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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac microtubule stability is increased in the streptozotocin (STZ) model of type 1 diabetes. Here, we investigate the reason for increased microtubule stability, and the functional consequences of stable microtubule disruption. Ventricular myocytes were isolated from rats at 8-12 weeks after injection of STZ. A 10% increase in microtubule density, but no difference in the ratio of microtubule-associated protein 4 (MAP4) to tubulin was seen in myocytes from STZ rats. Functionally, STZ myocytes showed a tendency for reduced shortening and intracellular Ca2+ ([Ca2+]i) transient amplitude, and a significant prolongation of time to peak (ttp) shortening and [Ca2+]i. Although microtubules in STZ myocytes were less sensitive to the microtubule disruptor nocodazole (NOC; 33 microM) than control myocytes, we only saw marked functional consequences of microtubule disruption by NOC in myocytes from diabetic animals. NOC increased shortening and [Ca2+]i transient amplitude in STZ myocytes by 45 and 24%, respectively (compared with 4 and 6% in controls). Likewise, NOC decreased ttp shortening and [Ca2+]i only in STZ myocytes, such that these parameters were no longer different between the two groups. In conclusion, stable microtubules in diabetes are not associated with an increase in MAP4, but are functionally relevant to cardiac dysfunction in diabetes, regulating both [Ca2+]i and shortening.
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PMID:Stable microtubules contribute to cardiac dysfunction in the streptozotocin-induced model of type 1 diabetes in the rat. 1683 7

Diabetes mellitus is associated with various organ dysfunctions through hyperglycemia, insulin deficiency, or advanced glycation end products, which can also cause impaired calcium homeostasis such as the reductions of parathyroid hormone secretion, vitamin D receptor (VDR) number, and 25- (OH) vitamin D-1 alpha-hydroxylase activity in the parathyroid gland, intestine, and kidney, respectively. On the contrary, abnormal calcium homeostasis such as vitamin D deficiency/insensitivity and hyperparathyroidism can cause glucose intolerance or diabetes. Vitamin D deficiency/insensitivity induces type 2 diabetes through impaired insulin secretion involving VDR on pancreatic beta cells, as well as type 1 diabetes through the reduction in immuno-modulatory action of 1,25 (OH)(2) vitamin D. Primary hyperparathyroidism induces glucose intolerance via insulin resistance due to elevated intracellular calcium in the targeted organ of insulin.
Clin Calcium 2006 Aug
PMID:[Calcium homeostasis and diabetes mellitus]. 1688 34

Although the clinical manifestations of diabetic osteopahty are not fully elucidated, diabetes may affect bone remodeling by various mechanisms, including deficiency of insulin actions, increased accumulation of advanced glycation end products and microangiopahty. The combination of subsequent poor bone quality of micro- or nano-architecture and frequent injurious falls would be related to an increase of fracture incidence. Several recent reports have revealed that older women with diabetes had a particularly increased risk of fractures. Bone mineral density (BMD) is the best predictor for fractures of primary osteoporosis, and increased risk for fractures of the type 1 diabetes is associated with the decrease of BMD, but not on the type 2 diabetes. The patients frequently show an increase of BMD, but suffer from fractures. At present, there is mostly no data what kind of intervention or pharmaceutical therapy is the best to avoid the incidence. Some in vivo studies support that vitamin K(2) (menatetrenone) may ameliorate bone quality damage in diabetics.
Clin Calcium 2006 Aug
PMID:[Therapeutic approaches for diabetic osteopahty]. 1688 37

Osteopenia was reported in patients with type I diabetes mellitus (DM). Also, serum levels of advanced glycation endproducts (AGEs) were reported to be elevated in DM. In this review, we showed the effect of AGEs on primary human osteoblasts, the precursor of human osteoclast like cells and parathyroid cells in culture. AGEs were made from incubating bovine serum albumin with glucose 6 phosphate for 8 weeks (AGEs-BSA). AGEs-BSA (1,000 microg/mL) showed inhibitory effect for human osteoblasts in terms of the productions of procolagen c propeptide and osteocalcin, which were regarded as bone forming parameters. On the other hand, the same concentration of AGEs-BSA inhibited the increase in the parathyroid hormone secretion from the cultured human parathyroid cells induced by low calcium medium concentration. AGEs-BSA increased time dependently intracellular calcium levels of HEK 293 cells, which expressed the wild type human calcium-sensing receptor. Also, AGEs-BSA increased IL-6 synthesis by primary human osteoblast. Our preliminary data also showed that AGEs-BSA increased osteoclast-like cells formation in number from the osteoclast precursor rich bone marrow cells. These data suggested the important role of AGEs for the pathogenesis of osteopenia in patients with DM through decreased bone formation and increased bone resorption.
Clin Calcium 2006 Aug
PMID:[The role of AGEs for the pathogenesis of osteopenia in diabetes mellitus]. 1688 40

Endocrinology has recently witnessed several important developments: The Epidemiology of Diabetes Interventions and Complications study, a follow-up to the landmark Diabetes Control and Complications trial, found that strict glucose control early in the course of type 1 diabetes reduces the risk of microvascular and cardiovascular complications and provides prolonged benefits even if intensive control is not so tightly maintained. Inhaled insulin preparations are now available for mealtime coverage. We now have two new injectable medications for diabetes; pramlintide (Symlin) and exenatide (Byetta) are good adjuncts for patients with both type 1 and type 2 diabetes who have trouble reaching their hemoglobin A1c target, and they can help control and even reduce weight. Thyroxine (T4), instead of being merely a "prohormone," has been found to have direct actions on cells, leading to rapid clinical effects and possibly oncogenesis and angiogenesis. The therapeutic range for thyrotropin (TSH) may be much narrower than traditionally believed: some have proposed that the normal range should be redefined as 0.4 to 2.5 mIU/L. New evidence shows that vitamin D is important for more than calcium control and may help prevent type 1 diabetes.
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PMID:Endocrinology update 2006. 1712 44

Vitamin D has been involved in the modulation of calcium and bone metabolism as well as in the immune system, where it suppresses the proliferation of activated T cells. These effects are exerted via the vitamin D receptor (VDR). Polymorphisms within this gene have been exhaustively studied in diverse autoimmune diseases but with inconsistent results. We previously reported a positive association of polymorphisms within the VDR gene (Apa I, Taq I, Bsm I, and Fok I). In the present article we extended our previous reports to seven additional polymorphisms (rs757343, rs9729, rs2853559, rs1989969, rs3847987, rs2238135, and rs4516035) in a larger set of German simplex type 1 diabetes families. Additionally we correlated serum levels of 25(OH)D(3) and 1,25(OH)(2)D(3) with VDR genotypes and haplotypes. The haplotypes "CG" (Taq I-Apa I), "CGG" (Taq I-Apa I-Tru I), "CGC" (Taq I-Apa I-Fok I), "GCTG" (rs9729-Taq I-Apa I-Tru I), and "CGGC"(Taq I-Apa I, Tru I, Fok I) were less often transmitted, thus negatively associated with type 1 diabetes. Patients who carried the genotype "CC" of the rs3847987 polymorphism had higher median serum levels of 25(OH)D(3). Furthermore, the majority of patients with this genotype possessed normal serum levels of 25(OH)D(3). We conclude that variants of the VDR may confer a genetic protection from type 1 diabetes. Furthermore, normal serum levels of 25(OH)D(3) appear to correlate with a VDR genotype. This supports a role of vitamin D in the immune pathogenesis of type 1 diabetes.
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PMID:Protection from type 1 diabetes by vitamin D receptor haplotypes. 1713 May 74

Neonatal hypoglycemia is a frequent event in the first hours of life of newborns from mothers with diabetes mellitus. We studied a group of diabetic mothers newborns during the first day of life, taking venous blood samples at < 6 h, 6-12 h and 12-24 h of life for glucose analysis (n = 85), defining hypoglycaemia as a glucose level < 35 mg/dL. Calcium serum levels were also determined in the first venous sample in 19 neonates and 7 mEq/L was the criteria for hypocalcemia. The mothers age (mean +/- standard deviation) was 30.5 +/- 5.5 years (range 16-41 years), 43 (50.6%) of them with gestational diabetes, 40 (47.1%) with type 2 diabetes and 2 (2.4%) with type 1 diabetes. Pregnancies ended by caesarean section in 78 (91.8%) and by partum in seven (8.2%) women. There were 20 (23.5%) preterm newborns. In relation to neonates weight, 27 (31.7%) were macrosomic and 7 (8.2%) were premature, two of them with very low weight. A total of 55 (64.77%) newborns had hypoglycaemia, but only one of them had a convulsive episode, the rest were asymptomatic. In relation to the newborns weight, 18 (66.6%) of the macrosomic, 33 (64.7%) of the normal weight and four (57.1%) of the premature groups had hypoglycaemia. The comparisons between the newborns weight groups showed non significant differences, but the prevalence of neonatal hypoglycaemia was significantly higher in the group of gestational diabetes than in the type 2 diabetes group (p < 0.05). Calcium analysis also disclosed asymptomatic hypocalcemia in five (7.25%) newborns. These results show an elevated prevalence of asymptomatic neonatal hypoglycaemia in the offspring of women with diabetes mellitus in their early hours of life, and stress the importance of systematic glucose monitoring and early treatment in the first hours of life of these neonates.
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PMID:[Hypoglycemia in the newborns of women with diabetes mellitus]. 1714 39

Cations play major physiological and biochemical roles in the excitation-contraction coupling processes in the heart. This study investigated the effect of streptozotocin (STZ)-induced type I diabetes mellitus (DM) on contraction, calcium transient [Ca2+]i, and cation contents in the isolated rat heart compared to age-matched control. Diabetes rats weighed significantly (P < 0.05) less compared to control. They also had significantly (P < 0.05) elevated blood glucose compared to control. The whole heart, as well as the atria, right and left ventricles of the diabetic heart weighed significantly (P < 0.05) less compared to hearts from age control rats. The force of contraction and time to peak (t-pk) contraction in diabetic ventricular myocytes increased significantly (P < 0.05) compared to control. By contrast, these parameters did not change for the Ca2+ transient except for the time to half (t(1/2)) relaxation. The levels of sodium (Na+), potassium (K+), calcium (Ca2+), magnesium (Mg2+), iron (Fe2+), copper (Cu2+), and zinc (Zn2+) in the hearts varied from diabetic compared to control animals. The results indicate that 6-8 weeks of STZ-induced DM is associated with marked changes in contraction and in cation contents of the heart. The delay in the t(1/2) relaxation of the Ca2+ transient may be responsible for the elevated contraction seen in the diabetic heart. Moreover, the changes in cation contents in the heart may be responsible for abnormal cardiac rhythms and activity during DM.
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PMID:Effect of streptozotocin-induced type 1 diabetes mellitus on contraction, calcium transient, and cation contents in the isolated rat heart. 1715 1

This study investigated the effect of streptozotocin (STZ)-induced type 1 diabetes mellitus (DM) on total protein concentration and levels of sodium (Na+), potassium (K+), magnesium (Mg2+), zinc (Zn2+), copper (Cu2+), calcium (Ca2+), and iron (Fe2+) in the pancreas, parotid, submandibular, and lacrimal glands of the rat, compared to age-matched control animals. Protein concentrations were measured by the Bradford Assay, whereas levels of Na+, K+, Mg2+, Zn2+, Cu2+, Ca2+, and Fe2+ were measured by flame photometry and atomic absorbance spectrophotometry. The results show marked changes in the characteristics of diabetic and control animals. Diabetic rats and their different glands weighed significantly (P < 0.05) less compared to age-matched controls. Diabetic rats also have significantly elevated blood glucose and significantly reduced plasma insulin, compared to controls. The results also show that the concentrations of proteins and levels of cations were significantly (P < 0.05) reduced in the pancreas, parotid, submandibular and lacrimal glands of diabetic rats, compared to glands from age-matched animals. These differences in the cation contents and protein levels in STZ-induced DM in this study, along with supporting evidences from previous studies, may provide evidence for the development of long-term complications of DM including exocrine gland deficiencies.
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PMID:Effects of streptozotocin-induced type 1 diabetes mellitus on total protein concentrations and cation contents in the isolated pancreas, parotid, submandibular, and lacrimal glands of rats. 1715 25

Bladder dysfunction is a common complication of diabetic autonomic neuropathy; however, its cause remains uncertain. We have recently identified a novel IgG autoantibody (Ab) in patients with type 1 diabetes that acts as an agonist at the dihydropyridine (DHP) site of L-type voltage-gated calcium channels (VGCC), disrupting neuronal regulation of visceral smooth muscle. In the present study, passive transfer to mice of IgG from patients with type 1 diabetes was used to investigate the role of anti-VGCC Abs in mediating diabetic bladder dysfunction. Injection of mice with diabetic immunoglobulin (IgG) with anti-VGCC activity induced features of an overactive bladder, including phasic detrusor contractions and a loss of bladder wall compliance. The bladder overactivity is mimicked by the DHP agonist Bay K8644, reversed by the DHP antagonist nicardipine, but is insensitive to the motor nerve blocker tetrodotoxin, indicating that the anti-VGCC Ab acts at the level of the bladder detrusor itself. This study reports the first evidence of Ab-mediated bladder dysfunction in type 1 diabetes, which may be part of a wider spectrum of smooth muscle and cardiac abnormalities.
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PMID:Autoantibody-mediated bladder dysfunction in type 1 diabetes. 1721 69


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