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

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

Growth hormone secretion is markedly suppressed early in streptozocin induced diabetes mellitus of the rat. Our studies were designed to delineate early changes in hypothalamic regulation by growth hormone-releasing hormone (GHRH) and somatostatin (SS) with the aim of determining the best time period for hypothalamic secretion studies. Although hypothalamic GHRH content (ng/hypothalamus) and SS concentration (ng/mg wet weight) were unchanged at 17 to 20 days in previous studies, we anticipated changes earlier in the time course from transient imbalances in release and synthesis. We examined hypothalamic GHRH content and SS concentration in control, diabetic, and insulin treated diabetic rats (n = 5-13; streptozocin 100 mg/kg i.p.) at 0, 2, 4, 7, 10 and 21 days. In diabetic rats GHRH content was greater at day 2 (142 +/- 9% of control-same day, P < 0.05) and day 4 (139 +/- 17%, P < 0.05), but was less at day 10 (67 +/- 4%, P < 0.01). GHRH content of insulin treated diabetic rats was elevated at day 2 (158 +/- 10%, P < 0.05), but subsequently was unchanged from control. In diabetic rats SS concentration was decreased at day 4 (78 +/- 5%, P < 0.01) and at day 21 (91 +/- 3%, P < 0.05). Our results show earliest changes compared to control in GHRH content at 2 days and in SS concentration at 4 days. These findings support early changes in hypothalamic secretion, define a time period of 1 to 10 days for further studies of release and gene expression, and suggest complex relationships of gene expression, peptide synthesis, and peptide release.
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PMID:Time course of hypothalamic growth hormone-releasing hormone and somatostatin content in streptozocin diabetic rats: evidence for early changes in hypothalamic regulation. 755 96

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

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

Growth hormone (GH) hypersecretion has been described in diabetes mellitus and seems to be involved in the pathogenesis of diabetes complications. As pirenzepine (PZ), a cholinergic muscarinic antagonist, is able to inhibit GH hypersecretion in insulin-dependent diabetes mellitus (IDDM), we investigated whether PZ is also able to inhibit spontaneous and stimulated GH-release in non-insulin-dependent diabetes mellitus (NIDDM). Ten non-obese well-controlled patients with NIDDM underwent in random order the following three double-blind one week treatments: placebo (PL), PZ at low dose (PL in the morning plus PZ 50 mg at 22 h) or high dose (PZ 50 mg at 8 h plus 100 mg at 22 h). Pirenzepine administration significantly (p < 0.05) decreased nocturnal GH release after both low and high dose (AUC, PL vs PZ: 107.3 +/- 26.5 vs 48.3 +/- 10.5 and 57.6 +/- 9.6 micrograms/L/h, respectively). The GH response to arginine infusion was significantly inhibited by PZ at high dose (AUC, 147.1 +/- 48.8 vs 444.7 +/- 194.3 micrograms/L/h, p < 0.01), but not at low dose. Glucose, insulin, glucagon and somatostatin responses to arginine infusion were not changed by pirenzepine treatment. In conclusion, the muscarinic blockade by PZ is able to inhibit the spontaneous and stimulated GH secretion also in NIDDM without affecting insulin secretion.
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PMID:Pirenzepine decreases basal and stimulated GH secretion in patients with type 2 (non-insulin-dependent) diabetes mellitus. 800 63

Insulin stimulates glucose uptake and non-oxidative glucose metabolism (predominantly glycogen synthesis) in skeletal muscle. Among other things, insulin resistance is characterized by a subnormal insulin-stimulated glucose disposal, and it appears to be associated with an increased risk for development of non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present investigation has been to elucidate the mechanism of action of insulin on non-oxidative glucose metabolism both during conditions of insulin resistance and during physiological modification of glucose metabolism. To do so, the effect of insulin was investigated both with respect to its initial activation of the insulin receptor kinase and the terminal step of the signal pathway, namely stimulation of the glycogen synthase. From needle biopsies of human skeletal muscle (vastus lateralis) cellular membranes were solubilized and the insulin receptors were partially purified by affinity chromatography using wheat germ agglutinin. Subsequently insulin binding and the insulin-stimulated tyrosine kinase activity were characterized. The insulin receptor kinase activity did not change during physiological modification of the glucose metabolism (exercise training, acute exercise, growth hormone exposure or experimental hyperglycemia). No specific abnormalities of the insulin receptor kinase activity were revealed in insulin-dependent diabetes (IDDM) or in common NIDDM. In addition, insulin receptor kinase activity did not change during dietary or sulphonylurea treatment of NIDDM. Glucose deposition as glycogen in muscle is regulated by glycogen synthase (GS), which during insulin stimulation undergoes dephosphorylation and becomes more active at physiological concentrations of glucose-6-phosphate. Recently, insulin was shown to stimulate a cascade of phosphorylation-dependent kinases which ultimately activate a glycogen-bound subunit of a phosphatase (G-subunit of phosphatase-1) which promotes dephosphorylation GS by the catalytic subunit. The quantity of the GS enzyme (GStot) in muscle may be reduced in the diabetes disease. However, it may increase during physical training of insulin-dependent diabetic patients. GStot is not altered during acute exposure to insulin, hyperglycemia or muscle contraction. The insulin stimulation of GS is reduced in insulin resistant NIDDM patients. However, once the hyperglycemia and the insulin resistance is ameliorated during treatment with diet or sulphonylurea drugs the activation of GS improves. Growth hormone-induced transient insulin resistance in non-diabetic subjects, is accompanied by a reduced insulin stimulation of GS. Experimentally induced hyperglycemia in normal subjects has no influence on GS activation by insulin. After an acute exercise bout the GS in muscle becomes activated. The mechanism of this post-exercise GS activation is still unknown.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Insulin receptor function and glycogen synthase activity in human skeletal muscle. Physiology and pathophysiology. 803 33

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

In order to determine whether acromegaly is still associated with increased mortality, a hospital case note review of all patients with acromegaly followed up in Stoke-on-Trent since 1967 was carried out. Of 79 subjects identified, 51 are alive and being monitored and 28 have died. Mortality was compared to the general population by life table analysis. Secretion of growth hormone was assessed and compared in dead and alive patients. The effect of diabetes, hypertension, and growth hormone secretion on long-term outcome was assessed. Acromegaly is still associated with increased mortality, with an overall ratio of observed to expected deaths equal to 2.68 (95% C.I. 1.8-3.9; p < 0.001), but the survival of 31 (39%) patients whose growth hormone level had been reduced to below 5 mU/l was equal to that of the general population (O/E = 1.42; 95% C.I. 0.46-3.31: p > 0.05). The dead patients had had significantly higher growth hormone levels than those still alive, but mortality did not appear to be influenced by diabetes or hypertension. The cause of death was vascular in 57% of cases. Growth hormone hypersecretion is still associated with excess mortality in acromegaly. The present study suggests that the therapeutic objective should be to lower average daytime growth hormone levels to less than 5 mU/l. There is need for a large study to compare different modes of treatment in terms of their effect on growth hormone secretion and on long-term outcome.
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PMID:An audit of outcome of treatment in acromegaly. 832 47

Growth hormone (GH), insulin-like growth factor-1 (IGF-1) and prolactin (PRL) in blood and urine were observed in 20 patients with acromegaly in a double-blind placebo-controlled 14-day clinical trial with the somatostatin analog octreotide. Hormones were determined by the same radioimmunoassays in blood and urine. Significant reduction of GH and IGF-1 during octreotide treatment compared to placebo was seen in blood but not in urine. Patients with diabetes mellitus, 2 of the 20 patients, showed notably increased urinary GH and IGF-1 in relation to blood levels. Therefore, results without the two diabetic patients were calculated, showing significant reduction of urinary GH and IGF-I during treatment on some, but not all observation days. The intraindividual variations of GH and IGF-1 were greater in urine than in blood. PRL levels were not significantly affected by octreotide either with or without the two diabetic patients. In conclusion, this study indicates, that GH and IGF-1 in blood are preferable to urinary GH and IGF-1 as response markers during treatment of acromegaly with octreotide. One disadvantage with urinary assessments of GH and IGF-1 in acromegaly seems to be the relatively higher excretion in patients with diabetes mellitus.
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PMID:Growth hormone and insulin-like growth factor-1 in blood and urine as response markers during treatment of acromegaly with octreotide: a double-blind placebo-controlled study. 851 80

The present study focuses on the pathogenesis of increased frequency of large-vessel disease in diabetes. The diabetic arterial wall displays characteristic alterations of the extracellular matrix secreted by arterial smooth-muscle cells. The effects of insulin and growth hormone on the synthesis of sulphate-labelled proteoglycans and heparan sulphate proteoglycan were studied. Proteoglycans and heparan sulphate proteoglycan were obtained from the medium and the cell layer of cultured human arterial smooth-muscle cells grown in 5% human serum. Heparan sulphate proteoglycan was quantified using ethanol precipitation combined with specific enzyme degradation. Addition of insulin (0.01, 0.05 and 0.10 mU/ml) induced a significant accumulation of 35S-labelled proteoglycans in the cell layer (2p < 0.005 and 2p < 0.001). The relative amount of cell-associated heparan sulphate proteoglycan increased during insulin stimulation (2p < 0.05). Growth hormone stimulation (5.0 and 10.0 ng/ml) caused a significant decrease in the ratio between heparan sulphate proteoglycan and proteoglycan in the cell layer (2p < 0.02 and 2p < 0.01), whereas the distribution of proteoglycans between the cell layer and the medium was unaltered.
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PMID:Effect of insulin and growth hormone on the synthesis of radiolabelled proteoglycans from cultured human arterial smooth-muscle cells. 861 30


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