reduced expression, we then used in vitro transcription to evaluate potential metabolic regulation via downstream regions. With templates including 219 base pairs of downstream sequence, transcriptional activity was reduced 70-90% with hepatic nuclear extracts from diabetic versus normal rats. However, activity was comparable with templates lacking downstream sequences. The downstream region contained six DNase I footprints, and templates with deletion of either region III or V no longer provided reduced transcriptional activity with nuclear extracts from diabetic rats. Nuclear protein binding to regions III and V appeared to be metabolically regulated, as shown by reduced DNase I protection and activity in gel mobility shift assays with nuclear extracts from diabetic rats. Southwestern blotting probes corresponding to regions III and V recognized a approximately 65-kDa nuclear factor present at reduced levels in diabetic rats. These findings indicate that a downstream region in exon 1 may be important for both IGF-I expression and metabolic regulation. Altered concentration or activity of a transcription factor(s) binding to this region may contribute to reduced IGF-I gene transcription associated with diabetes mellitus.
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PMID:Transcriptional regulation of the rat insulin-like growth factor-I gene involves metabolism-dependent binding of nuclear proteins to a downstream region. 755 17

In rats and men the sulfonylurea glibenclamide augmented skeletal growth. However, with the design of the in vivo studies it was not possible to distinguish whether the growth promoting effect of glibenclamide was mediated by the augmented peripheral insulin or IGF-I levels or if the sulfonylurea had a direct effect on chondrocytes. We therefore measured clonal growth of isolated human chondrocytes in response to glibenclamide in vitro. Cells were isolated from human nose septal cartilage and incubated in a semi-solid medium. Colony formation in response to glibenclamide and IGF-I was determined. Glibenclamide stimulated clonal growth of chondrocytes in a bell-shaped fashion (p < 0.001). 50 ng/ml glibenclamide as the maximal dose augmented colony formation to 144 +/- 9% compared to clonal growth without glibenclamide in the incubation medium, which was designated as 100%. Basal values were obtained with 200 ng/ml glibenclamide. Insulin-like growth factor-I (IGF-I) at 3 ng/ml (118 +/- 4%) and 25 ng/ml (149 +/- 8%, p < 0.02) stimulated growth of chondrocytes. To elucidate the possible mechanism of glibenclamide on clonal growth, chondrocytes were incubated with the sulfonylurea and the IGF-I receptor antibody alpha IR-3. The antibody completely abolished the effect of glibenclamide on colony formation. The results suggest that the growth promoting effect of glibenclamide on isolated human chondrocytes is mediated by IGF-I dependent mechanisms.
Exp Clin Endocrinol Diabetes 1995
PMID:Glibenclamide stimulates growth of human chondrocytes by IGF I dependent mechanisms. 758 33

To address the relationship of insulin-like growth factor-I (IGF-I) to diabetes control, we determined IGF-I levels in 137 subjects age 17 yr and younger with recently diagnosed insulin-dependent diabetes mellitus in a population-based cohort study between 3 and 11 months after diagnosis (mean 4.9 months). Initial determinations of IGF-I, 24-h urine C-peptide and microalbuminuria, age, sex, height, weight, body mass index, pubertal stage, and glycosylated hemoglobin (GHb) were obtained. IGF-I levels ranged from 11-439 ng/mL, were strongly related to age (r = 0.74, P < 0.001), and were higher in females than males at any given age (P < 0.01). IGF-I was inversely related to GHb (partial r = -0.43, P < 0.001) after adjustment for sex and age. The relationship between IGF-I and GHb did not change between age groups (< 6, 6-9, > or = 10 yr of age; P = 0.50), and it did not change between prepubertal and pubertal subjects (P = 0.95). IGF-I was not related to 24-h urine C-peptide or microalbuminuria. These results suggest that lower IGF-I levels are related to poorer metabolic control of diabetes in the period following insulin-dependent diabetes mellitus diagnosis in all young persons regardless of age or pubertal status.
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PMID:Insulin-like growth factor-I is related to glycemic control in children and adolescents with newly diagnosed insulin-dependent diabetes. 760 67

Growth hormone (GH) plays an important role in glucose homeostasis in both healthy subjects and patients with diabetes. Patients with poorly controlled insulin-dependent diabetes mellitus (IDDM) have high basal and integrated serum GH concentrations, as well as an enhanced GH response to several secretagogues. Yet, these patients have impaired generation of insulin-like growth factor-I (IGF-I). These abnormalities tend to return to normal as an adequate metabolic control is achieved. In view of this hormonal profile, IDDM has been considered a state of relative GH resistance. Studies in experimental animals with streptozotocin-induced diabetes have shown a decreased binding of radiolabeled GH to liver membranes. More recently, adults and children with IDDM have been found to have low levels of the high affinity growth hormone binding protein (GHBP), which represents the extracellular portion of the GH receptor, and is thought to reflect GH receptor tissue concentrations. The abnormalities in the GH/IGF-I axis have been implicated in the worsening of metabolic control that occurs in some patients, as well as in the development of microvascular complications, particularly retinopathy.
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PMID:Characteristics of the somatotropic axis in insulin dependent diabetes mellitus. 762 Feb 73

The underlying etiology of diabetic microvascular disease remains unknown. To examine the potential contribution of basic fibroblast growth factor (bFGF), which is an angiogenic factor, and insulin-like growth factor-I (IGF-I) to the development of diabetic microvascular disease, bFGF and IGF-I mRNA levels were measured in tissues of control, diabetic, and insulin-treated diabetic rats. Diabetes was induced in rats by intravenous injection of streptozotocin (STZ) 65 mg/kg, and the rats were maintained for 21 days. bFGF mRNA levels increased threefold in the eyes of diabetic versus control rats, whereas a consistent change in bFGF mRNA levels was not observed in other tissues. In contrast, IGF-I mRNA levels decreased in the eyes and other tissues, including kidney, lung, and skeletal muscle, of diabetic as compared with control rats. Insulin treatment prevented the diabetes-induced increase in bFGF and decrease in IGF-I mRNA levels. Acidic FGF (aFGF) mRNA levels were unchanged in eyes from diabetic versus control rats. In partially purified retinas, diabetes increased bFGF mRNA levels twofold as compared with levels in control retinas, whereas IGF-I mRNA levels decreased to 58% of control levels in retinas from diabetic rats. Insulin treatment again prevented the diabetes-induced increase in IGF-I mRNA levels in the retina but had no effect on the diabetes-induced increase in bFGF mRNA levels. bFGF peptide levels were minimally increased in diabetic versus control retinas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of growth factor mRNA levels in the eyes of diabetic rats. 763 45

Experimental evidence has suggested that insulin-like growth factor-I (IGF-I) may contribute to diabetic complications. Previously, we and others have shown that normal glomerular mesangial cells have receptors for, synthesize, and exhibit a mitogenic response to IGF-I. We investigated the IGF-I response in cells derived from a genetic model of diabetes, the nonobese diabetic (NOD) mouse. Mesangial cell lines were derived from diabetic (D-NOD) and nondiabetic adult mice. D-NOD cells released more IGF-I into the supernatant and had a decreased binding of IGF-I to surface receptors. Analysis according to Scatchard revealed a decreased number of receptor sites on D-NOD cells, although the structure of the IGF-I receptor visualized by cross-linking was identical for both cell types. Preincubation of D-NOD cells with an antibody to IGF-I resulted in an increase in the number of receptor sites. This suggested that autocrine IGF-I was responsible for the decrease in D-NOD receptor number and that diabetes had resulted in a stable phenotypic change.
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PMID:Mesangial cells from diabetic NOD mice constitutively secrete increased amounts of insulin-like growth factor-I. 769 81

Effect of insulin-like growth factor-I (IGF-I) on protein metabolism was investigated in burned rats receiving TPN. Twenty-six male SD rats were divided into two groups. IGF-I was administered to group IGF (IGF-I group, n = 14), but not to group C (Control group, n = 12). Loss of body weight after burn in group IGF was significantly lower than group C (p < 0.01). Cumulative nitrogen balance for 2 postburn days in group IGF was significantly higher than group C (p < 0.01). Rate of whole body protein turnover, synthesis and breakdown increased significantly in group IGF compared with group C. On the other hand, blood glucose was decreased significantly in group IGF (p < 0.05). Water balance made no significant difference between two groups. In group IGF, weight of the spleen, kidney, small intestine and colon increased significantly. Fractional synthesis rate and protein content of mucosa of the small intestine were significantly higher in group IGF than group C. From the histological point of view, mucosal layer was thickened and hyperplastic. Catabolism and surgical diabetes are caused in the surgical stress, and the administration of IGF-I are thought to be effective for improvement of those conditions. And IGF-I has the most remarkable effect on the small intestine of all organs studied in our experiment.
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PMID:[Effects of insulin-like growth factor-I in burned rats]. 770 46

Previous reports concerning insulin-like growth factor-I (IGF-I) in diabetics are conflicting. This study describes IGF-I in children with insulin-dependent diabetes mellitus (IDDM) and healthy controls in relation to pubertal development. Sixty-six children participated (34 girls and 32 boys) of which 33 had IDDM. The mean age in the study population was 14.3 years, (range 7.1 to 19.7). Serum IGF-I was significantly decreased in diabetics. Diabetic girls had a mean IGF-I of 28.3 (14.4; = SD) nmol/l compared with 42.8 (15.0) nmol/l in controls. In diabetic boys the result was 30.0 (16.0) nmol/l compared with 44.1 (23.4) in controls. Growth hormone was measured in only one fasting morning serum sample from each individual. There was no difference between girls, but diabetic boys had higher mean serum concentration of growth hormone than controls (3.5 (4.8) vs. 1.8 (1.5) micrograms/l respectively). Diabetic girls had delayed menarche, corresponding to a slightly delayed bone maturation.
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PMID:Decreased serum insulin-like growth factor I during puberty in children with insulin dependent diabetes mellitus (IDDM). 771 26

The salivary glands of mammals synthesize and secrete a number of peptide growth factors that play important roles in cell/tissue homeostasis and embryonic development. Using a radioimmunoassay, insulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) were detected in saliva from mice. Unlike epidermal growth factor (EGF), there was no sexual dimorphism in the concentrations of the insulin growth factor family. Immunohistochemical localization of IGF-I and IGF-II was confined to the duct cells of both the parotid and the submandibular glands. Reverse transcriptase-polymerase chain reaction amplification of total RNA from parotid and submandibular glands confirmed the presence of all three hormone/growth factor mRNAs in both glands. The levels of insulin and IGF-I were higher in saliva from an animal model for autoimmune type 1 diabetes, the non-obese diabetic (NOD) mouse, than in a second inbred strain, BALB/c. In contrast, the IGF-II levels were decreased relative to the BALB/c strain. With the onset of diabetes in NOD mice, insulin levels declined, while IGF-I and IGF-II levels showed trends toward lower levels of these growth factors when compared with non-diabetic animals. These changes were reflected in the concentrations from parotid and submandibular gland cell lysates.
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PMID:Detection of insulin and insulin-like growth factors I and II in saliva and potential synthesis in the salivary glands of mice. Effects of type 1 diabetes mellitus. 776 95


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