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D Mauricio

Publications and source records attributed to D Mauricio.

32 records · Page 2Linked to original sources
PubMed1997

Dexamethasone prevents interleukin-1beta-mediated inhibition of rat islet insulin secretion without decreasing nitric oxide production.

The deleterious effects of interleukin 1 (IL-1) on insulin-producing beta-cells are partly mediated by the generation of the free radical nitric oxide (NO). We aimed to assess the effect of several steroidal hormones on IL-1beta-induced inhibition of rat islet insulin secretion in vitro, and their possible regulatory effects on NO production. Incubation of newborn rat islets for 24 h in the presence of 150 pg/ml IL-1beta revealed that dexamethasone dose-dependently attenuated the inhibitory effect of IL-1beta on insulin release in response to a 2-h glucose challenge. Physiological and supraphysiological concentrations of testosterone, 17beta-estradiol, progesterone, 1,25-dihydroxyvitamin-D3 and vitamin D analogues (KH1060 and MC1288) were ineffective. Dexamethasone (1 microM) increased the production of NO in IL-1beta-treated rat islets, as measured by the concentration of nitrite in the media. However, 1-5 microM dexamethasone inhibited IL-1beta-induced NO production by RIN cells. Dexamethasone (1 microM) did not affect the inhibitory action of the NO donor S-nitroso penicillamine (500 microM) on rat islet insulin secretion. We conclude that dexamethasone partially protects against IL-1beta-induced inhibition of rat islet insulin secretion, an effect which is not mediated through modulation of the NO pathway.

Animals↗
PubMed1997

Lipoprotein compositional abnormalities in type I diabetes: effect of improved glycaemic control.

Major lipoprotein mass and composition were assessed in 45 subjects with insulin dependent diabetes mellitus (IDDM), before and after 2 months of intensive insulin therapy (IIT) and in 40 healthy control subjects. As compared to the control group, diabetic subjects at baseline had higher low density lipoprotein (LDL) and lower high density lipoprotein (HDL) masses. Expressing each lipoprotein constituent as a percent of total lipoprotein mass, very low density lipoprotein (VLDL) of diabetic patients was enriched in cholesterol and phospholipid and depleted in triglyceride and protein; IDL had higher triglyceride and phospholipid and lower cholesterol and protein proportion; LDL was depleted in protein and enriched in triglyceride; HDL was depleted in protein and enriched in triglyceride, cholesterol and phospholipid. After 2 months of IIT, HbA1c fell from 10.3 +/- 2 to 7.5 +/- 2% (P < 0.0001) and so did VLDL mass, which was lower than in control subjects. In addition, LDL and HDL masses, as well as triglyceride and cholesterol proportion in IDL particles normalized. The other compositional abnormalities improved without complete normalization. Thus, intensive insulin therapy in IDDM subjects brought quantitative lipoprotein alterations to normal even subnormal range, while most of the composition abnormalities improved without reaching complete normalization.

Adolescent↗
PubMed1997

Insulin antibody response to a short course of human insulin therapy in women with gestational diabetes.

OBJECTIVE: To assess the insulin antibody (IA) response to human insulin (HI) therapy in women with gestational diabetes. RESEARCH DESIGN AND METHODS: IAs were measured by a competitive radiobinding assay in 50 women with gestational diabetes before and during treatment with HI and after delivery. At delivery, 15 maternal-cord blood sample pairs were analyzed for IA. As a reference, we searched for IA in 25 new-onset type I diabetic patients, before and at 3, 6, and 12 months after insulin therapy. RESULTS: Insulin autoantibodies (IAAs) were detected in 1 of 50 women with gestational diabetes and 4 of 16 type I diabetic patients (P < 0.05). At the end of pregnancy after 9.3 +/- 6.8 weeks on insulin therapy, 22 of 50 (44%) women with gestational diabetes became IA+ and 4 additional women were found to be positive 2 months postpartum. After 3 months on insulin, type I diabetic patients showed a higher rate of IA positivity (92%, P < 0.001). IA titers at the end of pregnancy were associated with the cumulative insulin dose (r = 0.29, P < 0.05). Postpartum, IA disappeared slowly in most IA+ women, but two women still showed IA 2 years after delivery Titers in cord blood were strongly related to those in maternal blood (r = 0.74, P < 0.01). The rate of adverse fetal outcome did not differ in IA and IA- mothers (27 vs. 40%, NS). CONCLUSIONS: HI is immunogenic, and a short course of HI therapy induces IA in approximately 50% of women with gestational diabetes and 92% of type I diabetic patients. In women with gestational diabetes, insulin dose is slightly associated with IA titers. These IAs apparently cross the placenta. Fetal outcome does not differ according to the maternal IA status, and IAs disappear gradually after delivery but may remain positive for 2 years after delivery.

Adolescent↗
PubMed1996

Interleukin-1 beta-induced nitric oxide production from isolated rat islets is modulated by D-glucose and 3-isobutyl-1-methyl xanthine.

Interleukin-1 beta has been proposed to cause selective beta-cell destruction via the induction of nitric oxide synthesis. The cytotoxic effect of interleukin-1 beta is modulated by the concentration of D-glucose in the medium. The aim of this study was to investigate if D-glucose-mediated modulation of interleukin-1 beta effects on insulin release from isolated rat islets was related to modulation of nitric oxide production. Further, we wished to investigate the effects of agents increasing the intracellular concentration of cAMP on interleukin-1 beta-induced nitrite production. We demonstrated that D-glucose potentiated interleukin-1 beta-induced nitrite production in rat islets without affecting the mRNA level of the inducible nitric oxide synthase. This effect was dissociated from interleukin-1 beta action on insulin release, since a relative protection against interleukin-1 beta effects on acute insulin release was found at high (28 mmol/l) concentrations of D-glucose, and blocking nitrite production by the L-arginine analog aminoguanidine, which selectively inhibits the cytokine-inducible nitric oxide synthase, did not result in protection against the inhibitory action of interleukin-1 beta. Neither L-glucose nor the secretagogues L-leucine, tolbutamide and 3-isobutyl-1-methyl xanthine shared the potentiating effect of D-glucose. The phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine reduced interleukin-1 beta-induced nitrite production at 3.3 mmol/l D-glucose, an effect that could be reproduced by the cAMP analog dibutyryl cAMP. Addition of 3-isobutyl-1-methyl xanthine resulted in a threefold reduction in the mRNA level of interleukin-1 beta-induced inducible nitric oxide synthase. We conclude that interleukin-1 beta-induced islet nitric oxide synthesis is augmented by D-glucose, but not by non-substrate secretagogues, and that secretagogues that elevate cAMP inhibit islet nitric oxide production.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Strain-dependent differences in sensitivity of rat beta-cells to interleukin 1 beta in vitro and in vivo: association with islet nitric oxide synthesis.

The aim of this study was to investigate whether strain-dependent differences in beta-cell sensitivity to interleukin (IL) 1 beta exist in vitro and in vivo and if so, whether these differences correlate to variations in IL-1 beta-induced islet inducible nitric oxide synthase (iNOS) mRNA expression and nitrite production in vitro and islet iNOS protein content in vivo. Isolated islets of Langerhans in vitro from Wistar-Kyoto/Møllegården (WK/Mol) rats were sensitive to the inhibitory effect of IL-1 beta on accumulated and acute insulin secretion, whereas islets from Brown Norway/Charles River (BN/CR) rats were resistant. Furthermore, IL-1 beta induced higher islet iNOS mRNA expression and nitric oxide production from WK/Mol islets compared with BN/CR islets. WK/Mol, WK/CR, BN/Mol, BN/CR, and Lewis-Scripps/Mol (LS/Mol) rats received one daily injection of recombinant human IL-1 beta (4.0 microg/kg) or vehicle for 5 days. All the strains investigated were susceptible to IL-1 beta-induced changes in body weight, food intake, temperature, and plasma glucagon and corticosterone. However, IL-1 beta induced hyperglycemia and impairment of beta-cell glucose responsiveness in WK/Mol and LS/Mol rats, but not in BN rats. Furthermore, IL-l beta-induced islet iNOS expression in vivo determined by immunostaining was greater in WK/Mol rats compared with WK/CR and BN/CR rats. No restriction fragment length polymorphisms, using 20 restriction enzymes, were identified in the iNOS gene in six rat strains including BioBreeding rats. In conclusion, the relative resistance of BN rat islets to IL-1 beta-induced inhibition of beta-cell function in vitro was associated with lower islet iNOS mRNA expression and nitrite production in this strain. Further, the resistance of BN rats to IL-1 beta-induced hyperglycemia was associated with a lower islet iNOS expression in vivo.

Animals↗
PubMed1996

Linomide increases plasma corticosterone in normal rats, but does not prevent the inhibitory action of IL-1 on beta-cells in vivo or ex vivo.

Recently, the synthetic immunomodulator Linomide (quinoline-3-carboxamide, LS 2616) was reported to prevent IDDM and insulitis in NOD mice. The mechanism for this protective effect is not known. The cytokine interleukin 1 (IL-1) may be a pathogenetic factor in the initial destruction of the beta-cells leading to IDDM. This study was undertaken to investigate the influence of Linomide on IL-1beta induced diabetogenic and hormonal changes in the rat in vivo, and on IL-1beta mediated synthesis of NO and inhibition of insulin secretion in isolated islets of Langerhans ex vivo. Normal male Wistar Kyoto rats received 4.0 microg/kg of recombinant human IL-1beta (rhIL-1beta) i.p. daily for 5 days with or without Linomide (8-9 mg/kg/day) in the drinking water. Litters of neonatal Wistar rats were pretreated for 3 days with injections of 10 mg/kg of Linomide i.p., and pancreatic islets of Langerhans were isolated for ex vivo studies. Linomide alone caused significant hypercorticosteronemia, hypoglucagonemia, lymphopenia and neutrophilia. Linomide had no effect on IL-1beta induced hyperglycemia, hyperglucagonemia, lymphopenia, neutrocytosis, or hypercorticosteronemia on day three and hypocorticosteronemia on day five. Further, Linomide did not prevent rhIL-1beta mediated reduction in insulin secretion or increase in NO synthesis ex vivo. In conclusion, Linomide does not seem to exert its protective effect on IDDM development via inhibition of interleukin 1 action on islet insulin release or NO production, but the increase in plasma corticosterone may contribute to the understanding of the immunomodulatory effects of Linomide.

Adjuvants, Immunologic↗
PubMed1995

Islet cell antibodies and beta-cell function in gestational diabetic women: comparison to first-degree relatives of type 1 (insulin-dependent) diabetic subjects.

In order to further characterize women with islet cell antibodies (ICA) at the diagnosis of gestational diabetes (GDM), we aimed to compare titres and persistence as well as B-cell function with those of ICA+ first-degree relatives of Type 1 (insulin-dependent) diabetic subjects. Titres at detection of ICA were compared between 69 women with GDM and 53 relatives. Persistence of ICA positivity was investigated in 33 ICA+ gestational diabetic women and 39 relatives (mean follow-up: 13 months). Assessment of the acute insulin response, through an intravenous glucose tolerance test (IVGTT), was carried out in 9 ICA+ women with previous GDM and normal oral glucose tolerance, and their results were compared to those of a control group (9 women) and a group of 12 adult ICA+ relatives. In comparison with first-degree relatives, women with GDM had a higher ICA prevalence, especially with titres of < 20 JDF, and a similar persistence at follow-up. Women with ICA at diagnosis of GDM and normal oral glucose tolerance after pregnancy showed a decreased insulin response to glucose as compared to the control group. Results of the IVGTT closely paralleled those from adult ICA+ relatives. It is concluded that ICA+ gestational diabetic women share with ICA+ first-degree relatives of Type 1 diabetic subjects metabolic and immunologic disturbances.

Adolescent↗
PubMedDate not supplied

Autoimmune gestational diabetes mellitus: a distinct clinical entity?

This review gives an update of the present knowledge on what is defined here as autoimmune gestational diabetes mellitus (GDM). Autoimmune phenomena associated with type 1 diabetes mellitus (DM) can be detected in a subgroup of women with GDM. Islet autoantibodies are present in sera from women with GDM with variable frequency. Distinct phenotypic and genotypic features may be recognised in this subset of women with GDM, which are representative of a distinct clinical entity. Furthermore, these women are at increased risk of developing type 1 DM after pregnancy. However, the eventual progression of the autoimmune destruction of beta-cells in these subjects may follow different time-course patterns thus leading to variable forms of presentation of autoimmune DM. As a high-risk group for type 1 diabetes, women with previous autoimmune GDM may be candidates for potential immune intervention strategies.

Autoantibodies↗
PubMedDate not supplied

Genetic, clinical, and biochemical analysis of unrelated Spanish families with multiple endocrine neoplasia type I.

OBJECTIVE: (1) To study seven unrelated Spanish families with multiple endocrine neoplasia type I (MEN I), describing clinical features and investigating the presence of germline mutations in the MEN1 gene, and (2) to establish reference values for pancreatic polypeptide and gastrin after a standardized test meal in a healthy control group, analyzing the usefulness of this test for detecting neuroendocrine gastroenteropancreatic tumors in subjects with MEN I. METHODS: Two or three generations of 7 kindreds with MEN I, consisting of a total of 39 individual family members, were investigated. Three of the families were subjected only to genetic analysis, and the other four families were also assessed clinically. A group of 23 healthy control subjects were also studied. RESULTS: Mutations in the MEN1 gene were found in six of the seven families studied. Of the 4 families studied clinically, 12 family members were genetically affected. In these study subjects, hyperparathyroidism, adrenal adenomas, neuroendocrine gastroenteropancreatic tumors, and pituitary adenomas developed in 100%, 50%, 16%, and 12%, respectively. All demonstrated pancreatic tumors were associated with abnormal results after a test meal, but 75% of them also showed high basal hormonal measurements. CONCLUSION: Analysis of the MEN1 gene decreases the total number of subjects who need to undergo repeated clinical and biochemical studies, but genetic mutations are not detected in all families with MEN I. Hyperparathyroidism is the most common manifestation of the syndrome, but the presence of adrenal adenomas has probably been underestimated. Ingestion of a standardized test meal for stimulation of gastrin and pancreatic polypeptide could be a complementary procedure for diagnosing gastroenteropancreatic tumors in selected patients with MEN I in whom basal gastrin and pancreatic polypeptide levels are normal.

Adenoma↗