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Biomedical subjects

R Gomis

Publications and source records attributed to R Gomis.

At least 109 records · Page 6Linked to original sources
PubMed1995

[Insulin treatment in diabetes mellitus type II: the usefulness of the breakfast test].

BACKGROUND: Insulin treatment in patients with type-II diabetes mellitus (DMII) is normally undertaken by clinical criteria. The aim of the present was to study the efficacy of a standard mixed meal (breakfast test) to predict the need for insulin therapy to thereby evaluate whether it is possible to obtain more objective criteria for the indication of insulin treatment. METHODS: Fifty-six patients with DMII were studied to evaluate the need for insulin therapy over a one-year period. Serum glucose and basal C peptide and their maximum values were determined in all the patients following stimulation with the breakfast test. Insulin treatment was initiated according to exclusively clinical criteria during admission. The patients were followed as out patients for a minimum of 3 months. Treatment at the end of follow up (insulin or no insulin) was evaluated and the results of the test were retrospectively analyzed. RESULTS: The basal C peptide (BCP) values were significantly lower in the individuals requiring insulin in comparison to those who did not require insulin (mean +/- SD 0.64 +/- 0.28 versus 1.18 +/- 0.41 nmol/l, p < 0.0001) similar to what was found with the stimulated maximum C peptide values (MCP) (1.48 +/- 0.77 versus 2.49 +/- 0.63 nmol/l, p < 0.0001). On considering a BCP of less than 0.9 nmol/l for the patients with insulin treatment the sensitivity of BCP was 83.6% and the specificity 78.9%. For a BCP value of less than 1.9 nmol/l sensitivity was 77.7% and specificity 78.9%. Using the values together, sensitivity was 66.6% and specificity 84.4%. CONCLUSIONS: The breakfast test is useful to indicate the need for insulin therapy in patients with type II diabetes mellitus but is not more useful than a determination of isolated basal C peptide.

Adult↗
PubMed1995

Apparent starvation-induced repression of pancreatic islet glucokinase.

Conflicting data were previously reported concerning the effect of starvation upon the glucokinase protein and glucokinase mRNA content of pancreatic islets. In the present study, conducted in fed rats and animals starved for 48 h, the catalytic activity of glucokinase in islet homogenates and the content of this enzyme in islets were both decreased by starvation to the same relative extent. These findings support the view that the altered metabolic and secretory response to D-glucose found in islets from starved rats may be attributable, in part at least, to an apparent repression of glucokinase.

Animals↗
PubMed1995

Anti-islet cell and anti-insulin antibody production by CD5+ and CD5- B lymphocytes in IDDM.

Although CD5 + B lymphocytes are mostly committed to the production of polyreactive natural autoantibodies, CD5 + B lymphocytes committed to the production of somatically mutated and monoreactive high-affinity IgM autoantibodies have been also shown. Increased proportions of CD5 + B lymphocytes in some autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM), have been noticed. The present study was undertaken to analyse the differences between CD5 + and CD5- B lymphocyte subsets for production of IDDM-related autoantibodies, i.e. anti-human insulin antibodies (IA) and anti-human islet cell antibodies (ICA). For this purpose, Epstein-Barr Virus (EBV)-transformation of FACS cell-sorted CD5 + and CD5- B lymphocytes and unfractionated enriched B lymphocytes from nine IDDM patients treated exclusively with recombinant human insulin, and from four healthy control subjects was performed; a mean of 102-216 microcultures with a mean of 1,000-2,333 cells/microculture for each B-lymphocyte fraction and individual was established. Data show that both CD5 + and CD5- B-lymphocyte subsets from either normal subjects or from IDDM patients receiving recombinant human insulin, contain B lymphocytes committed to the production of IA-IgM as a common element of their repertoire. In contrast, cells committed to the production of IA-IgG were only detected among the CD5- B lymphocyte subset from some IDDM patients. Only one microculture, out of a total of 6,211 screened (from control subjects and patients), in the CD5- B-cell subset from a recently-diagnosed IDDM patient, was found to produce ICA-IgM lambda. This might suggest that the frequency of circulating B lymphocytes committed to the production of ICA is very low even in IDDM patients bearing serum ICA. EBV-transformed B cells producing the ICA-IgM lambda were stabilized and cloned by somatic hybridization technique. This ICA-IgM lambda human monoclonal antibody, designated HY1-MB91, is not polyreactive, but shows a restricted reactivity with human pancreatic islets, failing to react with other human tissues including cerebellar cortex, and lacking rheumatoid factor and anti-DNA antibody activities. It also lacks reactivity with pancreatic islets from other mammalian species (rat, mouse and monkey) as well as with other rat tissues, including cerebellar cortex. The antigen recognized by HY1-MB91 antibody in human islet cells is a cytoplasmic component mostly found in beta cells.

Adolescent↗
PubMed1995

Effects of an individual intensive educational control program for insulin-dependent diabetic subjects with poor metabolic control.

The aim of our study was to evaluate the efficiency of an individual intensive educational control program on improving the metabolic control of insulin-dependent diabetic patients at short- and long-term follow-up. Fifteen insulin-dependent diabetic subjects with poor metabolic control (hemoglobin A1c > 9%) were included. At entry, their knowledge of diabetes (DKQ2 test), total energy intake and its distribution, insulin schedule, technical skill for insulin administration and self monitoring of blood glucose were evaluated. According to the initial evaluation, individual goals were stipulated and monitored in weekly visits. Individual life-style was particularly kept in mind. Thereafter, patients were switched to our ambulatory clinic for outpatients. At 1, 6, 12 and 24 months of follow-up, the items analyzed at the beginning were reevaluated. After 1 month, the program produced a significant decrease in hemoglobin A1c and an increase in knowledge of diabetes. The same beneficial effects were present at 6, 12 and 24 months evaluation compared to those values recorded at entry. There were neither major changes in dietary intake nor insulin schedule nor any increase in the frequency of hypoglycemic episodes. In conclusion, our program (5.2 +/- 0.8 weekly visits) significantly reduced and sustained hemoglobin A1c values close to those levels recommended by multicenter controlled trials. We consider that our program produced two major changes: a long-lasting improvement in knowledge of diabetes and an increase in self-monitoring blood glucose which provided the key for optimal self-regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Pancreatic islet GLUT2 glucose transporter mRNA and protein expression in humans with and without NIDDM.

GLUT2 glucose transporter mRNA has been shown to be underexpressed in pancreatic islets of numerous animal models of non-insulin-dependent diabetes mellitus (NIDDM). It has been proposed that this molecular defect contributes to the pathogenesis of diabetes, although information concerning the expression of GLUT2 in human pancreatic islet tissue is lacking. In contrast to the high abundance of GLUT2 in rat islets, human islets were found to express distinctly low levels of this glucose transporter mRNA and protein. Thus, a sensitive competitive reverse transcription-polymerase chain reaction assay was developed to quantify human GLUT2 mRNA. We obtained pancreases from 4 human organ donors with previously diagnosed NIDDM and 11 nondiabetic donors and found no significant differences in GLUT2 mRNA between the two groups. GLUT2 mRNA was 0.24 +/- 0.08 amol/micrograms RNA (mean +/- SE) in pancreases from humans with diabetes and 0.27 +/- 0.06 amol/microgram RNA in those without this diagnosis. Similarly, human pancreatic islet GLUT2 protein was measured by immunoblot and found to be present at similar levels in two individuals with diabetes relative to six control samples. These results thus demonstrate the existence of species differences in the abundance of islet GLUT2 mRNA and protein. Furthermore, the analysis of islet GLUT2 in a small sample of human organ donors with and without diabetes raises the possibility that decreased beta-cell GLUT2 may not represent a widespread feature of humans with NIDDM.

Base Sequence↗
PubMed1994

Expression of GLUT-2 antisense RNA in beta cells of transgenic mice leads to diabetes.

An insulin response to glucose is required to correct hyperglycemia. Two proteins, the glucose transporter GLUT-2 and the glucose-phosphorylating enzyme glucokinase, have been implicated in the control of glucose metabolism in beta cells. To study the role of glucose transporter GLUT-2 in the regulation of insulin secretion and in the development of diabetes mellitus, we have obtained transgenic mice expressing high levels of GLUT-2 antisense RNA in beta cells. Western blot analysis showed an 80% reduction in GLUT-2 protein in the beta cells of these animals. Islets from transgenic mice showed impaired glucose-stimulated insulin secretion. In addition, much higher levels of blood glucose were detected in transgenic mice than in controls when glucose tolerance tests were performed. These results suggest that the reduction of GLUT-2 in the pancreas could be a crucial step in the development of diabetes mellitus.

Animals↗
PubMed1994

Pancreas in recent onset insulin-dependent diabetes mellitus. Changes in HLA, adhesion molecules and autoantigens, restricted T cell receptor V beta usage, and cytokine profile.

Insulin-dependent diabetes mellitus (IDDM), in which only the pancreatic beta cells are destroyed by the autoimmune response, is the paradigm of organ-specific autoimmunity. As a result of a combination of factors, the number of immunohistologic/cellular/molecular studies of pancreas in IDDM is very limited. We report here studies conducted in the pancreata of two IDDM patients: one newly diagnosed (case 1) and one long standing (case 2). In case 1, we demonstrated the presence of morphologically normal viable beta cells without evidence of viral infection. In both cases the expression of the autoantigens defined by islet cell Abs and by glutamic acid decarboxylase was markedly reduced in the islet cells whereas expression of hsp60, another putative autoantigen, was normal. Over-expression of HLA class I was detected in 58% of the islets in pancreatic sections and in cultured beta cells in case 1 and also in 30% of islets in case 2 but it was not restricted to any insular cell type. In case 1, there was "inappropriate" HLA class II expression in islets cells but it was a rare finding and not beta cell specific. The analysis of the correlation between class I overexpression, residual insulin, and insulitis suggests that the first event is the increase of HLA class I expression. Of adhesion molecules, ICAM-1, VLA, VCAM, and LFA-3 were normal and only ICAM-1 was moderately overexpressed in and around the islets of case 1 insulitis, as was detected by immunofluorescence which showed that 18% of the islets of case 1 had CD8+ lymphocytes as the predominant population. Reverse transcription-PCR demonstrated moderate V beta skewing and the profile of cytokines expected in CTLs: IL-2, IL-4, IL-10, and IFN-gamma negative, perforin positive. In addition, IFN-alpha, IFN-beta, and IL-6 transcripts were detected in the case 1 pancreas, consistent with the existence of a silent viral infection. Overall, the results indicated that, differently from spontaneous animal models of diabetes, in the pancreas of IDDM patients there are no elements of the inductive phase of the autoimmune response.

Acute Disease↗
PubMed1994

Immunocytochemical study of pancreatic islet revascularization in islet isograft. Effect of hyperglycemia of the recipient and of in vitro culture of islets.

We studied the revascularization process of isogeneic islets grafted into the kidney subcapsular space of streptozotocin-induced diabetic and nondiabetic rats by a double-labeling, indirect immunofluorescence technique using a rabbit antiserum to human factor VIII-related antigen (which identifies endothelial cells) and a guinea pig anti-insulin antiserum (which labels pancreatic beta cells). Freshly isolated islets contained a network of capillary endothelial cells, whereas 1-week-cultured islets at 37 degrees C have completely lost their intra-islet endothelial cells. Overnight cultured islets contained only occasional endothelial cells. When these islets were grafted under the kidney capsule of nondiabetic rats, they rapidly acquired a new endothelial cell lining as demonstrated by the positivity of staining for factor VIII-related antigen at day 5 after implantation. On the other hand, 1-week-cultured islets failed to become fully revascularized until day 7 after transplantation. Streptozotocin-induced diabetic rats grafted with 1000 islets normalized their blood glucose values (< 11 mM/L) 2-4 weeks after implantation, whereas transplantation of 2500-3000 islets resulted in normoglycemia after 4.7 +/- 2 days (mean +/- SD). Nevertheless, hyperglycemia of the recipient did not adversely affect the process of revascularization of islet isografts which initiated at day 3 and was almost completed by day 5 after implantation.

Animals↗
PubMed1994

Enzymatic, metabolic and secretory patterns in human islets of type 2 (non-insulin-dependent) diabetic patients.

Islets were isolated by automatic digestion from non-diabetic cadaveric organ donors and from Type 2 (non-insulin-dependent) diabetic subjects. The activity of FAD-glycerophosphate dehydrogenase, but not that of either glutamate dehydrogenase, glutamate-oxalacetate transaminase or glutamate-pyruvate transaminase, was lower in Type 2 diabetic patients than control subjects. Hexokinase, glucokinase and glutamate decarboxylase activities were also measured in islets from control subjects. The utilization of D-[5-3H]glucose, oxidation of D-[6-14C]glucose and release of insulin evoked by D-glucose were all lower in Type 2 diabetic patients than control subjects. The secretory response to the combination of L-leucine and L-glutamine appeared less severely affected. Islets from Type 2 diabetic patients may thus display enzymatic, metabolic and secretory anomalies similar to those often observed in animal models of Type 2 diabetes, including a deficiency of beta-cell FAD-linked glycerophosphate dehydrogenase, the key enzyme of the glycerol phosphate shuttle.

Adolescent↗
PubMed1994

Analysis of the contribution of the HLA system to the inheritance in the Wolfram syndrome.

The Wolfram syndrome (WS) is an autosomal recessive disorder beginning in childhood that consists of four clinical features: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. Its pathogenesis remains unknown, although the tendency to develop this syndrome has been related to some class II antigens of the HLA system. We report six new cases in four families. A review of published data from the genetic features of this syndrome is performed, establishing the high frequency of the HLA-DR2 antigen in the WS (44.4%) compared with a control group (21.9%; relative risk, 2.8) and to patients with Type 1 insulin-dependent diabetes mellitus (Type 1 diabetes) (6.77%; relative risk, 9.7). We also comment the high frequency of the HLA-DQw1 antigen (85.5%) in this syndrome, without statistical significance. A familial segregation study of the HLA haplotypes has been carried out without finding correlation between the autosomal recessive pattern attributed to the WS, and the major histocompatibility complex. In conclusion, whereas HLA may increase susceptibility to the WS, as shown by the existence of an HLA-DR2 association, the major genetic influence on the inheritance of the WS must be at another locus.

Female↗
PubMed1994

Microalbuminuria development in short-term IDDM.

UNLABELLED: To assess risk factors associated with microalbuminuria development in short-term evolution insulin-dependent diabetes mellitus (IDDM) we undertake a cross-sectional study with retrospective examination of the 34 patients diagnosed with IDDM between 1982 and 1983 and followed up for at least 7 years in an outpatient endocrinology clinic. MAIN MEASURES: (1) At IDDM diagnosis: age, sex, parameters of metabolic control (fasting glycemia, HbA1), islet-cell antibodies, insulin autoantibodies, endogenous insulin secretion (EIS) and HLA type. (2) At 1 year evolution: EIS re-evaluation. (3) From IDDM diagnosis (every 3-4 month): body mass index, insulin schedule and dose, and parameters of metabolic control. (4) At 7-year evolution: 24-h urinary albumin excretion (UAE) and arterial blood pressure measurements on two consecutive outpatient controls. Microalbuminuria was defined as UAE above 30 micrograms/min on the two consecutive measurements. After 7-year follow-up, 8 (23.5%; 95% Cl: 9.3 to 37.7%) patients developed microalbuminuria. Their metabolic control was worse (7 years mean HbA1: 10.7 vs. 9.7%; P = 0.04) and 1 year EIS lower (1.9 vs. 7.6 ng/ml.10 min; P = 0.03) than in normoalbuminuric patients. They also had higher prevalence of 'high-normal' arterial blood pressure (P = 0.03) and diabetic retinopathy (P = 0.01) than normoalbuminuric patients did. Stepwise logistic regression analysis showed that diabetic retinopathy was the only independent and significant risk factor related to microalbuminuria development (P = 0.01). We conclude that in subjects with short-term evolution IDDM, microalbuminuria development was associated with glycemic control, EIS and arterial blood pressure levels, however the strongest association was found with diabetic retinopathy occurrence.

Adolescent↗
PubMed1994

Diabetes mellitus in patients with liver cirrhosis.

In spite of the high prevalence of diabetes mellitus (DM) in patients with liver cirrhosis (LC) few studies have focused on the clinical implications of this association. We investigated the clinical and pancreatic-endocrine features of 34 patients who developed DM after LC (Group I). Results were compared with 34 carefully matched patients with only Type II DM (Group II). A standard meal test was performed in 26 patients with normal renal function from each group to assess beta-cell function. Group I patients, less frequently had retinopathy (14.7% vs. 45.5%, P < 0.05) and a family history of diabetes (23.5% vs. 58.8%, P < 0.01). Group I patients also showed signs of enhanced insulin resistance, reflected by higher insulin dose requirements in insulin-treated patients (0.87 +/- 0.10 vs. 0.62 +/- 0.05 IU/kg/day, P < 0.01) and increased basal C-peptide values (0.88 +/- 0.06 vs. 0.68 +/- 0.07 pmol/l, P < 0.05, respectively) than those in Group II. These results suggest that several clinical features, probably related to the hepatopathy, define DM occurring in patients with LC.

Blood Glucose↗
PubMed1994

Nuclear response of pancreatic islets to interleukin-1 beta.

The mechanisms by which interleukin-1 (IL-1) exerts destructive action on the pancreatic islet beta-cells remain elusive. Fragmentation of DNA leading to the activation of poly(ADP-ribose) synthetase was investigated in the present study, by assessing the nuclear response to cytokines in rat pancreatic islets. Nuclear fractions display Mg(2+)-dependent poly(ADP-ribose) synthetase activity catalyzing the incorporation of [adenine-U-14C]NAD, with Ka and Km for Mg2+ and NAD amounting to 0.86 mM and 0.43 mM, respectively. Exposure of the nuclear fraction to rIL-1 beta (10 IU/ml) provoked DNA strand breaks and increased nuclear poly(ADP-ribose) synthetase activity (148.4%, P < 0.01). In intact islets, this nuclear response was observed after 18 h culture in medium containing rIL-1 beta, with a concomitant decrease in NAD (88.5%). Brief periods of pre-incubation (90 min) with rIL-1 beta were unable to induce any nuclear activity. Under these conditions, the presence of IFN-alpha (24 U/ml) and TNF (120 U/ml) was necessary to induce a response to rIL-1 beta. Under the latter experimental conditions, a decrease in NAD content was also observed. The nuclear effects of IL-1 beta were modified by nicotinamide (10 mM), an inhibitor of poly(ADP-ribose) synthetase. It is thus conceivable that an increase in poly(ADP-ribose) synthetase activity together with DNA break is implicated in the beta cytotoxic effect of interleukin-1 beta.

Adenine↗
PubMed1994

Deleterious effect of dithizone-DMSO staining on insulin secretion in rat and human pancreatic islets.

Dithizone (DTZ) is a selective stain for pancreatic islets which facilitates their identification, being of special interest in human islet isolation assessment. Nevertheless, there are few studies concerning its potential toxic effects on islet function. In our study, we have evaluated the effects of DTZ (dissolved in dimethyl sulfoxide [DMSO] 1% w/v) at three different concentrations (2, 10, and 100 micrograms/ml) on insulin response to glucose in human and rat islets. Likewise, we studied the effect of incubation time, in the presence of DTZ at the above-mentioned concentrations, on insulin release. Only when DTZ was employed at low concentrations and for a short period of incubation (10 min) was there no impairment of pancreatic islet function. Moreover, even at this low concentration, DTZ became deleterious for islet function when the incubation period with the dye was prolonged for 30 min. Culture (24 h) of previously stained islets produced a partial recovery of insulin response. In conclusion, our findings indicate (a) DTZ should not be employed to collect islets for functional studies because of its deleterious effect on beta-cell function, (b) DTZ's deleterious effects on beta-cell function should be considered if this dye is used to purify islets by fluorescence-activated cell sorting for transplantation.

Animals↗