Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mesenteric arteries were isolated from the spontaneous diabetic BB rats, non diabetic BB rats and regular Wistar control rats. Gross morphology indicated that the mesenteric vascular bed of the control Wistar rats had a normal development of mesenteric fat pad around the vessels, while that of the diabetic BB rats showed drastically reduced perivascular fat pad, suggesting greater mobilization of fat for energy consumption in the hyperglycemic state of diabetes mellitus. The perivascular mesenteric fat pad of the non-diabetic BB rats was intermediate between those of the Wistar control and diabetic BB rats. The wet weight of the mesenteric arteries following removal of fat, vein and connective tissues was significantly greater in diabetic BB rats than in the corresponding controls. Microsomal membranes isolated from the mesenteric arteries of diabetic BB rats showed increased alkaline phosphatase and 5'-nucleotidase activities compared to those isolated from the two groups of non-diabetic control rats. Acid phosphatase activities were higher in both BB rat groups compared to the Wistar group. The total Ca2+ uptake by the microsomes of mesenteric arteries in the presence of ATP was not different among three experimental groups, but the ATP dependent active transport of Ca2+ was significantly increased and the passive Ca2+ binding was significantly reduced in diabetic group compared to the other two non-diabetic groups. Our results demonstrate that in the spontaneously diabetic BB rats, alterations in both structural and functional parameters may underline the vascular complications associated with type I diabetes mellitus in humans.
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PMID:Membrane abnormalities of vascular smooth muscle of mesenteric arteries of spontaneous diabetic BB rats. 1059 73

This study was performed to clarify if diabetic complications are associated with liver enzyme activities in type 1 diabetic outpatients. Elevated activities of serum aminotransferases are a common sign of liver disease and are observed more frequently among people with diabetes than in the general population. Many studies have shown an association between specific diabetic complications and disturbances in various tissues, such as diabetic nephropathy and cardiovascular diseases, but only limited data are available on the possible association between diabetic complications and liver function. We studied 28 patients with type 1 diabetes. Mean age was 43.4+/-9.5 (S.D.), and duration of diabetes 25.2+/-9.7. Limited joint mobility (LJM) was assessed by the Rosenbloom's method. Background and proliferative retinopathy, and peripheral symmetrical polyneuropathy were also assessed. Activities of alanine amino transferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) in serum were determined. The metabolic control of the diabetes was evaluated by the glycosylated haemoglobin A(1c) (HbA(1c)) level and lipid values were also measured. ALT activity was associated with LJM (P<0.01) and with neuropathy (P<0.01). Association between GGT activity and LJM (P<0.01) and neuropathy (P<0.01) were also found. GGT activity was also associated with the severity of retinopathy (P<0.01). None of these associations was explained by confounding effects of diabetes duration, age, body mass index (BMI), HbA(1c) or alcohol consumption. In conclusion, diabetic complications such as LJM, retinopathy and neuropathy are associated with liver enzyme activities independent of alcohol consumption, BMI and metabolic control of diabetes.
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PMID:Diabetic complications are associated with liver enzyme activities in people with type 1 diabetes. 1131 65

Type 1 diabetic individuals are known to develop disorders of bone metabolism resulting in osteopenia. Previous studies have suggested an influence of vitamin D receptor alleles on bone metabolism and susceptibility for type 1 diabetes mellitus. The present study was initiated to investigate the distribution of vitamin D receptor alleles in Caucasian type 1 diabetic patients and their relation to bone turnover parameters. 75 patients were included and compared to 57 healthy controls. Three vitamin D receptor alleles were examined (BsmI, TaqI and FokI); serum levels of intact osteocalcin, parathyroid hormone, bone specific alkaline phosphatase, the carboxy terminal extension peptide of type I procollagen, 25-OH-vitamin D levels, HbA1c and urinary deoxypyridinoline excretion were measured. We observed a higher frequency of the TT genotype in diabetic patients, but no difference in markers of bone turnover between diabetics and non-diabetics in either sex. Bone turnover was different in men and in women without any association with vitamin D receptor genotype. No association was found between diabetes duration, age of onset or metabolic control and bone turnover parameters. In summary, our results show an association between the TT genotype and diabetes in Germans, but no difference in bone turnover markers between diabetics and non-diabetics.
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PMID:VDR gene polymorphisms are overrepresented in german patients with type 1 diabetes compared to healthy controls without effect on biochemical parameters of bone metabolism. 1217 74

We used NOD mice to investigate the effects of injecting transduced lymphocytes on insulitis, nonfasting blood glucose levels, and immune responses. Syngeneic splenocytes were transduced with retroviral particles carrying a cDNA construct encoding the beta cell antigen glutamic acid decarboxylase (GAD65), a secreted form of GAD65 (SGAD55), or secreted alkaline phosphatase (SEAP) as a control antigen. Different multiplicities of infection (m.o.i.) were used with different constructs. Four-week-old NOD mice received intravenous injection of CD4(+) cells isolated from transduced splenocytes, and insulitis and blood glucose levels were determined at 10 weeks of age. No significant effects were observed with lymphocytes transduced with gad65 and sgad55 constructs at low m.o.i. By contrast, at high m.o.i., lymphocytes transduced with the sgad55 and seap constructs caused a decrease in insulitis and blood glucose levels and in insulitis alone, respectively. ELISA of anti-GAD antibody isotypes indicated that GAD-transduced lymphocytes induced similar Th2-like responses at all m.o.i. These results suggest that retroviral particles carrying sgad55 can be used for engineering cell vaccines for type 1 diabetes and provide further evidence that Th2-like responses induced by immunization may not always be a primary cause of diabetes suppression in NOD mice.
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PMID:Decreased insulitis and blood glucose levels after injection of GAD-transduced lymphocytes into NOD mice. 1249 66

Although osteoporosis is reported as a potential complication of type 1 diabetes mellitus (DM), the effects of type 2 DM on bone mass are conflicting. Most of the studies conducted in recent years reveal that bone mineral density (BMD) values of type 2 DM patients are not decreased and even increased when compared with healthy control groups. In this study we evaluated bone turnover in 57 postmenopausal type 2 DM patients utilizing biochemical markers for bone formation and resorption, and BMD measurements. We found that BMD values in diabetic patients (0.91 +/- 0.11 g/cm(2) for lumbar region, 0.89 +/- 0.14 g/cm(2) for hip region) were higher than healthy postmenopausal control group (0.81 +/- 0.12 g/cm(2) for lumbar region, 0.76 +/- 0.10 g/cm(2) for hip region). Serum alkaline phosphatase values were similar to the control group, whereas serum osteocalcin and N-telopeptide/creatinine (NTx/Cr) values were significantly lower than the control group (osteocalcin: 8.82 +/- 4.03 ng/ml, NTx/Cr: 122.70 +/- 81.76 nMBCE/mMCr) in diabetic patients (osteocalcin: 4.44 +/- 3.53 ng/ml, NTx/Cr: 42.24 +/- 29.97 nMBCE/mMCr). Also a significant correlation was observed between body mass index and BMD values. Our findings suggested that the bone turnover rate is remarkably lower in type 2 DM patients compared to healthy postmenopausal patients.
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PMID:Evaluation of bone turnover in postmenopausal patients with type 2 diabetes mellitus using biochemical markers and bone mineral density measurements. 1272 15

In this study, we aimed to compare bone calcium system changes from children with diabetic ketoacidosis or acute metabolic acidosis due to dehydration to find out the relative contribution of metabolic acidosis and diabetes-related factors on expected negative calcium balance. We studied a set of non-invasive parameters of bone remodeling in 16 children with diabetic ketoacidosis due to new onset type 1 diabetes and 25 children with acute metabolic acidosis due to dehydration complicating acute gastroenteritis before and after the correction of acidosis. The two groups of subjects were matched for age, sex, pubertal status, and degree of metabolic acidosis and dehydration. A group of 18 age and sex-matched healthy children served as the control group. Plasma ionized calcium levels were increased in both groups, significantly more so in diabetic ketoacidosis. While osteoblastic markers, osteocalcin and alkaline phosphatase, were depressed to a comparable degree in both groups, urinary calcium/creatinine ratio and hydroxyproline excretion were significantly greater in diabetic ketoacidosis. No significant changes in calcitrophic hormone (intact PTH, calcitonin, 25-hydroxy vitamin D3) levels were observed. All study parameters except for serum phosphate levels behaved in parallel in both clinical conditions, and abnormalities disappeared with the correction of acidosis except for IGF-1, which remained low in diabetic subjects. In conclusion, our results suggest that, in diabetic ketoacidosis, the observed severe negative calcium balance occurred through diminished bone formation mediated by metabolic acidosis per se and increased bone mineral dissolution and bone resorption because of severe insulin deficiency and secondarily via metabolic acidosis. Observed changes appear to be independent of calcitrophic hormones.
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PMID:Bone calcium changes during diabetic ketoacidosis: a comparison with lactic acidosis due to volume depletion. 1586 25

Decreased bone mass, osteoporosis, and increased fracture rates are common skeletal complications in patients with insulin-dependent diabetes mellitus (IDDM; type I diabetes). IDDM develops from little or no insulin production and is marked by elevated blood glucose levels and weight loss. In this study we use a streptozotocin-induced diabetic mouse model to examine the effect of type I diabetes on bone. Histology and microcomputed tomography demonstrate that adult diabetic mice, exhibiting increased plasma glucose and osmolality, have decreased trabecular bone mineral content compared with controls. Bone resorption could not completely account for this effect, because resorption markers (tartrate-resistant acid phosphatase 5b, urinary deoxypyridinoline excretion, and tartrate-resistant acid phosphatase 5 mRNA) are unchanged or reduced at 2 and/or 4 wk after diabetes induction. However, osteocalcin mRNA (a marker of late-stage osteoblast differentiation) and dynamic parameters of bone formation were decreased in diabetic tibias, whereas osteoblast number and runx2 and alkaline phosphatase mRNA levels did not differ. These findings suggest that the final stages of osteoblast maturation and function are suppressed. We also propose a second mechanism contributing to diabetic bone loss: increased marrow adiposity. This is supported by increased expression of adipocyte markers [peroxisome proliferator-activated receptor gamma2, resistin, and adipocyte fatty acid binding protein (alphaP2)] and the appearance of lipid-dense adipocytes in diabetic tibias. In contrast to bone marrow, adipose stores at other sites are depleted in diabetic mice, as indicated by decreased body, liver, and peripheral adipose tissue weights. These findings suggest that IDDM contributes to bone loss through changes in marrow composition resulting in decreased mature osteoblasts and increased adipose accumulation.
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PMID:Increased bone adiposity and peroxisomal proliferator-activated receptor-gamma2 expression in type I diabetic mice. 1590 21

Insulin dependent diabetes mellitus (IDDM; type I) is a chronic disease stemming from little or no insulin production and elevated blood glucose levels. IDDM is associated with osteoporosis and increased fracture rates. The mechanisms underlying IDDM associated bone loss are not known. Previously we demonstrated that osteoblasts exhibit a response to acute (1 and 24 h) hyperglycemia and hyperosmolality. Here we examined the influence of chronic hyperglycemia (30 mM) and its associated hyperosmolality on osteoblast phenotype. Our findings demonstrate that osteoblasts respond to chronic hyperglycemia through modulated gene expression. Specifically, chronic hyperglycemia increases alkaline phosphatase activity and expression and decreases osteocalcin, MMP-13, VEGF and GAPDH expression. Of these genes, only MMP-13 mRNA levels exhibit a similar suppression in response to hyperosmotic conditions (mannitol treatment). Acute hyperglycemia for a 48-h period was also capable of inducing alkaline phosphatase and suppressing osteocalcin, MMP-13, VEGF, and GAPDH expression in differentiated osteoblasts. This suggests that acute responses in differentiated cells are maintained chronically. In addition, hyperglycemic and hyperosmotic conditions increased PPARgamma2 expression, although this increase reached significance only in 21 days chronic glucose treated cultures. Given that osteocalcin is suppressed and PPARgamma2 expression is increased in type I diabetic mouse model bones, these findings suggest that diabetes-associated hyperglycemia may modulate osteoblast gene expression, function and bone formation and thereby contribute to type I diabetic bone loss.
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PMID:Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways. 1661 59

The long-term potential to routinely use replacement beta cells/islets as cell therapy for type 1 diabetes relies on our ability to culture such cells/islets, in vitro, while maintaining their functional status. Previous beta cell studies, by ourselves and other researchers, have indicated that the glucose-stimulated insulin secretion (GSIS) phenotype is relatively unstable, in long-term culture. This study aimed to investigate phenotypic and gene expression changes associated with this loss of GSIS, using the MIN-6 cell line as model. Phenotypic differences between MIN-6(L, low passage) and MIN-6(H, high passage) were determined by ELISA (assessing GSIS and cellular (pro)insulin content), proliferation assays, phase contrast light microscopy and analysis of alkaline phosphatase expression. Differential mRNA expression was investigated using microarray, bioinformatics and real-time PCR technologies. Long-term culture was found to be associated with many phenotypic changes, including changes in growth rate and cellular morphology, as well as loss of GSIS. Microarray analyses indicate expression of many mRNAs, including many involved in regulated secretion, adhesion and proliferation, to be significantly affected by passaging/ long-term culture. Loss/reduced levels, in high passage cells, of certain transcripts associated with the mature beta cell, together with increased levels of neuron/glia-associated mRNAs, suggest that, with time in culture, MIN-6 cells may revert to an early (possibly multi-potential), poorly differentiated, 'precursor-like' cell type. This observation is supported by increased expression of the stem cell marker, alkaline phosphatase.
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PMID:Phenotypic and global gene expression profile changes between low passage and high passage MIN-6 cells. 1717 Feb 23

It is well known that patients with type 1 diabetes mellitus exhibit bone abnormalities as one of the complications of the disease. Whether this occurs in type 2 diabetes is controversial. This uncertainty could be because type 2 diabetes includes several pathological types such as obese and non-obese. To examine the bone abnormalities in non-obese type 2 diabetes, we used Spontaneously Diabetic Torii (SDT) rats, which is a newly established model of non-obese type 2 diabetes. Sprague-Dawley (SD) rats were used as a control group (n=17). SDT rats were divided into two groups: the diabetic (DM) group (n=18) and the DM+insulin (INS) group (n=18) at 20 weeks of age. The DM+INS group received subcutaneously implanted insulin pellets every 2 weeks. At 36 weeks of age, the rats were killed, and we evaluated bone formation and the effect of insulin on bone formation, blood and urine analyses, bone mineral density (BMD), histomorphometry, and mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN). Despite renal function not being impaired, BMD and bone strength were significantly lower in the DM group than in the control group. Osteoid volume per bone volume, osteoblast surface per bone surface, eroded surface per bone surface, osteoclast surface per bone surface, the mineral apposition rate, and the bone formation rate per bone surface were significantly lower in the DM group than in the control and DM+INS groups. The mRNA expression of ALP and OCN was significantly lower in the DM group than in the control group. Furthermore, 8-hydroxydeoxyguanosine, which is an oxidative stress marker, was remarkably elevated in the DM group. These abnormalities were recovered by insulin therapy. Our data support the notion that non-obese type 2 diabetes is associated with a low turnover of bone and that the abnormalities are ameliorated by insulin. The SDT rat may be a useful animal model for examining the mechanisms of bone abnormalities in non-obese type 2 diabetes.
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PMID:Bone formation in spontaneously diabetic Torii-newly established model of non-obese type 2 diabetes rats. 1803 64


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