Effect of 1,25 dihydroxyvitamin D3 on isolated islets from vitamin D3-deprived rats

Billaudel, B.; Faure, A; Sutter, B. C. J.

doi:10.1152/ajpendo.1990.258.4.e643

Cited by 20 publications

(30 citation statements)

References 19 publications

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“…Indeed, in previous studies we found that the beneficial influence of 1,25(OH) 2 D 3 on insulin release is only seen when the cells are stimulated and not in basal conditions. It is observable only after 6 h of induction (Billaudel et al 1990) and it cannot occur in the presence of cycloheximide, a transcriptional inhibitor (Bourlon et al 1999). Moreover, in this recent study, we show that the total islets proteins is not statistically modified by vitamin D 3 deficiency or by 1,25(OH) 2 D 3 , whereas the amount of newly synthesised labelled proteins during a glucose stimulation exhibits some variation.…”

Section: Discussionmentioning

confidence: 46%

“…12 M as a control as this dose is not considered to be biologically active (Billaudel et al 1990). Previous work has shown an identical level of islets insulin release for such 10 12 M controls and other controls using the vehicle alone (Bourlon et al 1999).…”

Section: Animals and Isolation Of Islets Of Langerhansmentioning

confidence: 99%

“…The genomic actions of this steroid on cells of the endocrine pancreas have been emphasised (Norman et al 1982. 1,25(OH) 2 D 3 activates the cell insulin response to glucose in vivo after a delay of 3 to 20 h (Ishida et al 1983, Kadowaki & Norman 1985, Cade & Norman 1987, Ozono et al 1990), or after 6 h in vitro (Billaudel et al 1990), via an improvement of calcium handling occurring after a 4-h delay (Billaudel et al 1990), increasing both Ca 2+ entry by voltagedependent channels and Ca 2+ mobilisation from Ca 2+ stores (Billaudel et al 1993). However, these beneficial influences of 1,25(OH) 2 D 3 can be observed more rapidly (within 45 min) when the protein kinase C (PKC) pathway of the cell is stimulated by acetylcholine (Billaudel et al 1995) or by PKC activators such as phorbol esters 12-O-tetradecanoyl-phorbol-13-acetate (TPA) .…”

Section: Introductionmentioning

confidence: 99%

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The de novo synthesis of numerous proteins is decreased during vitamin D3 deficiency and is gradually restored by 1, 25-dihydroxyvitamin D3 repletion in the islets of langerhans of rats

Bourlon¹,

Faure-Dussert²,

Billaudel³

1999

Journal of Endocrinology

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Since both the release and de novo biosynthesis of insulin are severely decreased by vitamin D 3 deficiency and improved by 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) repletion following a 6-h delay in the rat, the present experiments investigated the effects of vitamin D 3 deficiency on the biosynthesis of heavier molecular weight proteins using electrophoretic separation. Gel protein staining by Coomassie blue showed very different profiles for islets protein production from 4-week vitamin D 3 -deficient rats compared with normal islets. The pattern was characterised by a decrease in high molecular weight proteins, concomitantly accompanied by an increase in low molecular weight proteins. This tendency was partially reversed in vivo by 1,25(OH) 2 D 3 repletion treatment for 7 days and was evident after only 16 h of treatment.In parallel with these in vivo observations, which represent a static index of islets protein production, a kinetic study was performed in vitro by a double-labelling method allowing us to measure the de novo synthesis of proteins in islets during a strong 16·7 mM glucose stimulation. Comparison of 3 H and 14 C labelled samples was achieved via coelectrophoresis to avoid experimental artefacts. The study of the ratio of d.p.m.3 H/d.p.m. 14 C for each molecular weight protein in islets stimulated by 16·7 mM glucose (versus basal 4·2 mM glucose) showed an increase in the height of certain peaks: 150, 130 and 8·5 kDa.Under the same conditions, islets from 4-week vitamin D 3 -deficient rats (versus normal islets) presented a large deficit of numerous newly synthesised proteins and particularly those implicated in the response to glucose stimulation. In vitro repletion of 1,25(OH) 2 D 3 tended to reverse, at least in part, the deleterious effect of vitamin D 3 deficiency on the de novo protein synthesis of islets but these effects were gradual. Indeed, there was no detectable effect at 2 h incubation, but 1,25(OH) 2 D 3 increased the 60 to 65 kDa, 55 kDa, and 9 to 8 kDa molecular mass proteins at 4 h, and increased the level of most newly synthesised proteins at 6 h. These data support the hypothesis of a beneficial genomic influence of 1,25(OH) 2 D 3 that occurs progressively within the islets of Langerhans and which may prepare the cells for an enhanced response to glucose stimulation.

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Section: Discussionmentioning

confidence: 46%

Section: Animals and Isolation Of Islets Of Langerhansmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The de novo synthesis of numerous proteins is decreased during vitamin D3 deficiency and is gradually restored by 1, 25-dihydroxyvitamin D3 repletion in the islets of langerhans of rats

Bourlon¹,

Faure-Dussert²,

Billaudel³

1999

Journal of Endocrinology

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“…In animal models, vitamin D deficiency impairs insulin synthesis (21,22), possibly via a reduced intracellular calcium concentration (23). The final statistical models presented in our study were adjusted for indices of glycemic control, such as glycated hemoglobin, fasting glucose, and insulin, so b-cell dysfunction and abnormal glucose homoeostasis may partly explain the increased risk of microvascular, but not macrovascular, disease, with decreasing blood concentrations of 25OH-D.…”

Section: Discussionmentioning

confidence: 99%

Serum 25-Hydroxyvitamin D: A Predictor of Macrovascular and Microvascular Complications in Patients With Type 2 Diabetes

et al. 2014

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OBJECTIVEPeople with diabetes frequently develop vascular disease. We investigated the relationship between blood 25-hydroxyvitamin D (25OH-D) concentration and vascular disease risk in type 2 diabetes. RESEARCH DESIGN AND METHODSThe relationships between blood 25OH-D concentration at baseline and the incidence of macrovascular (including myocardial infarction and stroke) and microvascular (retinopathy, nephropathy, neuropathy, and amputation) disease were analyzed with Cox proportional hazards models and logistic regression in an observational study of patients in the 5-year Fenofibrate Intervention and Event Lowering in Diabetes trial. RESULTSA total of 50% of the patients had low vitamin D concentrations, as indicated by median blood 25OH-D concentration of 49 nmol/L. These patients with a blood 25OH-D concentration <50 nmol/L had a higher cumulative incidence of macrovascular and microvascular events than those with levels ‡50 nmol/L. Multivariate analysis, stratified by treatment and adjusted for relevant confounders, identified blood 25OH-D concentration as an independent predictor of macrovascular events. A 50 nmol/L difference in blood 25OH-D concentration was associated with a 23% (P = 0.007) change in risk of macrovascular complications during the study, and further adjustments for seasonality, hs-CRP, and physical activity level had little impact. The unadjusted risk of microvascular complications was 18% (P = 0.006) higher during the study, though the excess risk declined to 11-14% and lost significance with adjustment for HbA 1c , seasonality, or physical activity. CONCLUSIONSLow blood 25OH-D concentrations are associated with an increased risk of macrovascular and microvascular disease events in type 2 diabetes. However, a causal link remains to be demonstrated.Diabetes is among the leading causes of death and affects 347 million people worldwide. The World Health Organization expects a 50% increase in deaths from diabetes over the next 10 years, and by 2030, diabetes is projected to be the seventh leading cause of death (1). Most major complications involve large vessel (macrovascular) or small vessel (microvascular) disease.

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“…1,25(OH) 2 D 3 has multiple effects that can explain this protection against diabetes. First, there is the effect on the b cell: 1,25(OH) 2 D 3 influences b cell calcium metabolism and eventually insulin secretion [33][34][35], and it has been described that 1,25(OH) 2 D 3 protects against IL-1b-induced b cell dysfunction [36]. Second, 1,25(OH) 2 Apoptosis is expressed as percentage TUNEL-positive cells (b).…”

Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 restores sensitivity to cyclophosphamide-induced apoptosis in non-obese diabetic (NOD) mice and protects against diabetes

Casteels¹,

Waer

Bouillon³

et al. 1998

Clinical and Experimental Immunology

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SUMMARYThe activated form of vitamin D, 1,25(OH) 2 D 3 , and its analogues can prevent type I diabetes in NOD mice. Protection is achieved without signs of systemic immunosuppression and is associated with a restoration of the defective immune regulator system of the NOD mice. The aim of the present study was to investigate whether this restoration of regulator cell function is the only mechanism in the prevention of diabetes by 1,25(OH) 2 D 3 . We tested therefore if 1,25(OH) 2 D 3 could prevent cyclophosphamideinduced diabetes, since diabetes occurring after cyclophosphamide injection is believed to be due to an elimination of suppresser cells. NOD mice treated with 1,25(OH) 2 D 3 (5 mg/kg every 2 days) from the time of weaning were clearly protected against diabetes induced by cyclophosphamide (200 mg/kg body wt at 70 days old) (2/12 (17%) versus 36/53 (68%) in control mice, P < 0·005). By co-transfer experiments it was demonstrated that cyclophosphamide had indeed eliminated the suppresser cells present in 1,25(OH) 2 D 3 -treated mice. Since cyclophosphamide injection did not break the protection offered by 1,25(OH) 2 D 3 , it was clear that diabetogenic effector cells were affected by 1,25(OH) 2 D 3 treatment as well. This was confirmed by the finding that splenocytes from 1,25(OH) 2 D 3 -treated mice were less capable of transferring diabetes in young, irradiated NOD mice, and by the demonstration of lower Th1 cytokine levels in the pancreases of 1,25(OH) 2 D 3 -treated, cyclophosphamide-injected mice. This better elimination of effector cells in 1,25(OH) 2 D 3 -treated mice could be explained by a restoration of the sensitivity to cyclophosphamide-induced apoptosis in both thymocytes and splenocytes, in normally apoptosis-resistant NOD mice. Altogether, these data indicate that the protection against diabetes offered by 1,25(OH) 2 D 3 may be independent of the presence of suppresser cells, and may involve increased apoptosis of Th1 autoimmune effector cells.

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Effect of 1,25 dihydroxyvitamin D3 on isolated islets from vitamin D3-deprived rats

Cited by 20 publications

References 19 publications

The de novo synthesis of numerous proteins is decreased during vitamin D3 deficiency and is gradually restored by 1, 25-dihydroxyvitamin D3 repletion in the islets of langerhans of rats

The de novo synthesis of numerous proteins is decreased during vitamin D3 deficiency and is gradually restored by 1, 25-dihydroxyvitamin D3 repletion in the islets of langerhans of rats

Serum 25-Hydroxyvitamin D: A Predictor of Macrovascular and Microvascular Complications in Patients With Type 2 Diabetes

1,25-Dihydroxyvitamin D3 restores sensitivity to cyclophosphamide-induced apoptosis in non-obese diabetic (NOD) mice and protects against diabetes

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