Biomedical subjects

Eduard Montanya

Publications and source records attributed to Eduard Montanya.

9 recordsLinked to original sources

PubMed2026

Association of Post-Oral Glucose Tolerance Test Hypoglycaemia With Clinical Features, Incident Diabetes and Mortality in the Di@bet.es Cohort.

AIMS: To investigate the association of post-oral glucose tolerance test (OGTT) hypoglycaemia with clinical features, incident diabetes and mortality. MATERIALS AND METHODS: This population-based cohort study included 2924 adults (median age 49 years, 1680 women) without known diabetes who underwent a 75-g OGTT as part of the Di@bet.es Study. Metabolic, demographic and lifestyle variables were collected. Serum glucose and insulin concentrations at 0, 30 and 120 min during the OGTT were obtained, allowing insulin resistance estimation using the HOMA-IR and the Matsuda Index. Participants were grouped according to serum glucose at 120 min: < 70 mg/dL (post-OGTT hypoglycaemia), 70 to < 140 mg/dL (normal result), 140 to < 200 mg/dL, and ≥ 200 mg/dL. The incidence of diabetes (median follow-up, 7.5 years) and mortality (median follow-up, 14.5 years) were assessed. RESULTS: Participants with post-OGTT hypoglycaemia (n = 327, 11.1%) were younger, leaner, less insulin resistant and more frequently active smokers. Despite having the lowest serum glucose at 0, 30 and 120 min, and the lowest serum insulin at 0 and 120 min, these participants tended to have the highest serum insulin concentrations at 30 min. Participants with post-OGTT hypoglycaemia had the lowest incidence of diabetes and mortality, although these associations were attenuated after adjusting for confounders (such as age, sex, body mass index and physical activity) and when compared specifically with the normal result group. CONCLUSIONS: Post-OGTT hypoglycaemia is more frequent in smokers, younger individuals, and those with a favourable metabolic profile. Post-OGTT hypoglycaemia acts as a marker of protection for incident diabetes and mortality. Preserved early insulin secretion together with good insulin sensitivity could explain post-OGTT hypoglycaemia.

Humans↗

PubMed2024

Implications of noncoding regulatory functions in the development of insulinomas.

Insulinomas are rare neuroendocrine tumors arising from pancreatic β cells, characterized by aberrant proliferation and altered insulin secretion, leading to glucose homeostasis failure. With the aim of uncovering the role of noncoding regulatory regions and their aberrations in the development of these tumors, we coupled epigenetic and transcriptome profiling with whole-genome sequencing. As a result, we unraveled somatic mutations associated with changes in regulatory functions. Critically, these regions impact insulin secretion, tumor development, and epigenetic modifying genes, including polycomb complex components. Chromatin remodeling is apparent in insulinoma-selective domains shared across patients, containing a specific set of regulatory sequences dominated by the SOX17 binding motif. Moreover, many of these regions are H3K27me3 repressed in β cells, suggesting that tumoral transition involves derepression of polycomb-targeted domains. Our work provides a compendium of aberrant cis-regulatory elements affecting the function and fate of β cells in their progression to insulinomas and a framework to identify coding and noncoding driver mutations.

Humans↗

PubMed2007

Interleukin-1beta and inducible form of nitric oxide synthase expression in early syngeneic islet transplantation.

Islets are particularly vulnerable in the initial days after transplantation when cell death results in the loss of more than half of the transplanted islet tissue. To determine whether a non-specific inflammation at the grafted site mediated by the local expression of inflammatory cytokines could play a role on the initial damage to transplanted islets, we studied the expressions of interleukin-1beta (IL-1beta) and inducible form of nitric oxide synthase (iNOS) after syngeneic islet transplantation. Insulin-treated streptozotocin-diabetic Lewis rats were syngeneically transplanted with 500 islets. Grafts were harvested 1, 3, or 7 days after transplantation, and the expressions of IL-1beta and iNOS genes were determined by RT-PCR. IL-1beta and iNOS mRNAs were detected in islets immediately after isolation, and were upregulated after transplantation. IL-1beta mRNA was ninefold increased on day 1, was still sevenfold increased on day 3 after transplantation, and declined towards pretransplantation levels on day 7. iNOS mRNA showed a similar pattern of expression to that of IL-1beta: on days 1 and 3 after transplantation it was 14-and 4-fold higher respectively than in freshly isolated islets. In addition, IL-1beta and iNOS were identified in islet grafts and found to be produced mainly by CD68-positive macrophages. A low number of IL-1beta- and iNOS-positive but CD68-negative cells were also identified suggesting that other cell types, in addition to macrophages, were involved in the expression of IL-1beta and NO production in islet grafts. The finding of increased IL-1beta and iNOS gene expressions in the initial days after islet transplantation and the presence of IL-beta and iNOS proteins in the graft confirmed the presence of an early non-specific inflammatory response after islet transplantation. Overall, the data suggest that IL-1beta plays a role in the extensive beta-cell death found in the initial days after islet transplantation.

Animals↗

PubMed2005

Selection of a suitable internal control gene for expression studies in pancreatic islet grafts.

The use of real-time reverse transcription polymerase chain reaction to compare gene expression in different tissues and conditions requires normalization to an internal control that must be expressed at a constant level. Although a previous validation step is required to confirm that an internal control is appropriate, no comparison of frequently used "housekeeping" genes is available for islet grafts. We have investigated the effect of transplantation and metabolic environment on the expression of 18S, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-actin, and cyclophilin A genes in pancreatic islets. The expression of these genes was determined on days 1, 3, and 7 after transplantation into normoglycemic or hyperglycemic rats and in isolated islets. Only 18S gene expression remained stable in all studied conditions, indicating that it is the best internal control for gene expression analysis in islet grafts. The significant variation found in other housekeeping genes, particularly GAPDH and beta-actin, question their use as internal controls in islet grafts.

Actins↗

PubMed2005

Renoprotective effect of diltiazem in hypertensive type 2 diabetic patients with persistent microalbuminuria despite ACE inhibitor treatment.

The aim of the study was to evaluate the effects of the non-dihydropyridine calcium antagonist (NDCA) diltiazem on the development of urinary albumin excretion (UAE) in type 2 hypertensive diabetic patients with persistent microalbuminuria despite ACE inhibitor treatment. Thirty-six type 2 diabetic hypertensive patients with microalbuminuria persisting after at least 1 year of treatment with ACE inhibitors were randomized to receive captopril (n=22) or combined therapy with captopril and 120 mg diltiazem (n=14) for 2 years. Captopril dose was individualized according to blood pressure. Changes in UAE, blood pressure, and metabolic control were monitored to analyze the influence of the addition of diltiazem on progression of diabetic nephropathy. In patients treated with captopril and diltiazem, absolute UAE did not change during the study (baseline: 101 mg/24 h, range 39-298; 2 years after randomization: 74 mg/24 h, range 12-665). In contrast, UAE increased in patients treated with captopril monotherapy (baseline: 118 mg/24 h, range 32-282; 2 years after randomization: 164 mg/24 h, range 15-1161, p<0.05). In addition, fewer patients in the captopril/diltiazem group progressed to macroalbuminuria (eight patients in captopril group and one in captopril/diltiazem group, p<0.05). The beneficial effects of the addition of diltiazem were independent of blood pressure and metabolic control. We suggest that the combination of ACE inhibitors and NDCA should be considered in type 2 microalbuminuric patients at high risk for progression to established diabetic nephropathy.

Albuminuria↗

PubMed2005

Short-term culture with the caspase inhibitor z-VAD.fmk reduces beta cell apoptosis in transplanted islets and improves the metabolic outcome of the graft.

In the initial days after transplantation islets are particularly vulnerable and show increased apoptosis and necrosis. We have studied the effects of caspase inhibition on this early beta cell death in syngeneically transplanted islets. Streptozotocin-diabetic C57BL/6 mice were transplanted with 150 syngeneic islets, an insufficient mass to restore normoglycemia, preincubated with or without the pan-caspase inhibitor z-VAD. fmk 2 h before transplantation. Beta cell apoptosis was increased in control islets on day 3 after transplantation (0.28 +/- 0.02%) compared with freshly isolated islets (0.08 +/- 0.02%, p < 0.001), and was partially reduced in transplanted islets preincubated with z-VAD.fmk 200 microM (0.14 +/- 0.02%, p = 0.003) or with z-VAD.fmk 500 microM (0.17 +/- 0.01%, p = 0.012), but not with a lower z-VAD.fmk (100 microM) concentration. Diabetic mice transplanted with islets preincubated with z-VAD.fmk 500 microM showed an improved metabolic evolution compared with control and z-VAD.fmk 200 microM groups. The z-VAD.fmk 500 microM group showed an overall lower blood glucose after transplantation (p = 0.02), and at the end of the study blood glucose values were reduced compared with transplantation day (15.7 +/- 3.6 vs. 32.5 +/- 0.5 mmol/L, p = 0.001). In contrast, blood glucose was not significantly changed in control and z-VAD.fmk 200 microM groups. Four weeks after transplantation beta cell mass was higher in z-VAD.fmk 500 microM group (0.15 +/- 0.02 mg) than in the control group (0.10 +/- 0.02 mg) (p = 0.043). In summary, the treatment of freshly isolated islets with the caspase inhibitor z-VAD.fmk reduced the subsequent apoptosis of the islets once they were transplanted and improved the outcome of the graft.

Amino Acid Chloromethyl Ketones↗

PubMed2004

Islet- and stem-cell-based tissue engineering in diabetes.

New sources of insulin-producing cells are needed to overcome the limited availability of islet tissue for transplantation to diabetic patients. The engineering of murine or human transformed beta-cell lines and of non beta-cells has progressed slowly in recent years, while significant achievements have been claimed in the differentiation of insulin-producing cells from embryonic and adult stem cells. Some of the results have been questioned, however, and the generated cells lack many characteristics of differentiated beta-cells. A much better understanding of the processes that govern the expansion and differentiation of stem cells is needed.

Animals↗

PubMed2002

A relapsed non-Hodgkin lymphoma presenting as panhypopituitarism successfully treated by chemotherapy.

We report a case of relapsed large B-cell non-Hodgkin lymphoma (NHL) affecting the anterior pituitary. The NHL relapsed after three years in complete remission. The patient was a 72-year-old woman who presented fever, weakness, hyponatremia, and hypotension. The levels of thyroid-stimulating hormone and gonadotropins were very low and magnetic resonance imaging showed infiltration of the pituitary gland and stalk. After controlling the hormonal deficiencies with substitution using hydroxycortisone and levothyroxin, the patient was treated with combination chemotherapy using cyclophosphamide, vincristine, mitoxantrone, etoposide, and bleomycin (VNCOP-B regimen), achieving a complete regression of the pituitary mass and partial recovery of the endocrine function. Lymphoproliferative disorders affecting the anterior pituitary are exceedingly rare, with only six cases in immunocompetent adults reported in the literature. To our knowledge this is the first report of a relapsed NHL presenting by hypopituitarism.

Aged↗

PubMed2002

Beta-cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia.

We studied the effects of hyperglycemia on beta-cell death and mass in syngeneically transplanted islets. Six groups of STZ-induced diabetic C57BL/6 mice were transplanted with 100 syngeneic islets, an insufficient beta-cell mass to restore normoglycemia. Groups 1, 2, and 3 remained hyperglycemic throughout the study. Groups 4, 5, and 6 were treated with insulin from day 7 before transplantation to day 10 after transplantation. After insulin discontinuation, group 6 mice achieved definitive normoglycemia. Grafts were harvested at 3 (groups 1 and 4), 10 (groups 2 and 5), and 30 (groups 3 and 6) days after transplantation. On day 3, the initially transplanted beta-cell mass (0.13 +/- 0.01 mg) was dramatically and similarly reduced in the hyperglycemic and insulin-treated groups (group 1: 0.048 +/- 0.002 mg; group 4: 0.046 +/- 0.007 mg; P < 0.001). Extensive islet necrosis (group 1: 30.7%; group 4: 26.8%) and increased beta-cell apoptosis (group 1: 0.30 +/- 0.05%; group 4: 0.42 +/- 0.07%) were found. On day 10, apoptosis remained increased in both hyperglycemic and insulin-treated mice (group 2: 0.44 +/- 0.09%; group 5: 0.48 +/- 0.08%) compared with normal pancreas (0.04 +/- 0.03%; P < 0.001). In contrast, on day 30, beta-cell apoptosis was increased in grafts exposed to sustained hyperglycemia (group 3: 0.37 +/- 0.03%) but not in normoglycemic mice (group 6: 0.12 +/- 0.02%); beta-cell mass was selectively reduced in islets exposed to hyperglycemia (group 3: 0.046 +/- 0.02 mg; group 6: 0.102 +/- 0.009 mg; P < 0.01). In summary, even in optimal conditions, approximately 60% of transplanted islet tissue was lost 3 days after syngeneic transplantation, and both apoptosis and necrosis contributed to beta-cell death. Increased apoptosis and reduced beta-cell mass were also found in islets exposed to chronic hyperglycemia, suggesting that sustained hyperglycemia increased apoptosis in transplanted beta-cells.

Animals↗