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)

Recent studies have shown that plasma concentrations of vitamin A (retinol) and its carrier proteins, retinol-binding protein (RBP), and transthyretin (TTR), are decreased in human subjects with insulin-dependent (IDDM) but not with noninsulin dependent diabetes mellitus (NIDDM). Rats made diabetic with streptozotocin (STZ) have also been shown to have reduced levels of plasma vitamin A while its hepatic concentrations elevate. The circulatory vitamin A levels remained low while its hepatic concentrations were further elevated following supplementation of the vitamin. The reduced circulatory status of vitamin A in diabetic animals was not caused by its impaired intestinal absorption. Further experimental studies have pointed to the fact that IDDM is associated with a deficiency of vitamin A, which is secondary to an impaired transport mechanism of this vitamin from its hepatic storage to the target site, such as retina of the eyes. The diabetes-associated changes in vitamin A metabolism were reserved to normal by insulin treatment. The underlying cause for decreased metabolic availability in uncontrolled diabetes, is not clearly understood. It appears that the increased hepatic store of vitamin A is attributed to a decreased availability of its carrier proteins. Subnormal vitamin A status in poorly controlled diabetic subjects may not respond to vitamin A supplementation, rather it may increase its load in the liver leading to hepatoxicity. These results clearly suggest that there is need for further research identifying the importance of vitamin A in diabetes mellitus.
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PMID:Vitamin A homeostasis and diabetes mellitus. 999 May 81

Transthyretin (TTR) is a transport protein for thyroxine and, in association with retinol-binding protein, for retinol, mainly existing as a tetramer in vivo. We now demonstrate that TTR tetramer has a positive role in pancreatic beta-cell stimulus-secretion coupling. TTR promoted glucose-induced increases in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) and insulin release. This resulted from a direct effect on glucose-induced electrical activity and voltage-gated Ca(2+) channels. TTR also protected against beta-cell apoptosis. The concentration of TTR tetramer was decreased, whereas that of a monomeric form was increased in sera from patients with type 1 diabetes. The monomer was without effect on glucose-induced insulin release and apoptosis. Thus, TTR tetramer constitutes a component in normal beta-cell function. Conversion of TTR tetramer to monomer may be involved in the development of beta-cell failure/destruction in type 1 diabetes.
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PMID:Transthyretin constitutes a functional component in pancreatic beta-cell stimulus-secretion coupling. 1628 52

Type 1 diabetes is associated with the presence of inflammation, which in turn affects parameters used to assess the vitamin A status. In the present study, we evaluated the influence of inflammatory status on retinol, retinol-binding protein 4 (RBP4), and transthyretin (TTR) in children and adolescents with type 1 diabetes. A total of 40 children with type 1 diabetes (median age, 14.2 y; median BMI-SDS, 0.53; median diabetes duration, 5.8 y; median HbA1c, 7.3%) and 46 healthy subjects (median age, 12.8 y; median BMI-SDS, 0.34; median HbA1c 5.4%) were recruited. Serum levels of CRP were significantly elevated (p = 0.005) and retinol concentrations were significantly lower (p = 0.02) in children and adolescents with type 1 diabetes compared with healthy subjects. Serum RBP4 and TTR showed no differences between the groups. Healthy children with CRP levels above 0.6 mg/L had significant lower levels of retinol (p = 0.03). This was not observed in children with type 1 diabetes. The results suggest that, in contrast to healthy children, minor CRP elevation does not affect vitamin A transport complex in serum of children with type 1 diabetes.
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PMID:High-normal C-reactive protein levels do not affect the vitamin A transport complex in serum of children and adolescents with type 1 diabetes. 1795 46

Retinol-binding protein 4 (RBP4) is the principle carrier of retinol in the human plasma, which circulates as a complex with transthyretin (TTR), a homotetrameric thyroxine transport protein. Although this complex formation is thought to prevent glomerular filtration of RBP4, it also stabilizes the quaternary structure of TTR. Recent studies indicate elevated plasma levels of RBP4 in type 2 diabetes (T2D). In contrast, reduced RBP4 levels were observed in type 1 diabetes (T1D). Herein, we critically examine the probable mechanisms involved in the regulation of RBP4 and TTR levels during T2D and T1D. The available evidences point to the involvement of pancreatic factors in regulating the expression of both RBP4 and TTR. It appears that during T1D, TTR levels are reduced and it exists predominantly as a monomer that may interfere its interaction with RBP4 resulting in its loss through glomerular filtration. However, plasma TTR levels remain high under T2D conditions and thus reducing glomerular filtration of RBP4. Therefore, the plasma TTR levels appear to be an important determinant of plasma RBP4 levels in these two diabetic conditions.
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PMID:Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: the significance of transthyretin. 2312 25