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Biomedical subjects

R Gomis

Publications and source records attributed to R Gomis.

At least 163 records · Page 9Linked to original sources
PubMed1989

Islet-cell antibodies: markers of a more severe insulin-dependent diabetes mellitus?

The aim of the present study was to analyze if an association exists between metabolic condition, C-peptide secretion and islet-cell antibody (ICA) presence in insulin-dependent diabetes mellitus (IDDM) at the clinical onset of the disease. Two hundred and nine IDDM patients were studied at diagnosis. 89% of the subjects showed residual C-peptide secretion that correlated inversely with blood glucose and glycosylated hemoglobin at diagnosis and with insulin requirement at discharge. Islet-cell antibodies were detected in 68.6% of the patients, complement-fixing ICA in 30% and insulin autoantibodies in 17.3%. Islet-cell antibody positive patients had a lower glucagon stimulated C-peptide than ICA negative subjects (0.41 +/- 0.22 versus 0.54 +/- 0.25 nmol/l, p = 0.005). However patients with high titers of ICA expressed in JDF units (JDF greater than 20) showed similar C-peptide secretion than ICA positive patients with a low level of JDF (JDF less than 20). When acid-base condition was analyzed patients on ketoacidosis at diagnosis had significant higher insulin requirement, lower C-peptide secretion and higher prevalence of ICA compared to patients that were not ketotic at diagnosis. Our findings suggest that residual beta-cell secretion plays a role on metabolic condition at diagnosis of IDDM and that ICA may be the markers of a more severe form of IDDM.

Adolescent↗
PubMed1988

The effect of hypoglycemic sulfonylureas on human red blood cell transglutaminase activity.

We have examined the effect of glipizide, a hypoglycemic sulfonylurea, upon transglutaminase activity in human red blood cells. In a first series of experiments the in vitro effect of the drug was assessed. The results obtained showed that glipizide inhibits transglutaminase activity in human red blood cells. In a second approach, glipizide was administered orally to six type 2 diabetic patients during 3 months, in order to evaluate the long-term effect upon transglutaminase activity. Again, glipizide induced a significant decrease in the enzyme activity in blood red cells (P less than 0.01). We suggest that treatment of type 2 diabetes mellitus with hypoglycemic sulfonylureas could improve insulin effects by inhibiting cellular transglutaminase activity.

Calcium↗
PubMed1988

Hyperglucagonism and glucagon resistance in cirrhosis. Paradoxical effect of propranolol on plasma glucagon levels.

Propranolol, a non-selective beta-blocker, is known to decrease glucagon release in normal subjects. The present study was aimed at investigating the effects of propranolol on the hyperglucagonism commonly observed in patients with cirrhosis. Eight cirrhotic patients and 6 matched healthy controls were studied. The plasma concentrations of glucagon, insulin, c-peptide and glucose were measured in basal conditions and after stimulating glucagon secretion by an i.v. infusion of arginine (0.4 g/kg/30 min). The study was repeated 24 h later after inducing beta-blockade by the i.v. infusion of propranolol (10 mg). In baseline conditions, patients with cirrhosis, despite normal levels of insulin and glucose, had a marked hyperglucagonism (654 +/- 303 pg/ml vs. 269 +/- 90 in controls, P less than 0.01). Prior to propranolol, arginine infusion caused greater glucagon release in cirrhotics (71 +/- 31 ng.h.ml-1) than in controls (33 +/- 17 ng.h.ml-1, P less than 0.02), but despite a similar insulin secretion (assessed from c-peptide), blood glucose did not increase. After propranolol, glucagon secretion decreased as expected in controls (29 +/- 12 ng.h.ml-1, P less than 0.05) but experienced a paradoxical increase in cirrhotics (113 +/- 64 ng.h.ml-1, P less than 0.05). Again, despite the marked increase in glucagon release, there was no increase in glucose production, providing further evidence of the glucagon resistance that accompanies hyperglucagonism in cirrhosis. Our results suggest that hyperglucagonism with glucagon resistance might be the initial disturbance in carbohydrate metabolism in patients with cirrhosis. Contrary to what could be expected, propranolol does not correct but further accentuates this disturbance.

Adult↗
PubMed1988

Presence of insulin autoantibodies at clinical diagnosis of diabetes mellitus type I predicts loss of beta cell function.

Recently the spontaneous development of insulin autoantibodies (IAA) has been detected in patients at diagnosis of Type I diabetes mellitus before the beginning of insulin treatment. The present study was undertaken to investigate if the presence of IAA at clinical onset of IDDM may act as a new marker of the beta cell function. The results obtained showed that IAA were present in 44% of newly diagnosed diabetic patients before therapy. Patients without IAA displayed a higher C-peptide secretion than those with IAA, at six months (12.11 +/- 5.08 versus 5.88 +/- 3.25 ng/ml/10 min.)(X +/- SD) and at twelve months (10.45 +/- 3.05 versus 4.90 +/- 5.25 ng/ml/10 min)(X +/- SD) of the follow up period. HbA1 levels, and insulin requirements were similar in both groups (IAA+ and IAA-). We conclude that the presence of insulin autoantibodies at clinical diagnosis, before initiating insulin treatment, may well predict the loss of the beta cell function.

Adolescent↗
PubMed1988

[Effect of tolbutamide on the activity of transglutaminase].

Five obese patients were studied during 7 days, 750 mg of tolbutamide, per os, was given. Blood samples were drawn at basal state and at 3, 5, 7 days during the treatment and 6 days after it. The values of transglutaminase activity (that in the basal state were similar to that in the controls) decreased significantly at the seventh day of treatment (72.3%). This decrease was transient and rapidly returned to the basal values when the drug was suspended. The results suggest that sulfonylureas exert in part their hypoglucemic effect by modificating the insulin receptor binding through the inhibition of transglutaminase activity.

Adult↗
PubMed1988

Diazoxide-induced long-term hyperglycemia. I. Preservation of B-cell insulin-releasing capacity.

Although several models of experimental diabetes mellitus are currently available, none of them appears to be optimally suited to study the possible deleterious effect of sustained hyperglycemia upon biochemical and functional variables in pancreatic islet cells in the absence of chronic stimulation of secretory activity. In the present study, oral diazoxide administration (0.33 g/Kg body wt. thrice per day for three days) to rats was used to cause both hypoinsulinemia and hyperglycemia (greater than or equal to 10.0 mM), the latter persisting, albeit at a somewhat lower level, for at least 1-2 days after cessation of diazoxide treatment. Ten hours after the last administration of diazoxide, the secretory response of isolated islets to D-glucose over 90 min incubation was not impaired. It is proposed that such a model may help to dissociate the influence of hyperglycemia itself upon islet cell behaviour from the consequences of sustained hypersecretion of insulin.

Animals↗
PubMed1988

Erythromelalgia associated with acute diabetic neuropathy: an unusual condition.

Erythromelalgia is a syndrome characterized by erythema, burning pain and increased skin temperature of the affected extremities. It can be either primary (idiopathic) or secondary, but both forms require a critical temperature between 32-36 degrees C to provoke the crisis. Among the secondary forms, its association with diabetes mellitus is infrequent and its significance is little known. The histological studies have been fundamentally performed in patients with this syndrome affected by thrombocythemia; vascular thrombosis and fibromuscular intimal arteriolar proliferation were the prominent findings not corroborated in patients with the primary form. We studied one patient with acute diabetic neuropathy who developed erythromelalgia. We noted the absence of histopathological lesions, suggesting a disorder in vascular motility regulation favored by the severe neuropathy, without being able to discount a possible immunomediated mechanism. We describe the favourable evolution of the patient after treatment with aspirin and methysergide.

Acute Disease↗
PubMed1987

Prevalence of islet cell antibodies, insulin antibodies and hyperglycaemia in 2291 schoolchildren.

Islet cell antibodies, insulin antibodies and hyperglycaemia were investigated in 2291 healthy schoolchildren. Eight of the subjects had islet cell antibodies and eight had insulin antibodies. However, no schoolchild who was positive for islet cell antibodies also had insulin antibodies present. Hyperglycaemia was observed in five children but neither islet cell antibodies nor insulin antibodies could be detected in the sera from these particular subjects.

Adolescent↗
PubMed1987

Acute effect of glibenclamide upon red cell transglutaminase activity in diabetic patients.

The acute effect of glibenclamide, a hypoglycemic sulfonylurea, upon transglutaminase activity was investigated in 6 type II diabetic patients by perfusing 1 mg glibenclamide during 1 h. Blood samples were drawn 0, 10, 20, 30, 60 min during and 30 and 60 min after perfusion to determine insulin, glucose and transglutaminase activity. No significant modifications in plasma insulin, plasma glucose and transglutaminase activity in red cells was induced by glibenclamide perfusion. Nevertheless, glibenclamide induced a significant decrease (p less than 0.005) in transglutaminase activity after 20 min of perfusion (629.83 +/- 53.08 and 521.18 +/- 43.92, mean +/- SE, at 0 and 20 min). No correlation was observed between glucose or insulin plasma levels and transglutaminase activity.

Adult↗
PubMed1986

The coupling of metabolic to secretory events in pancreatic islets: inhibition by 2-cyclohexene-1-one of the secretory response to cyclic AMP and cytochalasin B.

In rat pancreatic islets perifused in the presence of 2-cyclohexene-1-one (CHX; 1.0 mM), the secretory response to either D-glucose or 2-ketoisocaproate, but not that evoked by the association of L-leucine and L-glutamine, was severely decreased. This coincided with a decreased stimulation of [45Ca] efflux from prelabelled islets, whereas the inhibitory action of D-glucose or 2-ketoisocaproate upon both [86Rb] and [45Ca] efflux appeared little or not affected. In the presence of D-glucose, the islets exposed to CHX were virtually unresponsive to either forskolin, theophylline or cytochalasin B. A severe decrease in the secretory response to forskolin was also observed in CHX-treated islets exposed to L-leucine and L-glutamine. Except for a somewhat lower sensitivity to NaF, no major change in adenylate cyclase activity or cyclic AMP production was observed in CHX-treated islets. The activity of protein kinase A was decreased in such islets but its responsiveness to cyclic AMP appeared unaltered. Transglutaminase activity was severely decreased in homogenates derived from CHX-treated islets. These findings suggest that CHX, possibly by lowering the GSH content of islet cells, impairs the functional capacity of the effector system for insulin release, in addition to and independently of any effect that it may exert upon nutrient catabolism and cationic fluxes in the islet cells.

Adenylyl Cyclases↗
PubMed1986

Glucose-induced activation of transglutaminase in pancreatic islets.

Transglutaminase activity in rat islet homogenates was increased after preincubation of the islets at high glucose concentration, and severely decreased after preincubation in the presence of either 1,2-bis(2-chloroethyl)-1-nitrosurea or 2-cyclohexene-1-one. The stimulatory action of glucose was still observed when the islets were preincubated in the absence or extracellular Ca2+. The enzymic activity was decreased by NAD+ or NADP+ but not NADH or NADPH, and inhibited by GSSG more than by GSH. These findings suggest that the glucose-induced activation of transglutaminase may be related to induction of a more reduced redox state with subsequent change in thiol-disulfide balance.

Animals↗
PubMed1985

Facilitation of insulin release by N-p-tosylglycine.

N-p-tosylglycine, which inhibits transglutaminase activity in islet homogenates, was found to cause a rapid and sustained facilitation of insulin release evoked by D-glucose, L-leucine or the association of Ba2+ and theophylline in intact islets. Such a facilitating action could not be attributed to any obvious effect upon either nutrient oxidation or 45Ca net uptake and outflow. It failed to be reproduced by glycine, N alpha-p-tosyl-L-arginine methyl ester or N alpha-p-tosyl-L-lysine methyl ester. N-p-tosylglycine (5.0 mM) slightly enhanced insulin release evoked by a high concentration of glucose (16.7 mM) and failed to affect significantly the secretory response to the association of L-leucine and L-glutamine or that of D-glucose and gliclazide. N-p-tosylglycine failed to affect the incorporation of [2,5-3H]histamine in trichloroacetic acid-precipitable material in intact islets. These results suggest that N-p-tosylglycine interferes with a late event in the secretory sequence, possibly at the level of the cell boundary, rather than inhibiting the crosslinking of intracellular proteins.

Acyltransferases↗