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P Poussier

Publications and source records attributed to P Poussier.

At least 37 records · Page 2Linked to original sources
PubMed1991

The risk of developing disease for siblings of patients with insulin dependent diabetes mellitus.

We analyzed the risk of developing insulin-dependent diabetes mellitus (IDDM) in 411 siblings of patients with IDDM. We found that siblings who had a positive test for antibodies against islet cells (ICA) at the time of diagnosis of the index case had a higher risk of developing IDDM than did those who had negative tests. However, of the ten siblings who developed IDDM, only four were positive at the initial testing. The period of time elapsing from a negative test at screening to a positive test at diagnosis varied but was less than one year in one child. Two of the ten siblings who developed IDDM had negative tests both at screening and at diagnosis. Amongst siblings who were negative at the initial screening, those in whom the index case was diagnosed at a young age had a higher risk of developing IDDM than did those in whom the index case was diagnosed at an older age. The age of the sibling at the time of screening, the sex of the sibling, and a positive family history (one which includes in addition to the index case one or more first-degree relatives with IDDM) did not confer increased risk. Our data suggest that screening for ICA will have to be done often and will have to be continued into adult life in order to identify the 70-80% of diabetics who will be positive at some time in the evolution of their disease.

Adolescent↗
PubMed1990

Abnormal thymocyte maturation in spontaneously diabetic BB rats involves the deletion of CD4-8+ cells.

The object of this study was to further characterize the pathophysiology of the peripheral T lymphopenia in the BB rat. Towards this end, surface markers on unseparated thymocytes and purified thymocyte subsets from age- and sex-matched diabetes-resistant (BBn) and diabetes-prone (BBd) rats were analyzed by two-color flow cytometry. The proportions of thymocytes falling into each of the four main phenotypic subsets were comparable in BBn (n = 9) and BBd (n = 8) rats: respectively, 4.6 +/- 0.6% and 4.4 +/- 0.8%, CD4-8-; 68.1 +/- 1.9% and 71.1 +/- 3.2%, CD4+8+; 18.3 +/- 1.5% and 15.4 +/- 2.3%, CD4+8-; 9.1 +/- 0.9% and 9.1 +/- 1.0%, CD4-8+. In addition, absolute numbers of thymocytes were not significantly different. The levels of expression of CD4, TCR-alpha beta within each thymocyte subset were comparable in BBn and BBd animals as were the anti-TCR-induced proliferative responses of their CD4+8- and CD4-8+ thymocytes. However, phenotypic abnormalities within the CD4-8+ thymocyte subset of the BBd rat were found. A very significant (p less than 0.005) deletion of mature CD4-8+, TCR-alpha beta + thymocytes and a proportional increase (p less than 0.005) of immature CD4-8+, TCR-alpha beta low thymocytes. Moreover, a twofold decrease of CD8 expression by mature CD4-8+ thymocytes was observed in BBd animals. These results suggest that an impaired thymic maturation contributes to the peripheral T lymphopenia of the BBd rat.

Animals↗
PubMed1990

Cluster analysis of an insulin-dependent diabetic cohort towards the definition of clinical subtypes.

Clinical and biochemical data on 111 consecutive insulin-dependent diabetic children enrolled in a longitudinal prospective study were analyzed to determine if more than one clinical expression of Type I diabetes exists. Use of multivariate statistical methods, including Correspondence Analysis, kappa-means clustering and RECPAM (RECursive Partition and AMalgamation), show that there are two well differentiated clinical expressions of IDDM each characterized by a cluster. One is characterized by later age, less severe onset, longer symptom duration, less beta-cell disappearance after 12 months, more females; the other by earlier age, more sudden and severe onset, DR 3/4, earlier disappearance of beta-cell function and more males. RECPAM analysis provides further insight into the structure of the two clusters. An other RECPAM tree identifies low, medium and high risk groups of disappearance of beta-cell function at 12 months after diagnosis.

Adolescent↗
PubMed1990

Adoptive transfer of diabetes in BB rats induced by CD4 T lymphocytes.

Unseparated splenocytes (SPCs) or purified SPC subsets from diabetes-prone BB (BBdp) or diabetic BB (BBd) rats were activated in vitro with either phorbol myristate acetate (PMA) and ionomycin (I) or concanavalin A (ConA). Such activated SPCs were then injected intravenously into 30-day-old BBdp rats, and their capacity to induce adoptive transfer (AT) of diabetes was studied. The proliferative response in vitro of BBd unseparated SPCs or purified W3/13+ SPCs (i.e., T lymphocytes + large granular lymphocytes) to PMA + I far exceeded that of ConA, resulting in mean stimulation indices of 68 and 112 (PMA + I) and 1.9 and 30 (ConA). The incidence of AT was similar when equal numbers of unseparated SPCs from the same BBd donor were injected after activation by either PMA + I + interleukin 2 (PII) or ConA (57 vs. 50%, respectively); however, injection of PII-activated and macrophage-depleted W3/13+ SPCs from BBd animals resulted in a significantly higher incidence of AT (90%, P less than 0.05). As few as 0.5 x 10(6) PII-activated W3/13+ SPCs were sufficient to induce AT. Sixteen percent of recipients developed diabetes after injection of activated W3/13+ cells from 40-day-old BBdp donors. To determine which W3/13+ cells might mediate such transfer, purified and PII-preactivated CD4 T lymphocytes from BBd rats were injected, and they succeeded in AT in 44% of the recipients. Preactivated BBd B lymphocytes were unable to induce AT. Although a possible role for large granular lymphocytes cannot be excluded, the results demonstrate that in the BB rat, the beta-cell destruction can be induced by CD4 T lymphocytes.

Animals↗
PubMed1988

Immunological responses to chronic heat exposure and food restriction in rats.

Immunological variables were studied in rats chronically exposed to high environmental temperature (35 degrees C). Responses were compared with those of rats at 25 degrees C both fed ad libitum and pair fed to the decreased intake found in heat-exposed rats. Heat-exposed rats showed slower delayed-type hypersensitivity responses to keyhole limpet hemocyanin. They showed lower counts of peripheral blood total T cells (OX19+) as well as helper T cells (W3/25+) and smaller numbers of splenic T cells. The thymus was decreased in size. Increased levels of serum IgG antitetanus toxoid antibodies were found in heat-exposed rats. [3H]-thymidine incorporation into Concanavalin A (ConA)-stimulated splenic lymphocytes was decreased in pair-fed rats but not significantly altered in heat-exposed rats compared with controls. Heat exposure alters some aspects of both cellular and humoral immune function in a manner different from that induced by comparable food restriction without heat exposure.

Animals↗
PubMed1988

Prospective study of predictors of beta-cell survival in type I diabetes.

We conducted a prospective study to describe the course of the pancreatic beta-cell function from the time of clinical diagnosis of insulin-dependent (type I) diabetes to determine whether DR type, presence of islet cell antibodies (ICA), presence of insulin antibodies (IA), age at onset, and sex could help in the prediction of residual endogenous insulin secretion. A cohort of 68 children was followed for 18 mo after diagnosis of type I diabetes. The outcome variables selected for analysis were 1) serum C-peptide peak concentration after a Sustacal meal, 2) time of disappearance of the serum C-peptide response, and 3) time after diagnosis at which the maximal serum C-peptide response was observed. After institution of insulin therapy, serum C-peptide peak concentrations rose temporarily for 1-6 mo and declined thereafter. Multivariate analysis of the data showed that DR type (P = .2488) and presence of IA (P = .1604) had no effect on serum C-peptide over time, but sex (P = .0146), age at onset (P = .0002), and presence of ICA (P = .0147) significantly contributed to the variation of serum C-peptide over time. Furthermore, age at onset, presence of ICA, and sex were also the only significant predictors of the time of disappearance of the beta-cell function. The relative risks of beta-cell-function disappearance were 0.87 (P = .0015), 9.43 (P = .0181), and 2.25 (P = .0468), respectively. In conclusion, there are distinct variations in the natural course of the beta-cell function in type I diabetes. beta-Cell-function survival is significantly shortened the younger the subject is at disease onset, if ICA are present at diagnosis, and if the subject is male.

Adolescent↗
PubMed1986

Production and characterization of a monoclonal islet cell surface autoantibody from the BB rat.

Islet cell surface autoantibodies are present in the serum of the spontaneously diabetic BB rat. The availability in large quantities of such autoantibodies should help us understand their significance in vivo. Fusions between BB rat lymphocytes and rat myeloma cells were screened by cellular enzyme linked immunosorbent assay and indirect immunofluorescence on rat living cells. They resulted in a stable hybridoma, called IC2, secreting a monoclonal immunoglobulin M specific for the surface of rat islet cells. This monoclonal antibody was found to bind to the surface of 56% normal rat islet cells and 72% rat insulinoma cells. Protease treatment of rat islet cells resulted in a subsequent 72-100% binding inhibition of IC2 to the surface of these cells, suggesting that IC2 specific antigen is a protein.

Animals↗
PubMed1985

Time course of islet cell antibodies in diabetic and nondiabetic BB rats.

The BB rat develops a spontaneous type I diabetic syndrome with anti-islet autoimmunity. Sera from diabetic and nondiabetic BB rats (from diabetes-prone litters), nondiabetic BB rats (from low-risk lines), and nondiabetes-prone Sprague-Dawley rats were collected twice a week from age 40 days to 160 days. Sera were tested for: (1) complement-dependent toxicity to 51Cr-labeled islet cells in vitro; (2) immunoglobulin binding to RIN-5 F insulinoma cells; and (3) ability to selectively suppress insulin secretion from normal islets in vitro. All sera from rats that subsequently became diabetic or glucose-intolerant were toxic to islet cells from various rat strains in the presence of complement. They were toxic neither to hepatocytes nor to fibroblasts. The toxic potency was associated with the globulin fraction. It was, in most cases, maximal either before or immediately after the onset of the disease. Sera from the nondiabetes-susceptible BB rats and the rats which, in diabetes-prone litters, died too early to be classified tended toward greater toxicity to islets. Immunoglobulins from diabetic sera bound to RIN-5 F cells more than did the serum globulins from other groups, their maximal binding capacity occurring after the onset of diabetes. Furthermore, BB diabetic sera were capable of selectively inhibiting the insulin secretion from normal rat islets in vitro either in the presence or, in some cases, in the absence of complement. The A- and D-cell functions were not suppressed. The combination of such results suggests the presence of one or more antibodies capable of binding to beta cells, inhibiting their function, and inducing their lysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Liver perisinusoidal fibrosis in BB rats with or without overt diabetes.

Perisinusoidal fibrosis is a vascular lesion observed in the liver of type I diabetic patients. To investigate whether this liver lesion is secondary to hyperglycemia or whether it represents a separate collagen vascular disorder, the authors studied the structure of liver sinusoids in genetically susceptible BB rats in which a spontaneous diabetes develops similar to human type I diabetes. Seven diabetic insulin-treated BB rats, 7 nondiabetic BB rats, and 6 control non-BB rats were studied. Histologic abnormalities of the collagen network were detected on trichrome-stained sections. Perisinusoidal collagen fibers were quantified ultrastructurally by the point-counting method. All control non-BB rats had normal livers; 86% of the diabetic as well as 71% of the nondiabetic BB rats displayed localized sinusoidal thickening corresponding ultrastructurally to perisinusoidal fibrosis; in these abnormal rats the percentage of collagen fibers per sinusoid unit was significantly higher than that in controls. Fibrous septa (2 diabetic and 5 nondiabetic BB rats) and liver nodulation (3 diabetic and 1 nondiabetic BB rats) were also observed. Perisinusoidal fibrosis is a frequent liver vascular abnormality in a strain of rats genetically predisposed to the development of type I diabetes. The lesion is independent of the presence of diabetes. These observations suggest that liver perisinusoidal fibrosis in patients with type I diabetes might be linked to a genetic abnormality rather than to hyperglycemia per se.

Animals↗
PubMed1984

Islet cell surface and lymphocyte antibodies often precede the spontaneous diabetes in the BB rat.

The diabetic syndrome of the BB rat shows many homologies with that of human insulin-dependent diabetes and evidence that the onset of the disease is associated with the presence of autoantibodies, including islet cell surface antibodies. In this study, sera were sampled serially from weaning to 157 days of age from 26 BB rats in two low-incidence litters, and 22 rats of three high-incidence litters. Clinical and metabolic variables were monitored concurrently with blood lymphocyte counts. Islet morphology was correlated at sacrifice. In the high-incidence litters, eight rats developed insulin-dependent diabetes, five impaired glucose tolerance, and the remaining nine all showed insulitis. In the low-incidence litters, only one animal showed impaired glucose tolerance and another insulitis. In the high-incidence litters 16 rats (73%) had islet cell surface antibodies compared with 4 out of 26 (15%) low-incidence controls (p less than 0.002). Antibodies reactive with Wistar rat spleen lymphocytes were present in all high-incidence rats compared with 19% (5 out of 26) among the control litters (p less than 0.002). Time courses of islet cell surface and lymphocyte antibody appearance and their peak values varied, but already at weaning the levels of both antibodies were increased among the high-incidence litter rats (p less than 0.001). Islet cell surface and/or lymphocyte antibodies were therefore present in the majority of animals at an age where neither morphological nor metabolic evidence of the diabetic syndrome were yet detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Glucoregulatory and metabolic responses to heat exposure in rats.

To determine the possible role of altered secretion and effects of insulin in fuel homeostasis during heat exposure, the hormonal and metabolic milieu of three groups of rats were studied. The first was placed at 35 degrees C for 12 days (HE), the second was pair-fed (PF) to the first but maintained at 23 degrees C, and the third was allowed to eat ad libitum at 23 degrees C (C). Plasma insulin, glucagon, glucose, and free fatty acids (FFA), and blood lactate, pyruvate, 3-hydroxybutyrate, and individual amino acids were determined. To further characterize glucoregulation, an intraperitoneal glucose tolerance test (1 mg/g body wt) and isotopic glucose turnover (primed infusion of [3-3H]glucose) were performed. In HE rats, weight was constant for the last third of the period, and metabolic state 4 h after food removal was characterized by euglycemia but hypoinsulinemia, elevated blood pyruvate and FFA, and normal 3-hydroxybutyrate compared with C. Lowered levels of branched-chain amino acids and arginine were found. Fourteen hours after food removal glucose turnover was decreased. However, glucose intolerance accompanied by hyperinsulinemia was also found. Many of these changes were also seen in PF, including constant weight, fasting euglycemia, hypoinsulinemia, elevated FFA, and lowered valine and isoleucine. In contrast, pyruvate concentrations were normal, that of 3-hydroxybutyrate was elevated, and the decrement in glucose turnover was smaller than in HE rats. The glucose tolerance was similar to that of HE but accompanied by hypoinsulinemia. The results in HE suggest decreased energy metabolism, insulin secretion altered in a complex manner, and altered insulin action.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1983

Insulin and glucagon secretion in BB wistar rats with impaired glucose tolerance.

Glucose tolerance and insulin secretion were studied in non-diabetic littermates (n = 154) of BB diabetic rats, aged 4-6 months. Initial screening involved two intraperitoneal glucose tolerance tests (0.2 g/100 g body weight) performed one week apart. Nineteen rats (12%) were found to have impaired tolerance which persisted in 14 (74%) (group 1) and was transient in five animals (group 2). Seven rats progressed to overt diabetes in group 1, but none in group 2. Group 1 was characterized by (a) sustained abnormalities in glucose response to oral and intraperitoneal glucose, as well as intraperitoneal tolbutamide and arginine; (b) fasting hypoinsulinaemia; (c) decreased insulin response to glucose and tolbutamide; (d) suppression of the early and late phases of immunoreactive insulin response to intravenous glucose; (e) no systematic abnormalities in glucagon secretion; and (f) the presence of significant insulitis. The group 2 rats had (a) normal glycaemic response to oral and intraperitoneal glucose, tolbutamide and arginine on further testing; (b) normal fasting insulin but excessive insulin response to glucose and tolbutamide, but not to arginine, and (c) mainly normal islet morphology. Thus, impaired glucose tolerance may occur in BB rats with either hypoinsulinaemia or hyperinsulinaemia.

Animals↗
PubMed1983

Arginine-induced glucagon secretion in the spontaneously diabetic BB Wistar rat.

The spontaneously diabetic BB Wistar rat shows many characteristics analogous to human insulin-dependent diabetes (IDDM). These include inappropriately normal immunoreactive glucagon in the presence of hyperglycemia, absolute hyperglucagonemia with severe ketosis, and hyperresponsiveness to exogenous arginine in vivo. We used an in situ pancreas preparation to further study portal vein glucagon responses to intravenous arginine. In normal rats, magnitude of response was correlated with prestimulation levels. Basal levels were significantly increased in hyperglycemic diabetics compared to controls, but responses to arginine were attenuated in both absolute and relative terms. Comparisons of responses with poor and good prior diabetes control showed no significant differences. Thus, a further anomaly of glucagon secretion has been identified in these rats.

Animals↗
PubMed1983

Clinical forms and natural history of the diabetic syndrome and insulin and glucagon secretion in the BB rat.

The spontaneous diabetes of the BB Wistar rat has many homologies to that of human insulin-dependent diabetes mellitus (IDDM). The different degrees of severity and varying time courses of the islet lesion lead to a spectrum of metabolic derangements and corresponding clinical presentations. Thus, animals with the diabetic phenotype may show only mild insulitis, more severe insulitis with glucose intolerance, marked beta cell destruction with overt but stable diabetes, or total beta cell loss with classic IDDM. Progression of the lesion and clinical presentation occur, as well as occasional reversion to less severe forms. Hence, the definition of a susceptible animal as nondiabetic requires demonstration of normal islets and normal glucose tolerance. In animals showing sustained impaired glucose tolerance (IGT), insulin secretion is most commonly impaired in response to glucose and tolbutamide, though not necessarily to arginine. However, a subgroup with IGT shows hyperinsulinemic responses. Glucagon secretion appears normal in IGT. With overt IDDM, insulin levels are low and unresponsive. However, inappropriate normoglucagonemia, and abnormal regulation of IRG secretion by arginine and neural factors accompany IDDM. This "model" syndrome has already demonstrated its utility for insights into the pathophysiology of IDDM, many of which may be applicable to the further study of the analogous human syndrome.

Animals↗
PubMed1983

Passive transfer of insulitis and lymphopenia in the BB rat.

The BB rat spontaneously develops insulitis followed by impaired glucose tolerance (IGT) or an insulin-dependent diabetic (IDDM) syndrome. Passive transfer of insulitis from newly detected diabetic BB rats to nude mice has been achieved by intraperitoneal or intravenous injection(s) of blood and spleen lymphocytes. After a single injection of cells, 37% of the mice (n = 72) showed insulitis with a mean intensity of 1.9 +/- 0.3 (on a scale of 0 to 3). After three successive injections, 58% of the recipient mice (n = 12) showed insulitis with a mean intensity of 2.5 +/- 0.3. Only one of the control mice (n = 45) demonstrated mild insulitis. The small number of affected islets (13% after a single injection, 17% after three injections) probably explains the absence of random or post IP glucose hyperglycemia in the recipient mice. During this study the yield of lymphocytes in diabetic BB rats was found to be consistently lower than in control normal Wistar rats. This lymphopenia was found not only in the blood and the spleen but also in the thymus and the lymph nodes. Peripheral blood lymphopenia antedated glucoregulatory disturbances. All rats showing either insulitis alone or with IGT or IDDM were lymphopenic. None with normal lymphocyte counts developed any abnormality. Diabetics showed a marked decrease in the proportions of T+ lymphocytes in all tissues whereas the proportion of B(Ia+) lymphocytes was normal in blood, spleen, and thymus but increased in lymph nodes. However, in absolute terms both T+ and Ia+ lymphocytes were decreased. The subset decreased by the greatest proportion in all tissues, except in the thymus was the one that includes helper T lymphocytes. This lymphopenia could be related to the presence of circulating antilymphocyte antibodies. These results strongly support a role for altered immunity in the etiology of the syndrome. If the observed anomalies of lymphocyte numbers and subsets are responsible, then a novel mechanism different from most other "autoimmune" disorders must be implicated.

Animals↗
PubMed1983

Humoral immunity in the spontaneously diabetic BB rat.

Litters of BB rats with an expected high and low incidence of insulin-dependent diabetes were followed from weaning until the age of about 140 days. Islet cell surface antibodies (ICSA) and lymphocyte antibodies (LA) were determined in a radioligand assay with fixed rat insulinoma (RIN 5F) cells, an insulin-secreting cell line, or spleen lymphocytes. In the low-incidence litter, 2 out of 14 rats had ICSA and LA; one showed insulitis at the end of the study. In the high-incidence litter, 3 out of 7 developed diabetes; all 3 showed ICSA at weaning. The remaining 4 showed insulitis. All 7 diabetes-susceptible rats had ICSA and LA at some time during the study. It is concluded that there is a high incidence of circulating ICSA and LA in the spontaneously diabetic BB rat. The antibodies can often be detected before the onset of diabetes, and may be implicated in the beta-cell destructive process and in the lymphocytopenia characteristic of the syndrome.

Animals↗