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

Insulin-like growth factor I (IGF-I) is a useful therapeutic agent in insulin resistant diabetes mellitus due to insulin receptor disease because of its hypoglycaemic effects through the IGF-I receptor. A girl with typical type A insulin resistant syndrome was treated with IGF-I for two years and the treatment was effective in ameliorating hyperglycaemia. Overproduction of testosterone in polycystic ovaries was aggravated with this treatment, however. Therefore, IGF-I treatment may be used for glycaemic control but with caution because of its possible side effect of aggravating hyperandrogenism in these patients.
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PMID:Long-term follow up in type A insulin resistant syndrome treated by insulin-like growth factor I. 794 36

In vivo resistance to the action of insulin on glucose uptake has been documented during puberty. To test the hypothesis that the glucose-fatty acid cycle, as proposed by Randle et al. (Randle PJ, Garland PB, Hales CN, Newsholme EA: The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785-789, 1963), may be responsible for this phenomenon, we studied nine prepubertal (Tanner I), nine pubertal (Tanner II-IV), and five young adult healthy subjects. The rate of lipolysis was measured with [d-5]glycerol tracer during basal state and during a stepwise hyperinsulinemic (10 and 40 mU.m-2.min-1)-euglycemic clamp. The rates of insulin-stimulated glucose disposal (Rd) were measured during the clamp, whereas glucose and fat oxidation were measured by using indirect respiratory calorimetry. Basal glycerol rate of appearance (Ra; lipolysis) and fat oxidation were similar between prepubertal and pubertal subjects but higher than adults when the data were expressed per kilogram body weight or per kilogram fat-free mass (FFM; glycerol Ra: 2.5 +/- 0.2, 2.6 +/- 0.2 vs. 1.6 +/- 0.2 mumol.min-1.kg FFM-1, P < 0.05; fat oxidation: 4.4 +/- 0.6, 4.8 +/- 0.3 vs. 3.2 +/- 0.6 mumol.min-1.kg FFM-1, P < 0.05). However, when expressed for total body, glycerol Ra and fat oxidation were higher in pubertal versus prepubertal and adult subjects. Insulin-like growth factor I (IGF-I) levels correlated with total-body lipolysis (r = 0.52, P = 0.006) and with total lipid oxidation (r = 0.44, P = 0.016) at baseline.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1994 Jul
PMID:Correlations between fatty acid and glucose metabolism. Potential explanation of insulin resistance of puberty. 801 56

Insulin-like growth factor I (IGF-I) has acute insulin-like metabolic effects and long-term anabolic actions. The therapeutic potential of recombinant human IGF-I treatment is being investigated in various growth hormone-resistant and insulin-resistant disorders. Recent studies have shown that IGF-I may substitute for growth hormone in promoting linear growth in children with growth hormone insensitivity. The anabolic, protein-sparing action of IGF-I is being evaluated as a potential therapy for adults with catabolic diseases. Patients with insulin-dependent diabetes mellitus have reduced endogenous IGF-I production, and studies are in progress to determine whether treatment with IGF-I in addition to insulin may improve their metabolic/anabolic status. Insulin-like growth factor I treatment may reduce glucose and triglyceride levels in adults with non-insulin-dependent diabetes mellitus and in some patients with extreme insulin resistance. Further studies are needed to evaluate the efficacy and safety of IGF-I treatment in these and other conditions and to provide a better understanding of this hormone's normal physiologic role(s) and complex relations with growth hormone and insulin.
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PMID:Clinical uses of insulin-like growth factor I. 806 60

Homogeneous cultures of calf glomerular mesangial and endothelial cells were found to be active in the synthesis of type VI as well as type IV collagen in contrast to the epithelial cells that were devoted primarily to the production of the latter collagen. Studies with rat mesangial cells indicated that they responded to high glucose (20 mM) in the medium by a significant (P < 0.001) increase in type VI collagen synthesis as measured by the production of the protein and its mRNA level, both of which were closely correlated to each other and to glucose consumption. Similar observations were made with type IV collagen, but the enhanced formation of this protein was not as rapidly apparent as that of type VI and, moreover, could not be as readily reversed on restoration of the glucose to a physiological level (5 mM). Evaluation of a number of other agents indicated that although mannitol had no effect, L-glucose and NaCl significantly stimulated synthesis of both type VI and IV collagens and glucose consumption. Insulin-like growth factor I and aldosterone, on the other hand, also increased glucose consumption but brought about an enhancement of only type IV collagen production, suggesting that the two collagens are independently regulated. This possibility was supported by our observation that pyruvate, which was actively taken up by the cells, selectively stimulated type IV collagen production.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1994 Jan
PMID:Synthesis of type VI collagen by cultured glomerular cells and comparison of its regulation by glucose and other factors with that of type IV collagen. 826 24

The complications of diabetes arise in part from abnormally high cellular glucose uptake and metabolism. To determine whether altered glucose transporter expression may be involved in the pathogenesis of diabetic nephropathy, we investigated the effects of elevated extracellular glucose concentrations on facilitative glucose transporter (GLUT) expression in rat mesangial cells. GLUT1 was the only transporter isoform detected. Cells exposed to 20 mmol/l glucose medium for 3 days demonstrated increases in GLUT1 mRNA (134%, P < 0.002), GLUT1 protein (68%, P < 0.02), and V(max) (50%, P < 0.05) for uptake of the glucose analog [3H]2-deoxyglucose (3H2-DOG), when compared to cells chronically adapted to physiologic glucose concentrations (8 mmol/l). The increase in GLUT1 protein was sustained at 3 months, the latest time point tested (77% above control, P < 0.01). In contrast, hypertonic mannitol had no effect on GLUT1 protein levels. Insulin-like growth factor I (IGF-I; 30 ng/ml) increased the uptake of 3H2-DOG by 28% in 8 mmol/l glucose-treated cells (P < 0.05) and by 75% in cells switched to 20 mmol/l glucose for 3 days (P < 0.005). These increases in 3H2-DOG uptake occurred despite a lack of effect of IGF-I on GLUT1 protein levels (P > 0.5 vs. control). Therefore, hyperglycemia and IGF-I treatment both lead to increases in mesangial cell glucose uptake, and hyperglycemia induces increased GLUT1 expression, which can directly lead to the pathological changes of diabetic nephropathy. The effects of high glucose and of IGF-I to stimulate 3H2-DOG uptake also appear to be additive.
Diabetes 1997 Jun
PMID:D-glucose stimulates mesangial cell GLUT1 expression and basal and IGF-I-sensitive glucose uptake in rat mesangial cells: implications for diabetic nephropathy. 916 76

Insulin-like growth factor I (IGF-I) is vasodilatory and mitogenic for vascular smooth muscle cells (VSMC). Alteration in VSMC Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity is hypothesized to underlie abnormal vascular tone and growth in hypertension and diabetes. Therefore, we investigated effects of IGF-I on Na(+)-K(+)-ATPase activity in rat aortic VSMC. IGF-I increases pump activity in a dose- and time-dependent manner: the minimal dose required was 10(-10) M, and the minimal time required was 20 min (at 10(-8) M) to increase activity. Similar effects persisted through 12 h. In Na(+)-loaded cells, IGF-I does not further stimulate activity. Blockade of Na+/H+ exchange attenuates IGF-I-induced increases in activity after 30 min but has no effect after 12 h. Northern blot analyses reveal that expression of the alpha 1- and the alpha 2-subunits of the pump were unaffected by IGF-I. Plasma membrane alpha 1- and alpha 2-protein were also unaffected, suggesting translocation of preformed pools was not responsible for the increases. Inhibitors revealed that neither tyrosine kinase activity, RNA transcription, protein synthesis, nitric oxide synthase activity, or protein kinase C activity mediated this IGF-I effect. Therefore, IGF-I regulates Na pump activity in the short term by an Na+/H+ exchange-dependent but transcription/translocation-independent mechanism. These data suggest that IGF-I, known to be produced by VSMC, may regulate tone and growth responses abnormal in disease states such as hypertension and diabetes.
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PMID:IGF-I regulation of Na(+)-K(+)-ATPase in rat arterial smooth muscle. 925 87

Chronic hyperglycemia may cause growth factor alterations that are likely to participate in tissue remodeling typical for diabetic late complications. However, few details of such events are known. The ocular vitreous fluid allows studies of growth factor levels in human eyes (after vitrectomy). The vitreous is highly inert and protected by the blood-retina barrier and thus probably reflects growth factor production by the normal retina. Vitreous from patients with proliferative diabetic retinopathy (PDR) was compared with vitreous obtained from patients with nonproliferative eye disease and with vitreous from patients without diabetes but with marked neovascular proliferations due to ischemia. This design permits us to distinguish diabetes-related from non-diabetes-related alterations. Insulin-like growth factor I (IGF-I), IGF-II, IGF binding protein 2 (IGFBP-2), and IGFBP-3 were elevated 3- to 13-fold in nondiabetic retinal ischemia and 1.5- to 3-fold in PDR, indicating that the changes were not restricted to diabetes. These changes may partially be explained by leakage of serum into the vitreous, since IGFs and IGFBPs are 20- to 50-fold higher in serum than in vitreous, and vitreous protein content was 1.5-fold elevated in PDR subjects and 5-fold in ischemia patients compared with control subjects. TGF-beta is a proposed antiangiogenic factor in the eye. TGF-beta2 was the predominant subtype in vitreous, and its total amount was not altered in PDR patients. More importantly, the active fraction of TGF-beta was decreased by 30 and 70% in PDR and nondiabetic retinal ischemia patients, respectively. Since plasmin may control TGF-beta activation, the serum protein alpha2-antiplasmin was measured and found to be significantly elevated to 150 and 250% of control values in PDR and ischemia patients, respectively. Thus, influx of serum proteins due to microvascular disturbances and hypoxia is proposed as a possible cause for vitreous alterations of IGF-I and of active TGF-beta. These changes seem to occur late in the sequence of events leading to PDR and are not specific for diabetes, but they were also observed in other diseases characterized by retinal hypoxia.
Diabetes 1997 Sep
PMID:Growth factor alterations in advanced diabetic retinopathy: a possible role of blood retina barrier breakdown. 928 95

Insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF) levels are correlated with retinal ischemia-associated intraocular neovascularization in humans. Since VEGF is required for iris and retinal neovascularization in animal models of retinal ischemia, we tested whether IGF-I could act as an indirect angiogenic factor by increasing VEGF gene expression. IGF-I increased retinal pigment epithelial (RPE) cell VEGF mRNA in a concentration-dependent manner with an EC50 of 7 nmol/1 (53.6 ng/ml). RPE and bovine smooth muscle cells exposed to 50 nmol/l (383 ng/m1) IGF-I achieved peak VEGF mRNA expression within 2 h. IGF-I-treated RPE cells increased VEGF protein levels in conditioned media and stimulated capillary endothelial cell proliferation. Blockade of the IGF-I receptor with a neutralizing antibody abrogated the VEGF increases in RPE cells. Further, hypoxia-mediated and IGF-I-mediated increases in VEGF mRNA and protein levels were additive in RPE cells, and the hypoxia-induced VEGF increases were independent of endogenous IGF-I. VEGF promoter activity was enhanced by IGF-I in RPE cells, but VEGF transcript half-life was unaltered. In summary, the supplementation of RPE and smooth muscle cell cultures with IGF-I at 5-100 nmol/l increased VEGF mRNA and secreted protein levels. The VEGF increases in RPE cells occurred primarily through enhanced transcription of the VEGF gene and via the IGF-I receptor. Elevated IGF-I levels may promote neovascularization through increased retinal VEGF gene expression.
Diabetes 1997 Oct
PMID:Regulation of vascular endothelial growth factor expression by insulin-like growth factor I. 931 59

Insulin-like growth factor I (IGF-1) is trophic to sensory, motor and sympathetic neurons. Intrathecal (i.t.) administration of IGF-1 produced analgesic effects when tail flick/withdrawal latency was used as an indicator. This action was blocked by genistein (an inhibitor of tyrosine kinase) but not by atipamezol (an alpha2 adrenoreceptor antagonist), naloxone (an opioid antagonist) or glibenclamide (a blocker of ATP sensitive K+ channels). Induction of diabetes with streptozotocin (STZ, 55 mg/kg, i.v.) impaired the ability of IGF-1 to elevate nociceptive threshold. This phenomenon was not seen in normal animals rendered hyperglycemic with D-glucose (20 mmol in 2.5 ml of saline, i.p.). PCR-based assay revealed that the lumbar region of the spinal cord expresses mRNA transcripts for IGF-1 and its receptor. The rates of expression of both of these transcripts were reduced during diabetes. The above behavioral and biochemical abnormalities induced by the diabetic state were partially restored following replacement therapy with insulin. Overall, our data suggest that a receptor-linked tyrosine kinase mediates the antinociceptive effect of IGF-1. Additionally, the attenuation in the ability of IGF-1 to elevate nociceptive threshold may be a consequence of reduced gene expression of IGF-1 receptor within the spinal cord.
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PMID:Attenuation of IGF-1 antinociceptive action and a reduction in spinal cord gene expression of its receptor in experimental diabetes. 953 75

Insulin-like growth factor I (IGF-I) is a ubiquitous endocrine, paracrine and autocrine polypeptide, which influences cell proliferation and differentiation in many tissues. Classically, IGF-I has been tied to growth hormone (GH) and has often been considered a surrogate marker of overall GH status. The advent of recombinant technology has made possible studies of GH and IGF-I for the treatment of chronic diseases (such as diabetes mellitus, osteoporosis and muscle atrophy) as well as to forestall the aging process. Examples of currently active areas of research include efforts to define the involvement of IGF-I physiology in bone remodeling, atherosclerosis and neoplasia. Recent epidemiological evidence suggests that individuals with IGF-I levels in the 'high normal' range have increased risk of common cancers relative to individuals with levels in the 'low normal' range. These findings have focused renewed attention on the genetic and non-genetic determinants of serum IGF-I levels. It is unlikely that the serum IGF-I level itself is related directly to risk of neoplasia, but it may serve as a surrogate for a variable that is important in epithelial cell carcinogenesis, such as rate of epithelial cell proliferation. We review relatively new data suggesting that adult serum IGF-I levels are under the control of heritable factors apart from GH. Such factors may influence tissue expression of IGF-I as well as serum IGF-I levels, and influence a number of clinically important outcomes, including bone density and risk of neoplasia. The concept that there is little physiological importance in the heterogeneity between individuals regarding IGF-I levels within the broad 'normal' range may require re-assessment.
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PMID:Circulating IGF-I: New Perspectives for a New Century. 1032 7


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