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

Insulin resistance characterizes non-insulin dependent diabetes (NIDDM). Insulin resistance may coexist in clinical syndromes with hyperestrogenism and hyperandrogenism, suggesting that the ovary may be sensitive to effects of insulin. In addition, insulin-like growth factor-I receptors, which are capable of binding insulin, have been identified in ovarian cancer tissue and are proposed to regulate cell growth. We evaluated the association between a history of diabetes mellitus and ovarian cancer in a case-control study in seven counties in Washington and in Utah (United States) during the years 1975-87. Cases included women newly diagnosed with ovarian cancer over a five-year period who were identified through population-based cancer reporting. Controls similar to cases with regard to age and county of residence were identified via household surveys or random digit dialing. The study included 595 cases and 1,587 controls. Twenty-seven cases (4.5 percent) and 72 controls (4.5 percent) reported a history of diabetes. Logistic regression analysis of the association between diabetes and ovarian cancer controlling for age, body mass index, and race resulted in an odds ratio (OR) of 0.9 (95 percent confidence interval [CI] = 0.6-1.5). The OR was not changed with further controlling for prior oral contraceptive use or prior pregnancy. None of the 20 women with nonepithelial tumors (15 of which were stromal tumors) had a history of diabetes (upper CI = 4.0). These results, together with findings of two earlier cohort studies, do not support the hypothesis that diabetes is a risk factor for epithelial ovarian cancer.
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PMID:Is diabetes mellitus a risk factor for ovarian cancer? A case-control study in Utah and Washington (United States). 881 36

Plasma prorenin and renin, serum insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP-2 and IGFBP-3) concentrations were measured in 22 randomly selected male and female patients with insulin-dependent diabetes mellitus (IDDM) or non-IDDM (NIDDM). Plasma prorenin concentration was significantly elevated in patients with proliferative retinopathy (1869.5 +/- 785.0 mUL-1, mean +/- SEM) compared to patients with nonproliferative retinopathy (325.5 +/- 73.2 mUL-1, P < 0.003) and those without retinopathy (318.6 +/- 47.3 mUL-1, P < 0.007). Similarly, serum insulin-like growth factor-I (IGF-I) concentration in patients with proliferative retinopathy (126.3 +/- 21.5 micrograms L-1) was significantly higher than in patients with nonproliferative retinopathy (126.3 +/- 14.85 micrograms L-1, P < 0.004) and without retinopathy (135.2 +/- 37.26, P < 0.05). There was moderately strong positive correlation between plasma prorenin and serum IGF-I concentrations (r = 0.56, P < 0.01). Plasma prorenin concentration was uninfluenced by change in renal function (creatinine clearance, serum creatinine or BUN), but IGF-I levels were inversely related to creatinine clearance (r = 0.67, P < 0.002). There was no demonstrable relationship between IGF-binding proteins and prorenin or renin concentrations. In view of some overlap between plasma prorenin and serum IGF-I concentrations in diabetic patients with proliferative and nonproliferative retinopathy, measurement of both markers may be more useful in predicting the development of proliferative retinopathy in patients with diabetes mellitus than either measurement alone.
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PMID:Relationship between prorenin, IGF-I, IGF-binding proteins and retinopathy in diabetic patients. 891 51

In the skin of diabetic animal tissues the amount of extracellular matrix (ECM) components is drastically decreased as a result of a reduced rate of their biosynthesis or increased degradation. In the present study we have investigated the mechanism of poor wound healing in diabetic rats. We have found that wounded skin of diabetic rats shows a significant decrease in glycosaminoglycan (GAG) content compared to that of control animals. This decrease was accompanied by significant depletion of insulin-like growth factor-I (IGF-I), known as a stimulator of GAG biosynthesis, and a distinct decrease in the content of high molecular weight IGF-binding proteins (HMW-BPs) with a simultaneous increase in low molecular weight IGF-binding proteins (LMW-BPs) in the sera of diabetic animals. Basing on determination of proteolytic activities we suggest that insulin shortage in diabetes results in increased proteolytic activity in various tissues. Proteolytic enzymes may cleave the HMW-BPs and convert them to LMW-BPs. The LMW-BPs may inactivate IGF-I and eliminate its stimulatory effects on GAG biosynthesis. The proteolytic enzymes may also digest the protein cores of proteoglycans releasing the GAGs and making them more susceptible to the action of glycosidases. These phenomena may be responsible for the observed marked decrease in GAG content in the skin of diabetic rats and disturb the wound-healing process.
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PMID:Alterations in glycosaminoglycans in wounded skin of diabetic rats. A possible role of IGF-I, IGF-binding proteins and proteolytic activity. 892 41

Hypertransfusion therapy has dramatically increased the duration and quality of life in patients with B-thalassemia major; however, it leads to chronic iron overload, and is frequently complicated by the development of diabetes mellitus or impaired glucose tolerance. To determine the early effect of iron overload on the endocrine pancreatic function, we studied glucose, insulin, and glucagon responses to oral load of glucose and to arginine provocation in 15 children with B-thalassemia major, before and after (3.1 +/- 0.6 years) high-transfusion and iron chelation and compared them with 15 age matched normal controls. In addition, we evaluated growth hormone (GH) responses to oral clonidine and measured the circulating insulin-like growth factor-I concentration in thalassemic children on long-term transfusion and controls. After long-term high-transfusion, thalassemic children had significantly decreased serum insulin concentrations and low insulin/glucose ratios at 60 and 120 min after an oral glucose load (1.75 g/kg) in comparison with values before therapy and those for controls. None of the thalassemic children had glucose intolerance after this period of frequent blood transfusion; however, their serum glucose levels at 60 and 120 min after the oral glucose load were significantly higher compared to control children. Thirty minutes after starting arginine infusion, serum insulin concentration was significantly lower in thalassemic children compared to before therapy. Basal and arginine-stimulated glucagon secretions were significantly elevated in thalassemic children on long-term blood transfusion with significantly low serum insulin/glucagon ratios. In addition, the high basal serum glucagon concentrations were not suppressed after the oral glucose load. Despite hyperglucagonaemia in all thalassemic children, their blood glucose dropped appropriately below 50 per cent of the fasting glucose level after an intravenous insulin dose (0.1 U/kg) ruling out any significant insulin-resistance. GH responses to clonidine provocation were subnormal in thalassemic children after long-term blood transfusion compared to controls. In summary, thalassemic children on long-term blood transfusion and iron chelation have progressive and early loss of B-cell mass, manifested by decreased insulin release in response to secretagogues, before the development of significant insulin resistance or impairment of glucose tolerance.
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PMID:Insulin and glucagon responses to provocation with glucose and arginine in prepubertal children with thalassemia major before and after long-term blood transfusion. 893 61

Experimental data support a role for insulin and insulin-like growth factor-I (IGF-I) in the pathophysiology of vascular complications in diabetes. Clinical data for both hormones are less convincing, mainly because the various studies vary in methodologies, sample sizes, and populations. So far, by epidemiological means, insulin's vascular toxicity has been shown only in middle-aged non-diabetic men. Furthermore, serious methodological problems hamper the clear understanding of IGF-I's significance in this context. Definitive determination of the role of insulin, IGFs and other growth factors in the development of diabetic vascular complications needs considerably more work. In any case, hyperinsulinemia is associated with a cluster of other accepted risk factors for cardiovascular disease which altogether resemble the entire insulin-resistance syndrome.
Diabetes Res Clin Pract 1996 Feb
PMID:Insulin and insulin-like growth factor-I: their role as risk factors in the development of diabetic cardiovascular disease. 896

Glucose transport activity in cultured rat vascular smooth muscle cells (VSMCs) was examined under various concentrations of D-glucose, insulin, and insulin-like growth factor-I (IGF-I). Confluent cultures of VSMCs were incubated with serum-free medium containing 0-25 mmol/l of D-glucose for 24-49 h. The basal rate of 2-deoxyglucose uptake was reduced in association with increasing concentrations of D-glucose. Uptake of 2-deoxyglucose into the cells was linear between 0 and 15 min of incubation regardless of the glucose concentration. The uptake was inhibited by the addition of 10 mumol/l cytochalasin B or 100 mmol/l D-glucose indicating that the effects were mediated by specific integral glucose carriers. The effect of D-glucose was time-dependent and reversible. Insulin increased the uptake of 2-deoxyglucose in a dose-dependent manner, and its effect was dependent on the preincubation dose of D-glucose. Insulin-stimulated uptake was lower in the cells pre-exposed to 25 mmol/l D-glucose than in the cells pre-exposed to concentrations of D-glucose below 5.5 mmol/l. After a long-term incubation with insulin, the insulin-stimulated glucose transport was inhibited. Recovery of glucose transport activity was assessed by incubating cells with D-glucose for 24-48 h to induce desensitization. After a 24 h glucose conditioning, the uptake of 2-deoxyglucose was lower in the cells preincubated with 25 mmol/l glucose than in the cells preincubated with 5.5 mmol/l glucose. The effect of the glucose conditioning was reversible and dependent on the preincubation dose of D-glucose. IGF-I was a more potent stimulator of glucose transport than insulin. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), inhibited the uptake of glucose stimulated by insulin or IGF-I in a dose-dependent manner. Our results suggest that D-glucose regulates its own uptake independently of insulin and modulates the ability of insulin to induce insulin resistance in the cultured rat VSMCs. Glucose attenuated the effect of insulin, and led to a progressive decrease in the activity of the glucose transport effector system. Activation of wortmannin-sensitive PI3-kinase may be involved in the signaling pathways of the insulin- and IGF-I-stimulated glucose uptake in VSMCs. This mechanism of insulin resistance may be relevant to the formation of cellular defects in the vascular wall in patients with diabetes mellitus.
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PMID:Effect of glucose, insulin, and insulin-like growth factor-I on glucose transport activity in cultured rat vascular smooth muscle cells. 900 4

Two genes whose expression is likely to be altered during diabetes mellitus are aldose reductase (AD) and insulin-like growth factor-I (IGF-I). We proposed that gene expression of AD is increased in vascular smooth muscle during diabetes mellitus due to hyperglycemia, while IGF-I expression is decreased in insulin-deficient diabetes and elevated in insulin-resistant diabetes. The mRNA for both was measured in the renal glomerulus, in the vascular smooth muscle of large arterioles from the brain, kidney, and small intestine, and in the aorta of hypoinsulinemic streptozotocin (STZ)-treated rats and hyperinsulinemic Zucker diabetic fatty (ZDF) rats. Quantitative in situ hybridization was used to determine variations in expression. Expression of the AD gene was unchanged in STZ and ZDF rats, except for a decrease of about 50% in glomeruli and renal smooth muscle of STZ diabetic rats. Expression of IGF-I generally decreased in vascular smooth muscle of insulin-depleted STZ diabetic rats, but was normal in hyperinsulinemic ZDF rats. The data indicate that decreased expression of the AD gene is a specific problem in renal vascular smooth muscle and glomeruli in the insulin-depleted STZ model of diabetes. The expression of the IGF-I gene in vascular muscle was decreased in hypoinsulinemic diabetic animals, but did not increase in hyperinsulinemic diabetic rats.
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PMID:Aldose reductase and IGF-I gene expression in aortic and arteriolar smooth muscle during hypo- and hyperinsulinemic diabetes. 905 75

Since insulin-like growth factor-I (IGF-I) has been shown to promote renal growth and as kidney IGF-I content increases during the early days after the onset of diabetes, it is likely that this growth factor contributes to initial diabetic renal hypertrophy. However, it is unclear whether IGF-I contributes to the continued renal growth that occurs in diabetes. Since IGF-I action is mediated through its receptor and as its bioavailability is regulated by IGF binding proteins (IGFBP), we postulated that changes in IGF-I receptor binding or IGFBP production may favor a role for IGF-I in diabetic renal growth when kidney IGF-I levels have returned to normal. To test this thesis, we studied kidneys of rats after seven days of streptozotocin diabetes. In diabetic cortex and medulla, growth hormone receptor mRNA levels and IGF-I and IGF-I receptor mRNA and protein product levels were unchanged. In cortex IGFBP-1 mRNA levels were increased while IGFBP-2 and -4 mRNA levels decreased. In medulla the only change was a fall in IGFBP-1 mRNA levels. Using Western ligand blot we observed an increase in a 32 kDa plasma membrane-associated IGFBP. Insulin therapy reversed all changes except the elevated cortical IGFBP-1 mRNA levels, indicating the presence of regional heterogeneity in the IGFBP response to diabetes in the kidney. However, the lack of change in IGF-I, IGF-I receptor and growth hormone receptor gene expression and protein products after one week of diabetes argues against a role for IGF-I in sustaining diabetic renal growth beyond the initial growth phase.
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PMID:Regional changes in the intrarenal insulin-like growth factor-I axis in diabetes. 906 15

We encountered a 91-year-old patient with acromegalic features. The serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) were increased to 23.3 ng/ml and to 268 ng/ml, respectively. Both thyrotropin-releasing hormone and luteinizing hormone-releasing hormone tests demonstrated a 2-3 fold increase in the serum GH level. Magnetic resonance imaging disclosed a pituitary mass in the enlarged sella. The patient was diagnosed as having acromegaly due to overproduction of GH from a pituitary tumor. She manifested cardiac hypertrophy with severe aortic stenosis and mild hypertension, but without diabetes mellitus. After the administration of octreotide subcutaneously at a dose of 25 to 50 micrograms daily for 20 days, the serum GH level increased transiently but decreased rapidly to approximately half the initial level, and suppression of the GH level persisted thereafter for over 2.5 months. This patient seems to be the oldest patient with acromegaly among those reported in Japan.
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PMID:A case report of an elderly patient with acromegaly. 907 12

Transplantation of fetal pancreas (FP) is a potential treatment for diabetes mellitus. FP has remarkable proliferative capacity and may be induced to expand sufficiently to provide a functional beta cell mass in adult recipients. We have demonstrated that local delivery of recombinant insulin-like growth factor-I (IGF-I) onto FP isografts is sufficient to reverse streptozotocin-induced diabetes in animals receiving as few as 4 fetal pancreata. In this current study we investigated other regimens of IGF-I delivery in an attempt to define whether its effects on FP required local delivery or whether other, more clinically feasible, forms of treatment would suffice. In our model, diabetic Lewis rats received isografts of 16 FP into the anterior thigh intramuscular (IM) site. In the group of FP recipients treated with vehicle alone, no animals converted to euglycemia (0/8). When the IM site was pretreated locally with 14 days of continuous IGF-I administration (69 micrograms/kg per day) prior to FP transplantation, 100% of the recipients (10/10) became euglycemic with a mean interval from transplant to euglycemia of 35 +/- 15 days (P < 0.001 when compared to vehicle alone). No significant advantage over the vehicle alone group was gained either when the FP tissue was cultured for 48 hr in the presence of IGF-I (100 micrograms/ml) and then implanted (27% conversion to euglycemia, 3/11) or when FP isografts were treated with continuous subcutaneous delivery of IGF-I (69 micrograms/kg per day over 14 days) distant from the transplant site (0% conversion to euglycemia, 0/6). IGF-I increased the rate of conversion to euglycemia either when delivered locally to FP isografts or when delivered to the transplant bed prior to transplantation. This suggests an active role of the IGF-I-treated transplant bed in the success of FP transplantation.
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PMID:Regimens of IGF-I treatment in fetal pancreas transplantation. 912 98


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