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

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.
 ...
PMID:Bone calcium changes during diabetic ketoacidosis: a comparison with lactic acidosis due to volume depletion. 1586 25

It has been observed anecdotally that diabetics are usually non-ketotic at the time of their seizure presentation. In order to establish some validity on this observation, we reviewed the medical records of patients with diagnoses of diabetes and seizure. Study subjects were diabetics presenting with seizures. Control subjects were random sampling of all diabetics. In 51 diabetics presenting with seizures, 38 were nonketotic and 13 were ketotic. In the control group of 119 diabetics, 63 were non-ketotic and 56 were ketotic. There were no significant differences in the serum levels of glucose, sodium, potassium, chloride, and calcium between the seizure and control groups. Multiple regression analysis showed that non-ketotic patients were at risk for developing seizures with an odds ratio of 4.03 (p=0.001). Male sex and type 1 diabetes were also risk factors while age was not a risk factor. Keto-acidosis may play a role in preventing epileptic seizures from occurring in diabetic patients.
 ...
PMID:Effect of keto-acidosis on seizure occurrence in diabetic patients. 1596 Jan 81

Vitamin D sufficiency is required for optimal health. The conditions with strong evidence for a protective effect of vitamin D include several bone diseases, muscle weakness, more than a dozen types of internal cancers, multiple sclerosis, and type 1 diabetes mellitus. There is also weaker evidence for several other diseases and conditions. There are good reasons that vitamin D sufficiency be maintained during all stages of life, from fetal development to old age. Adequate calcium intake is also recommended. The current vitamin D requirements in the United States are based on protection against bone diseases. These guidelines are being revised upward in light of new findings, especially for soft-tissue health. The consensus of scientific understanding appears to be that vitamin D deficiency is reached for serum 25-hydroxyvitamin D (25OHD) levels less than 20 ng/mL (50 nmol/L), insufficiency in the range from 20-32 ng/mL, and sufficiency in the range from 33-80 ng/mL, with normal in sunny countries 54-90 ng/mL, and excess greater than 100 ng/mL. Solar ultraviolet-B (UVB) irradiation is the primary source of vitamin D for most people. In general, the health benefits accruing from moderate UV irradiation, without erythema or excess tanning, greatly outweigh the health risks, with skin pigmentation (melanin) providing much of the protection. In the absence of adequate solar UVB irradiation due to season, latitude, or lifestyle, vitamin D can be obtained from fortified food, oily fish, vitamin D supplements, and artificial sources of UVB radiation.
 ...
PMID:Benefits and requirements of vitamin D for optimal health: a review. 1598 79

The lymphocyte K+ channel Kv1.3 constitutes an attractive pharmacological target for the selective suppression of terminally differentiated effector memory T (TEM) cells in T cell-mediated autoimmune diseases, such as multiple sclerosis and type 1 diabetes. Unfortunately, none of the existing small-molecule Kv1.3 blockers is selective, and many of them, such as correolide, 4-phenyl-4-[3-(methoxyphenyl)-3-oxo-2-azapropyl]cyclohexanone, and our own compound Psora-4 inhibit the cardiac K+ channel Kv1.5. By further exploring the structure-activity relationship around Psora-4 through a combination of traditional medicinal chemistry and whole-cell patch-clamp, we identified a series of new phenoxyalkoxypsoralens that exhibit 2- to 50-fold selectivity for Kv1.3 over Kv1.5, depending on their exact substitution pattern. The most potent and "drug-like" compound of this series, 5-(4-phenoxybutoxy)psoralen (PAP-1), blocks Kv1.3 in a use-dependent manner, with a Hill coefficient of 2 and an EC50 of 2 nM, by preferentially binding to the C-type inactivated state of the channel. PAP-1 is 23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG, calcium-activated K+ channels, Na+,Ca2+, and Cl- channels. PAP-1 does not exhibit cytotoxic or phototoxic effects, is negative in the Ames test, and affects cytochrome P450-dependent enzymes only at micromolar concentrations. PAP-1 potently inhibits the proliferation of human TEM cells and suppresses delayed type hypersensitivity, a TEM cell-mediated reaction, in rats. PAP-1 and several of its derivatives therefore constitute excellent new tools to further explore Kv1.3 as a target for immunosuppression and could potentially be developed into orally available immunomodulators.
 ...
PMID:Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases. 1609 41

The migration of macrophages and lymphocytes that produce cytokines such as tumor necrosis factor-alpha (TNF-alpha) causes beta-cell death, leading to type 1 diabetes. Similarly, in type 2 diabetes, the adipocyte-derived cytokines including TNF-alpha are elevated in the circulation, causing inflammation and insulin resistance. Thus, the studies described in this article using TNF-alpha are relevant to furthering our understanding of the pathogenesis of diabetes mellitus. We used RINr1046-38 (RIN) insulin-producing beta-cells, which constitutively express calbindin-D(28k), to characterize the effect of TNF-alpha on apoptosis, replication, insulin release, and gene and protein expression. Western blots of TNF-alpha-treated RIN cells revealed a decrease in calbindin-D(28k). By ELISA, TNF-alpha-treated beta-cells had 47% less calbindin-D(28k) than controls. In association with the decline in calbindin-D(28k), TNF-alpha treatment of RIN cells led to a 73% greater increase in changes in intracellular calcium concentration (Delta[Ca(2+)](i)) in TNF-alpha-treated cells as compared to that in control RIN cells upon treatment with 50 mM KCl; caused a greater increase in the [Ca(2+)](i) following the addition of 5.5 microM ionomycin; increased by more than threefold the apoptotic rate, expressed as the percentage of TUNEL-positive nuclei to total nuclei; decreased the rate of cell replication by 36%; and increased and decreased selectively the expression of specific genes as determined by microarray analysis. The subcellular localizations of Bcl-2, an antiapoptotic protein, and Bax, a proapoptotic protein, within RIN cells were altered with TNF-alpha treatment such that the two were colocalized with mitochondria in the perinuclear region. We conclude that the proapoptotic action of TNF-alpha on beta-cells is manifested via decreased expression of calbindin-D(28k) and is mediated at least in part by [Ca(2+)](i).
 ...
PMID:Tumor necrosis factor-alpha-induced changes in insulin-producing beta-cells. 1611 68

Diabetes mellitus and arterial hypertension are the leading causes of end-stage renal disease in industrialized countries. Although attention has focused on renal disease and insulin-dependent diabetes mellitus (type 1 diabetes), a silent epidemic of renal disease caused by type 2, noninsulin-dependent diabetes mellitus is rapidly developing. The course of renal function is heterogeneous in type 2 diabetic patients and reflects heterogeneous patterns of renal lesions. A subset of patients with microalbuminuria and proteinuria is characterized by the typical diabetic glomerulopathy usually observed in type 1 diabetic patients, with altered albumin excretion rate (AER), for example, glomerular basement membrane thickening and mesangial fractional volume expansion. These patients also have diabetic retinopathy and rapidly lose renal function despite tight blood pressure control. In contrast, a second subset of type 2 diabetic patients has normal or near-normal patterns of glomerular structure, despite abnormalities of AER comparable to those of the patients with diabetic glomerulopathy. Thus abnormalities of AER have a different renal prognostic value depending on the underlying renal structure. The patients with worse clinical prognosis and typical diabetic glomerulopathy also have diabetic retinopathy, whereas those with a better course of renal function quite often have no diabetic retinopathy. Several findings, albeit not unanimous, suggest that HbA1c levels above 7.5 to 8.0 % are closely associated with a rapid decay of renal function in type 2 diabetes. Tight blood pressure control plays a further important role in determining the progression of renal a damage in type 2 diabetes mellitus. Convincing evidence has been provided that drugs capable of inhibiting the renin-angiotensin hormonal system are quite effective in preventing and delaying the evolution of renal damage in both type 1 and 2 diabetes. Equally strong data support the view that other antihypertensive compounds such as beta-blockers and calcium antagonists also delay the progression of renal damage in diabetes mellitus. Whatever the drug used to treat hypertension, the majority of the authors conclude that blood pressure levels should be maintained below 130/85 mmHg in diabetic patients. While it is well established that uncontrolled diabetes underlies the development of diabetic nephropathy, newer evidence suggests that genetically determined susceptibility to hyperglycemia-caused glomerular injury is also necessary. More information on this issue will help to design new therapeutical approaches to treat hypertension and renal complications in type 2 diabetes.
 ...
PMID:Hypertension and renal complications in type 2 diabetes. 1622 1

Cardiomyopathy is a major cause of mortality for both type 1 and 2 diabetic patients. However, experimental analysis of diabetic cardiomyopathy has focused on type 1 diabetes and there are few reports on cardiomyocyte dysfunction in the widely used type 2 diabetic model, db/db. In the current study, we assessed function in isolated ventricular myocytes from type 1 diabetic OVE26 mice and from type 2 diabetic db/db mice. When compared with their respective control strains, both diabetic models showed significant impairment in contractility, as assessed by percent peak shortening, maximal rate of contraction, and maximal rate of relaxation. The calcium decay rate was also significantly reduced in both types of diabetes, but the decrement was much greater in OVE26 myocytes, approx 50% vs only 20% in db/db myocytes. To understand the basis for slow calcium decay in diabetic myocytes and to understand the molecular basis for the quantitative difference between calcium decay in OVE26 and db/db myocytes, we measured cardiac content of the SERCA2a calcium pump. SERCA2a was significantly decreased in OVE26 diabetic myocytes but not reduced at all in db/db myocytes. The reduction of SERCA2a in OVE26 myocytes was completely prevented by overexpression of the antioxidant protein metallothionein, confirming that oxidative stress is an important component of diabetic cardiomyopathy. The current results demonstrate that though contractility is impaired in individual myocytes of db/db hearts and deficits are similar to what is seen in a severe model of type 1 diabetes, impairment in calcium reuptake is less severe, probably as a result of maintenance of normal levels of SERCA2a.
 ...
PMID:Cardiomyocyte dysfunction in models of type 1 and type 2 diabetes. 1624 73

Type 1 and type 2 diabetes are characterized by progressive beta-cell failure. Apoptosis is probably the main form of beta-cell death in both forms of the disease. It has been suggested that the mechanisms leading to nutrient- and cytokine-induced beta-cell death in type 2 and type 1 diabetes, respectively, share the activation of a final common pathway involving interleukin (IL)-1beta, nuclear factor (NF)-kappaB, and Fas. We review herein the similarities and differences between the mechanisms of beta-cell death in type 1 and type 2 diabetes. In the insulitis lesion in type 1 diabetes, invading immune cells produce cytokines, such as IL-1beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. IL-1beta and/or TNF-alpha plus IFN-gamma induce beta-cell apoptosis via the activation of beta-cell gene networks under the control of the transcription factors NF-kappaB and STAT-1. NF-kappaB activation leads to production of nitric oxide (NO) and chemokines and depletion of endoplasmic reticulum (ER) calcium. The execution of beta-cell death occurs through activation of mitogen-activated protein kinases, via triggering of ER stress and by the release of mitochondrial death signals. Chronic exposure to elevated levels of glucose and free fatty acids (FFAs) causes beta-cell dysfunction and may induce beta-cell apoptosis in type 2 diabetes. Exposure to high glucose has dual effects, triggering initially "glucose hypersensitization" and later apoptosis, via different mechanisms. High glucose, however, does not induce or activate IL-1beta, NF-kappaB, or inducible nitric oxide synthase in rat or human beta-cells in vitro or in vivo in Psammomys obesus. FFAs may cause beta-cell apoptosis via ER stress, which is NF-kappaB and NO independent. Thus, cytokines and nutrients trigger beta-cell death by fundamentally different mechanisms, namely an NF-kappaB-dependent mechanism that culminates in caspase-3 activation for cytokines and an NF-kappaB-independent mechanism for nutrients. This argues against a unifying hypothesis for the mechanisms of beta-cell death in type 1 and type 2 diabetes and suggests that different approaches will be required to prevent beta-cell death in type 1 and type 2 diabetes.
 ...
PMID:Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. 1630 47

Milk from dairy cows has long provided a high quality source of protein and selected micronutrients such as calcium to most populations. Recently, a relationship between disease risk and consumption of a specific bovine ss-casein fraction either A1 or A2 genetic variants has been identified. Populations, which consume milk containing high levels of ss-casein A2 variant, have a lower incidence of cardiovascular disease and type 1 diabetes. Furthermore, consumption of milk with the A2 variant may be associated with less severe symptoms of autism and schizophrenia. The mechanism of action focuses on ss-casein A1 and related forms preferentially that are able to produce a bioactive opioid peptide, ss-casomorphin-7 (ss-CM-7) during digestion. Infants may absorb ss-CM-7 due to an immature gastrointestinal tract. Adults, on the other hand, appear to reap the biological activity locally on the intestinal brush boarder. ss-CM-7 can potentially affect numerous opioid receptors in the nervous, endocrine, and immune systems. Whether there is a definite health benefit to milk containing the A2 genetic variant is unknown and requires further investigation.
 ...
PMID:Health implications of milk containing beta-casein with the A2 genetic variant. 1640 84

The in vitro availability studies of glibenclamide in presence of commonly used antacids are present in this paper. Glibenclamide is used for the treatment of Non-Insulin dependent diabetes mellitus. It is a sulfonylurea derivative. Antacids are prescribed to encounter gastric acidity etc. These studies were carried out in simulated gastric juice and in buffer of pH 7.4 at 37 and 48 degrees C. Aluminum hydroxide, aluminum trisilicate, magnesium oxide, magnesium trisilicate, sodium bicarbonate, calcium carbonate, magaldrate and simethicone (2,4-dimethoxypolysiloxane) antacids were used in these studies. It has been observed that in case of magnesium oxide, magnesium trisilicate and sodium bicarbonate, availability of glibenclamide was enhanced while in rest of the antacids retarded the availability of glibenclamide.
 ...
PMID:In vitro availability of glibenclamide in presence of antacids. 1641 96


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>