PubMed Health⌕ Search

Biomedical subjects

A Heurtier

Publications and source records attributed to A Heurtier.

12 recordsLinked to original sources
PubMed2005

Review article: an unexpected virus-host interaction--the hepatitis C virus-diabetes link.

There is now consistent epidemiological evidence for an association between chronic hepatitis C and diabetes. Important, although so far limited longitudinal data, have documented an increased risk for diabetes in patients infected by hepatitis C virus (HCV) especially in those with metabolic risk factors such as a high BMI and older age. HCV encoded proteins might alter insulin signalling thus explaining impaired insulin sensitivity and the occurrence of glycaemic dysregulation even before the cirrhotic stage. The consequences of the association between diabetes and HCV infection are an increased liver fibrosis stage and faster fibrosis progression rate. This article reviews recent human and experimental data on the HCV-diabetes association.

Blood Glucose↗
PubMed2005

PPAR-gamma-agonists' renal effects.

PPAR-gamma ligands, including thiazolidinediones, have recently become clinically available for treating insulin-resistant diabetes mellitus. Accumulating evidence suggests that these drugs not only significantly improve insulin sensitivity but also may have antiproteinuric effects in genetically obese diabetic rodents and patients with type II diabetes and diabetic nephropathy. Moreover, troglitazone reduced expression of ECM proteins and transforming growth factor-beta in glomeruli from streptozotocin-induced diabetic rats. Many other properties including antiproteinuric, hemodynamic, and antihypertensive effects in insulin-dependent diabetes mellitus suggest that PPAR-gamma ligands might have a direct, beneficial renal effect, independent of their capacity to improve glucose tolerance. Besides their antidiabetic effects, thiazolidinediones have been shown to lower blood pressure in diabetic patients with hypertension and patients with diabetic nephropathy through multiple mechanisms. Several studies showed the efficacy of PPAR-gamma agonists to ameliorate the progression of glomerulosclerosis. The effect is independent of insulin effects and could only be partially due to lipid effects. These renal protective effects of PPAR-gamma agonists suggest that they may provide a novel intervention strategy to prevent vascular and glomerular sclerosis.

Animals↗
PubMed2004

Anemia and diabetes.

World Health Organization statistics identify 150 million people with diabetes mellitus worldwide and suggest that this figure may double by 2025. In countries with a western lifestyle, the number of patients admitted for renal replacement therapy with diabetes as a co-morbid condition has increased significantly up to three to four times in a period of 10 years. Diabetes and renal failure are thus tightly linked diseases, and so is anemia. However, whether anemia may be worsened and/or directly, at least in part, caused by diabetes is not clearly elucidated yet. In this article, we review the prevalence, pathophysiology and consequences of anemia in diabetic patients.

Anemia↗
PubMed2001

[Role and modalities of insulin treatment in type 2 diabetics].

INTRODUCTION: The natural history of type 2 diabetes mellitus is characterized by an inescapable and gradual worsening of a decrease in insulin secretion. Thus after several years of progress, less than half of type 2 diabetic patients have good glycemic control. This explains the increase in insulin prescription to type 2 diabetic patients in France in recent years. This work's objective is to take into account recent publication data to clarify the status of and adjustments in insulin therapy. CURRENT KNOWLEDGE AND KEY POINTS: The benefit of insulin treatment-mediated glycemic control optimization on microvascular complications is now proven. However, there is still controversy concerning macrovascular complications. Hypoglycemic risk in type 2 diabetic patients is limited and the main problem with insulin treatment is weight gain. Following failure with treatment by tablets, the most suitable treatment in terms of metabolic improvement, weight gain limitation and treatment adhesion is to add an intermediate insulin injection at bedtime. The next step remains several injections a day, with metformine addition if possible. FUTURE PROSPECTS AND PROJECTS: Therapeutic treatment in type 2 diabetes mellitus may become an earlier start of insulin therapy to preserve the remaining pancreatic insulin reserve. The role of brief and long-lasting insulin analogues, as well as inhaled insulin, which will soon be available, should be specified.

Clinical Protocols↗
PubMed2000

Relative diabetogenic properties of islet-specific Tc1 and Tc2 cells in immunocompetent hosts.

CD8(+) T cells are important effectors, as well as regulators, of organ-specific autoimmunity. Compared with Tc1-type CD8(+) cells, Tc2 cells have impaired anti-viral and anti-tumor effector functions, although no data are yet available on their pathogenic role in autoimmunity. Our aim was to explore the role of autoreactive Tc1 and Tc2 cells in autoimmune diabetes. We set up an adoptive transfer model in which the recipients were transgenic mice expressing influenza virus hemagglutinin (HA) specifically in their pancreatic ss islet cells (rat insulin promoter-HA mice) and islet-specific Tc1 and Tc2 cells were generated in vitro from HA-specific CD8(+) cells of TCR transgenic mice (CL4-TCR mice). One million Tc1 cells, differentiated in vitro in the presence of IL-12, transferred diabetes in 100% of nonirradiated adult rat insulin promoter-HA recipients; the 50% diabetogenic dose was 5 x 10(5). Highly polarized Tc2 cells generated in the presence of IL-4, IL-10, and anti-IFN-gamma mAb had a relatively low, but definite, diabetogenic potential. Thus, 5 x 10(6) Tc2 cells caused diabetes in 6 of 18 recipients, while the same dose of naive CD8(+) cells did not cause diabetes. Looking for the cause of the different diabetogenic potential of Tc1 and Tc2 cells, we found that Tc2 cells are at least as cytotoxic as Tc1 cells but their accumulation in the pancreas is slower, a possible consequence of differential chemokine receptor expression. The diabetogenicity of autoreactive Tc2 cells, most likely caused by their cytotoxic activity, precludes their therapeutic use as regulators of autoimmunity.

Adoptive Transfer↗
PubMed2000

Systemic administration of agonist peptide blocks the progression of spontaneous CD8-mediated autoimmune diabetes in transgenic mice without bystander damage.

Insulin-dependent diabetes is an autoimmune disease targeting pancreatic beta-islet cells. Recent data suggest that autoreactive CD8+ T cells are involved in both the early events leading to insulitis and the late destructive phase resulting in diabetes. Although therapeutic injection of protein and synthetic peptides corresponding to CD4+ T cell epitopes has been shown to prevent or block autoimmune disease in several models, down-regulation of an ongoing CD8+ T cell-mediated autoimmune response using this approach has not yet been reported. Using CL4-TCR single transgenic mice, in which most CD8+ T cells express a TCR specific for the influenza virus hemagglutinin HA512-520 peptide:Kd complex, we first show that i.v. injection of soluble HA512-520 peptide induces transient activation followed by apoptosis of Tc1-like CD8+ T cells. We next tested a similar tolerance induction strategy in (CL4-TCR x Ins-HA)F1 double transgenic mice that also express HA in the beta-islet cells and, as a result, spontaneously develop a juvenile onset and lethal diabetes. Soluble HA512-520 peptide treatment, at a time when pathogenic CD8+ T cells have already infiltrated the pancreas, very significantly prolongs survival of the double transgenic pups. In addition, we found that Ag administration eliminates CD8+ T cell infiltrates from the pancreas without histological evidence of bystander damage. Our data indicate that agonist peptide can down-regulate an autoimmune reaction mediated by CD8+ T cells in vivo and block disease progression. Thus, in addition to autoreactive CD4+ T cells, CD8+ T cells may constitute targets for Ag-specific therapy in autoimmune diseases.

Animals↗
PubMed1999

[Diagnostic criteria for type 2 diabetes].

A new definition of diabetes is just about to be adopted by WHO. The main change concerns the glycemic threshold for diagnosis of diabetes. Its value will decrease from 7.7 mmol/L to 7 mmol/L. This drop is neither the consequence of a methodological change (diabetes remains defined by glycemic values at risk of retinopathy) nor a revision of the gold standard (glycemic value > or = 11 mmol/L at 2 h. post glucose load remains the most accurate criterion for diagnosis). The only purpose of the new definition is to better correlate fasting glycemia with the 2 h. post load value during OGTT. So, the new definition of diabetes with a glycemic value > or = 7 mmol/L will allow to do diagnosis without OGTT. The WHO experts hope that this simplification will improve the earliness of diagnosis and treatment. WHO will propose to categorize 3 groups according to glycemic values: normal values < 6.05 mmol/L, diabetic values > 7 mmol/L, and impaired fasting glucose encompassing values above normal but below the diagnosis cut-off for diabetes (plasma glucose > or = 6.05 mmol/L to < 7.0 mmol/L). This impaired fasting glucose should be considered as a risk factor for diabetes and cardiovascular disease.

Blood Glucose↗
PubMed1999

[Epidemiology of cardio-vascular complications of diabetes].

Epidemiologic studies indicate that hyperglycaemia is responsible for microangiopathy, but that its role in macroangiopathy is more controversial. The relative risk of coronary heart disease (CHD) is 2- to 3-fold greater for diabetic men and 3- to 5-fold greater for diabetic women. It is greater for lower limb arteriopathy (4- to 6-fold) and amputations (10- to 20-fold). Although relative risk is rather constant for different populations, absolute CHD risk depends on other risk factors and the rate of risk in the non-diabetic population. Yet hyperglycaemia is also a causal factor for CHD risk, as demonstrated in cohort studies of Type 1 diabetic patients without diabetic glomerulopathy or any associated CHD risk factors, and especially in diabetic Pima Indians who are genetically protected against hypercholesterolaemia and hypertension. Finally, according to WESDR and UKPDS data, the 10-year risk of cardiovascular mortality increases by 10% for every 1% increase in HbA1c value. Hyperglycaemia can be linked to atherogenesis through several pathways: gluco-oxidation of the extracellular matrix inducing accelerated atherosclerosis, endothelial dysfunction, with a decreased production or inactivation of NO, a thrombogenic tendency, with increase in PAI1, Willebrandt factor and platelet aggregation, and last (but not least) dyslipidaemia subsequent to lipoprotein glycooxidation and increased production of VLDL. Hyperglycaemia was associated with hyperlipoproteinaemia and high plasma triglyceride levels, low plasma HDL levels and high plasma levels of small and dense LDL in three high risk populations: diabetic women, Asian migrants, and the Finnish population of Kupsio. Moreover, impaired glucose tolerance appears to be a CHD risk marker indicative of insulin resistance apparently responsible for atherosclerosis related to an association of CHD risk factors rather than to hyperinsulinaemia. The precedence of insulin resistance over onset of Type 2 diabetes is consistent with the existence, at diagnosis, of clinical complications of atherosclerosis in 20% of cases, as confirmed in the UKPDS study. Finally, though blood glucose control by sulphonylureas and insulin does not appear to be deleterious, these drugs have not shown their efficacy in reducing macrovascular adverse events in Type 2 diabetes, either because the cumulative incidence of events is inadequate (DCCT) or the efficacy of long-term hypoglycaemic effects is not apparent (UKPDS). Moreover, these studies have shown that exogenous as well as endogenous hyperinsulinaemia can lead to increase in weight, with potentially atherogenic android fat distribution. In conclusion, though the correlation between hyperglycaemia and microangiopathy is linear and well-established worldwide (with every 1% increase or decrease in HbA1c resulting in a 30% increase or decrease in microangiopathic events), the same is not true for macroangiopathy, whose prevalence is variable among populations. Thus, CHD mortality due to diabetes is 5-fold lower in France than in Finland, though the Monica study indicates a disparity within the French community.

Cardiac Output, Low↗
PubMed1991

Activation of the CD3/T cell receptor (TcR) complex or of protein kinase C potentiate adenylyl cyclase stimulation in a tumoral T cell line: involvement of two distinct intracellular pathways.

A monoclonal antibody (OKT3) directed against the T cell receptor (TcR)/CD3 molecular complex, as well as a protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate, PMA) were added to a culture of tumoral Jurkat T cells, in order to precise the sequence of intracellular signals leading to T cell activation. The experiments were performed in the presence or in absence of various stimulators of adenylate cyclase (AC) such as forskolin (FK), cholera toxin (CT) or prostaglandin E2 (PGE2). OKT3 increased inositol phosphate (IP) production; in parallel, it induced a slight accumulation of cAMP. The effect was markedly potentiated in presence of FK or CT, and to a lesser extent in the presence of PGE2. FK stimulated adenylate cyclase of Jurkat cell membranes, but the effect was not potentiated by OKT3, suggesting that potentiation of cAMP accumulation requires intact cells and is not mediated by direct receptor coupling. On the other hand, elevated cAMP accumulation induced a negative feedback on IP production. The effect of OKT3 on cAMP was mimicked by A23187, a Ca2+ ionophore, and abolished in the absence of extracellular Ca2+. PMA had the same effect as OKT3 on basal or FK- and CT-induced accumulation of cAMP. In contrast, it inhibited the PGE2 effect on the cyclic nucleotide. After desensitization of PKC by pretreatment with a high concentration of PMA, the phorbol ester was no longer effective. Under those conditions, facilitation by OKT3 of FK-induced accumulation of cAMP was preserved, whereas potentiation by the monoclonal antibody of the PGE2 stimulation of AC was even enhanced. The data indicate that cAMP accumulation indirectly elicited by phospholipase C activation is, at least partly, mediated by IP-dependent Ca2+ mobilization, while PKC is preferentially effective as an inhibitor of PGE2 stimulation.

Adenylyl Cyclases↗