I Polymorphism in Sickle Cell Disease in North Morocco.

Sickle cell disease is one of the most common severe monogenic disorders in the world. The -158 I polymorphism (C>T) of the γ-globin gene promoter is known to be associated with increased expression of the γ-globin gene, thus, higher production of Hb F and lesser clinical severity. This study aims to determine the frequency of the I polymorphism and its association with Hb F levels as a modulating factor of sickle cell disease severity in north Moroccan patients.

Hemoglobinopathies in the North of Morocco: Consanguinity Pilot Study.

Consanguinity is a social behavior characterized by the arrangement of marriages between relatives. It coincides generally with the geographic distribution of recessive genetic diseases as it increases the likelihood of homozygosis and, consequently, the incidence of their pathologies in the population. In this pilot study, we assess the effect of inbreeding on the burden of hemoglobinopathies in Northern Morocco.

Alpha-Thalassemia in North Morocco: Prevalence and Molecular Spectrum.

Unlike the other hemoglobinopathies, few researches have been published concerning -thalassemia in Morocco. The epidemiological features and the mutation spectrum of this disease are still unknown. This regional newborn screening is the first to study -thalassemia in the north of Morocco.

Feeding a protective hydrolysed casein diet to young diabetic-prone BB rats affects oxidation of L[U-14C]glutamine in islets and Peyer's patches, reduces abnormally high mitotic activity in mesenteric lymph nodes, enhances islet insulin and tends to normalize NO production.

The present studies were undertaken to examine concomitant diet-induced changes in pancreatic islets and cells of the gut immune system of diabetes-prone BB rats in the period before classic insulitis. Diabetes-prone (BBdp) and control nondiabetes prone (BBc) BB rats were fed for approximately 17 days either a mainly plant-based standard laboratory rodent diet associated with high diabetes frequency, NIH-07 (NIH) or a protective semipurified diet with hydrolyzed casein (HC) as the amino acid source. By about 7 weeks of age, NIH-fed BBdp rats had lower plasma insulin and insulin/glucose ratio, lower insulin content of isolated islets, lower basal levels of NO but higher responsiveness of NO production to IL-1beta in cultured islets, and higher Con A response and biosynthetic activities in mesenteric lymphocytes than control rats fed the same diet.

Labeling of pancreatic glycogen by D-[U-14c]glucose in hyperglycemic rats.

Under conditions of sustained hyperglycemia, glycogen accumulates in pancreatic islets, but not so in acinar pancreatic cells. We investigated whether advantage could be taken of such a situation in the perspective of the noninvasive imaging of the endocrine pancreas. Control rats or animals injected with streptozotocin (STZ) were infused with solutions of D-glucose mixed with a tracer amount of D-[U-14C]glucose, and the radioactive glycogen content of both liver and pancreas was then measured.

Uptake of D-mannoheptulose by normal and tumoral pancreatic islet cells.

D-mannoheptulose was recently proposed as a possible tool to label preferentially insulin-producing cells in the pancreatic gland. In the present study, D-[3H]-mannoheptulose uptake by rat pancreatic islets or dispersed islet cells was found to represent a time-related and temperature-sensitive process inhibited by cytochalasin B. This mould metabolite also inhibited the efflux of D-[3H]-mannoheptulose from prelabelled islets.

Possible participation of an islet B-cell calcium-sensing receptor in insulin release.

The calcium-sensing receptor gene was recently shown to be expressed in rat pancreatic islets and purified islet B-cells. In this study, we investigated the possible role of this receptor in the regulation of insulin release from isolated rat pancreatic islets. Poly-L-arginine (0.

Possible role of diadenosine polyphosphates in glucose-stimulated insulin release: effects of NaF upon metabolic and functional variables in rat isolated islets.

Diadenosine polyphosphates, such as diadenosine triphosphate (A2P3) and diadenosine tetraphosphate (A2P4), were recently proposed to participate in the stimulus-secretion coupling for nutrient-stimulated insulin release. Since NaF, an inhibitor of inorganic pyrophosphatase, was reported to lower A2P3 and A2P4 content in glucose-stimulated pancreatic islets, its effects upon metabolic, cationic, biosynthetic and secretory variables in rat pancreatic islets were investigated in the present study. Up to a concentration close to 0.

New esters of succinic acid and mixed molecules formed by such esters and a meglitinide analog: study of their insulinotropic potential.

Eighteen novel esters of succinic acid, including three mixed molecules formed of both succinic acid and nateglinide, were examined for their insulinotropic efficiency in isolated rat pancreatic islets. The secretory response to these esters at increasing concentrations of both d -glucose and the ester itself allowed to identify five esters judged of potential interest for further investigations. They include three molecules with CH(3)-O-CO-CH(2)-CH(2)-CO-NH-CH(R)-CO-O- sequence and two mixed molecules with a nateglinide moiety.

Long-term effects of glibenclamide and nateglinide upon pancreatic islet function in normal and diabetic rats.

Both control and hereditarily diabetic (Goto-Kakizaki) rats were administered twice daily for 7 days with an oral solution of carboxymethylcellulose containing, when required, glibenclamide (1.0 microgram g-1 body wt.) or nateglinide (50.

Effects of a protective hydrolyzed casein diet upon the metabolic and secretory responses of pancreatic islets to IL-1beta, cytokine production by mesenteric lymph node cells, mitogenic and biosynthetic activities in Peyer's patch cells, and mitogenic activity in pancreatic lymph node cells from control and diabetes-prone BB rats.

The effects of substituting a plant-based control diabetogenic diet (NIH diet) by a protective hydrolyzed casein diet (HC diet) upon selected metabolic and functional variables were recently investigated in Peyer's patch cells, splenocytes, mesenteric lymph node cells, and pancreatic islets from either control (BBc) or diabetes-prone (BBdp) BB rats. In the present work, the plasma d-glucose and insulin concentrations, the protein and insulin content of pancreatic islets, the metabolism of d-glucose, and its insulinotropic action in islets first cultured for 24 h in the absence or presence of IL-1beta, the production of IFN-gamma and IL-10 by mesenteric lymph node cells cultured for 48 h in the absence or presence of concanavalin A, the mitogenic activity of Peyer's patch cells and pancreatic lymph node cells in the absence or presence of the same lectin, and the biosynthetic activity of Peyer's patch cells were measured in the BBc and BBdp rats fed either the NIH or the HC diet. Two major novel findings emerged from this study.

Isomeric and anomeric specificity of the metabolic and secretory response of rat pancreatic islets to glucose pentaacetate.

In the presence of 2.8 mM D-glucose, beta-D-glucose pentaacetate (1. 7 mM) augmented insulin release from isolated rat pancreatic islets more than alpha-D-glucose pentaacetate.

Insulinotropic action of beta-L-glucose pentaacetate.

The metabolism of beta-L-glucose pentaacetate and its interference with the catabolism of L-[U-14C]glutamine, [U-14C]palmitate, D-[U-14C]glucose, and D-[5-3H]glucose were examined in rat pancreatic islets. Likewise, attention was paid to the effects of this ester on the biosynthesis of islet peptides, the release of insulin from incubated or perifused islets, the functional behavior of individual B cells examined in a reverse hemolytic plaque assay of insulin secretion, adenylate cyclase activity in a membrane-enriched islet subcellular fraction, cAMP production by intact islets, tritiated inositol phosphate production by islets preincubated with myo-[2-3H]inositol, islet cell intracellular pH, 86Rb and 45Ca efflux from prelabeled perifused islets, and electrical activity in single isolated B cells. The results of these experiments were interpreted to indicate that the insulinotropic action of beta-L-glucose pentaacetate is not attributable to any nutritional value of the ester but, instead, appears to result from a direct effect of the ester itself on a yet unidentified receptor system, resulting in a decrease in K+ conductance, plasma membrane depolarization, and induction of electrical activity.

Secretory, biosynthetic and cationic responses to 2-(N-PHENYL-INDOYL)IMIDAZOLE in rat pancreatic islets.

The secretory, biosynthetic and cationic effects of a novel insulinotropic agent with an imidazoline structure, 2-(N-phenyl-indoyl)imidazole hydrochloride (RX 871024) was investigated in rat pancreatic islets. In the 1.0-10-microM range, this agent augmented, in a concentration-related manner, the release of insulin from islets incubated at intermediate concentrations of d-glucose (4.

Pancreatic islet responsiveness to D-glucose after repeated administration of repaglinide.

The influence of three daily oral doses of repaglinide (1.0 microg/g body wt.) on plasma insulin and glucose concentrations, pancreatic islet insulin content and both protein biosynthesis and insulin release in isolated islets incubated for 90 min in the presence of either 2.

Stimulation of biosynthetic activity by novel succinate esters in rat pancreatic islets.

Selected esters of succinic acid are currently under investigation as possible insulinotropic agents for the treatment of noninsulin-dependent diabetes mellitus. The aim of the present study was to investigate the effects of ten novel esters of succinic acid upon biosynthetic activity in rat pancreatic islets. In the absence of any other exogenous nutrient, glycerol-3-hydroxy-1,2-dimethyl succinate (0.

Comparison between the insulinotropic potential of ten new esters of succinic acid.

Selected esters of succinic acid are currently under investigation as insulinotropic tools for the treatment of non-insulin-dependent diabetes mellitus. The aim of the present study was to investigate, in isolated rat pancreatic islets, the insulin secretory response to ten novel esters of succinic acid. According to six different methods of comparison, the following hierarchy in insulinotropic potential was established: 4-tert-butyl-succinate < or = glycerol-1,2-dimethylsuccinate-3-hydrogenosuccinate < or = threitol-3-succinoyl-1,2,4-trimethylsuccinate < or = ethanediol-1,2-diethylsuccinate < or = glycerol-1,2-dimethylsuccinate < or = glycerol-3-hydroxy-1,2-dimethylsuccinate < or = arabitol-5-hydroxy-1,2,3,4-tetramethylsuccinate < or = threitol-1,2,4-trimethylsuccinate < or = ethanediol-1,2-dimethylsuccinate < propanediol-1,2-dimethylsuccinate.

Insulinotropic action of the polyacetate esters of metabolized and non-metabolized monosaccharides in pancreatic islets from normal and diabetic rats.

The polyacetate esters of selected monosaccharides were recently found to either stimulate insulin release or inhibit glucose-stimulated insulin secretion in islets from normal rats. The present study extends such findings both to new combinations of either D-glucose or L-leucine and some polyacetate esters and to hereditarily diabetic, as distinct from normal, rats. In the normal animals, 2-deoxy-D-glucose tetraacetate (1.

Insulinotropic action of 1,2,3-Tri(methylsuccinyl)glycerol ester.

A novel ester of succinic acid, 1,2,3-tri(methylsuccinyl)glycerol ester (3SMG), was found to stimulate insulin release from rat pancreatic islets. In the presence of 7 mM d-glucose, a 10 microM concentration of 3SMG was sufficient to cause a significant increase in insulin output. The ester mimicked the effect of other nutrient secretagogues in enhancing the synthesis of islet peptides, with a preferential action on proinsulin as distinct from nonhormonal peptides, in decreasing 86Rb outflow from prelabeled islets, and in stimulating Ca2+ inflow into the islet cells.

Effects of glycerol-1,2-dimethylsuccinate and propanediol-1,2-dimethylsuccinate on insulin release and protein biosynthesis in islets of Goto-Kakizaki rats.

Selected esters of succinic acid are currently under investigation as possible insulinotropic tools in the treatment of non-insulin-dependent diabetes mellitus. Novel esters with high insulinotropic efficiency were recently synthesized. The present study concerns the effects of two of these novel esters, namely glycerol-1,2-dimethylsuccinate (2.

Effect of dehydroepiandrosterone in hereditarily diabetic rats.

Goto-Kakizaki rats (GK rats) were given access for 4 weeks to a diet enriched with dehydroepiandrosterone (DHEA, 0.2 per cent, w/w). The incorporation of DHEA in the food failed to affect significantly body growth, plasma D-glucose and insulin concentrations, pancreatic islet insulin content or the activity of both mitochondrial glycerophosphate dehydrogenase (mGDH) and NADP-malate dehydrogenase (malic enzyme) in islet homogenates.