Beta Cells In Islets Of Langerhans Research Articles

Ajwa seeds (Phoenix dactylifera L.) suspension exerted antidiabetic and antihyperlipidemic effects against streptozotocin-induced diabetes in rats by downregulating insulin expression in the pancreatic beta islets

Objectives: This study investigated the antidiabetic and antihyperlipidemic effects of the powdered seeds of Ajwa Al-Madina in streptozotocin (STZ)-induced diabetes in rats. Besides investigating the possible underlying mechanisms. Methods: Rats were assigned to one of six groups (n = 5) as follows: normal control, vehicle control, Ajwa seeds control, diabetic control, Diabetic + Metformin, and Diabetic + Ajwa seeds. Metformin and Ajwa seeds were injected into rats orally via oral gavage 6 days/week along 4 weeks period Results: Ajwa seeds decreased fasting serum glucose, increased fasting serum insulin and decreased fasting serum triglycerides cholesterol, low-density lipoprotein, and increased fasting serum high-density lipoprotein. Besides, it upregulated insulin protein immunoexpression in the beta cells of Langerhans islets. Ajwa seed also preserved the normal histological structure of the pancreatic beta cells tissue. Conclusion: Ajwa seeds produced significant hypoglycemic and hypolipidemic effects in diabetic rats mainly through enhancement of insulin secretion. The plant is a promising adjunctive therapy in diabetes mellitus treatment.

Effects of Urtica dioica hydro-alcoholic extract on blood serum glucose and lipid profiles of female Wistar rats with long-term estrogen deficiency.

In this study, the effects of Urtica dioica hydro-alcoholic extract were investigated on the blood glucose and lipid profiles of female ovariectomized and non-ovariectomized rats. In total, 32 adult female rats were divided into four groups (eight each) including control and ovariectomy groups as well as non-ovariectomy and ovariectomy groups treated with 200 mg kg-1 of Urtica dioica extract orally in the last five weeks of the study starting from the week 56th. The duration of the study was 60 weeks. Glucose, serum lipid profiles and pancreatic pathological alterations were determined in these groups at the end of experiment. Serum glucose, triglyceride (TG), very-low-density lipoprotein (VLDL), and TG/high-density lipoprotein (HDL) ratio indicated a significant increase in the healthy female rats under treatment with Urtica dioica extract compared to others. The TG, cholesterol, HDL, low-density lipoprotein (LDL) and VLDL showed a significant increase in menopaused rats compared to others. The interaction of consuming Urtica dioica extract and ovariectomy caused significant decreases in glucose, TG, VLDL, HDL/LDL ratio and TG/HDL ratio. Consumption of Urtica dioica extract by non-menopaused rats damaged the beta cells in Langerhans islets. Results of the present study revealed that the consumption of Urtica dioica extract is not beneficial and has diabetogenic effects in female non-ovariectomized rats compared to ovariectomized ones.

Hyperinsulinisme congénital révélé par une mort inattendue de l’enfant

We report the case of a girl of 5 and a half months admitted for discomfort and consciousness loss at home and supported on sudden infant death protocol. Workup was negative. Autopsy showed only signs of asphyxia. Microscopic examination of the pancreas showed hypertrophic beta cells of Langerhans islets, explaining death linked to severe hypoglycemia by inappropriate insulin hypersecretion. This observation highlights the importance of the management of sudden infant unexpected death according to the protocol of the National Health Authority, which includes an autopsy with complete sampling, which in this case resulted in a diagnosis of unknown disease the lifetime of the child.

Molecular genetics of type 1 diabetes mellitus: Achievements and future trends

Type 1 diabetes mellitus (T1DM) is a widespread, severe disease which results from the immunologically mediated destruction of the beta-cells of pancreatic Langerhans islets. To date the several loci involved to the T1DM development have been reliably identified by means of a number of approaches: MHC locus, VNTR within 5'-nontranscibed region of insulin (INS) gene, CTLA4 gene, encoding surface receptor of T cells, PTPN22 and PTPN2 genes, encoding tyrosine phosphatases of T lymphocytes, interleukin 2 (IL2) gene and alpha-chain of its receptor gene (IL2RA), as well as KIAA0350 gene (unknown function) and IFIH1 gene, encoding receptor of double-stranded DNA generated during viral infections. The functional analysis of proteins encoded by the genes, which are involved to the T1DM development, performed to confirm the hypothesis that on the one hand the origin of T1DM development is founded on the some deregulation of mechanisms of the immune tolerance formation and on the other hand the cause is founded on the formation of destructive immune response against own proteins of organism after virus infection or some other immune stress. Thus the protein products of MHC, INS, PTPN22 and PTPN2 genes involve in the formation in thymus of T-lymphocyte repertoire, which provides the immune defense of organism. On the other hand the nonspecific activation of T cells, from that starts the autoimmune destruction of beta-cells of Langerhans islets of pancreas, in all probability, connects with the protein products of CTLA4, IL2, IL2RA genes, and, perhaps, PTPN22 and PTPN2 genes. The only exception, if not considering the genes with unknown function,--is the IFIH1 gene, but its association with T1DM confirms that fact, that the certain types of virus infection can lead to the activation of autoreactive T cells and T1DM development.

Transcranial electrostimulation activates reparative regeneration and the insulin-producing function of pancreatic B-cells in alloxan diabetes in rats

Studies on rats with experimental diabetes induced by administration of alloxan showed that transcranial electrostimulation of endorphinergic brain structures stimulates the regeneration of damaged beta-cells in pancreatic islets of Langerhans. This was identified on pancreatic sections stained with hematoxylin and eosin. De novo formation of small islets was noted, as evidenced by their regeneration from progenitor cells. After transcranial electrostimulation, islet beta-cells stained by the Gomori method showed recovery of granularity - a sign of insulin production. Application of an immunoenzyme method demonstrated recovery of blood insulin levels, the dynamics of increases in which showed a highly significant negative correlation with a decrease in blood glucose. These data led to the conclusion that the antihyperglycemic effect of transcranial electrostimulation in experimental alloxan diabetes results from reparative regeneration of beta-cells in islets of Langerhans with recovery of their insulin-producing function.

Strain Dependent Rat iNOS Promoter Activity—Correlation to Identified WT1 Transcription Factor Binding Site

The free radical nitric oxide (NO) has been implicated in cytokine mediated destruction of rat beta-cells in islets of Langerhans. Cytokine mediated NO production is associated with increased expression of the inducible nitric oxide synthase (iNOS). We have previously shown a strain dependent difference between Wistar Kyoto (WKY) and Brown Norway (BN) rats of IL-1β mediated destruction of islets of Langerhans to be related to expression levels of iNOS and NO production. The aim of the present study was to clone and screen the iNOS gene promoter region from WKY and BN rats for polymorphisms and to functionally test such nucleotide differences. Within the total 2077 bp sequenced from both rat strains we identified three polymorphisms in two separate areas: (i) a GT-repeat polymorphism linked to (ii) a C/T polymorphisms, leading to a WT1 binding site approximately 1650 bp upstream the BN iNOS promoter and (iii) a G/A SNP in exon 1. Apart from these polymorphisms the homology between all published rat iNOS sequences including the presently described are about 96%. Promoter activity was detected for both genes in a luciferase assay followed cloning of 2012 bp fragments and transient transfection into RIN cells. For both strains IL-1β induced dose-dependent activity and strain dependent iNOS promoter activity was demonstrated when WT1 was co-expressed. To our knowledge, this is the first demonstration of functional WT1/iNOS promoter interaction. We conclude that the iNOS promoter is strain-dependently regulated which may relate to quantitatively as well as qualitatively strain dependent differences in transcription factor expression, in this study exemplified by WT1.

Effect of long-term treatment with a purified micronized flavonoid fraction on pancreatic mononuclear cell infiltration in diabetic BB rats.

Bio Breeding (BB) rats develop a genetically determined insulin-dependent diabetes, because of the early destruction of pancreatic beta cells of Langerhans islets, massively infiltrated by inflammatory mononuclear cells. S 5682, registered as Daflon, 500 mg, is a purified micronized flavonoid fraction (90% diosmin, 10% hesperidin), which has been shown to possess antiinflammatory properties, including anti-free radical activity, effects on vascular permeability, venous tone, and perivenous inflammation. We studied the effect of S 5682 on the course of pancreatic insulitis in diabetic BB rats. All the diabetic BB rats were hyperglycemic, with an increase of plasma levels of fructosamine, alpha-1 acid glycoprotein, and fibrinogen, and a dramatic decrease of C-peptide level. These parameters were not modified by S 5682. Pancreas histologic studies showed that in S 5682-treated diabetic BB rats, lymphocytic infiltration of Langerhans islets was less important and frequent than in untreated diabetic BB rats. By quantitative analysis, a highly significant difference was observed for insulitis, as well as perivasculitis, between S 5682-treated and untreated diabetic BB rats. This inhibitory effect of S 5682 on pancreatic mononuclear cell infiltration may be useful for a complementary treatment to decrease the development of insulitis in human insulin-dependent diabetes mellitus.

Prevention of onset in an insulin-dependent diabetes mellitus model, NOD mice, by oral feeding of Lactobacillus casei.

The effect of Lactobacillus casei (LC) on the onset of diabetes in an insulin-dependent diabetes mellitus model, nonobese diabetic (NOD) mice, were examined. From the age of 4 weeks, female NOD mice were fed a diet of either standard laboratory chow (n = 12) or the same chow containing 0.05% weight heat-killed cells of LC (n = 12), and the onset of diabetes was thereafter recorded. The incidence of diabetes in the control group (10/12) was significantly higher than that in the LC-treated group (3/12) (p < 0.01). Pathological analysis in the LC-treated group revealed strong inhibition of the disappearance of insulin-secreting beta cells in Langerhans islets caused by autoimmune disease. The proportion of CD45R+ B-cells in the spleen was increased and that of CD8+ T-cells in spleen cells was decreased in the LC-treated group. Analysis of cytokine production revealed lower interferon-gamma production in the LC-treated group compared to the control group, while the interleukin (IL)-2 production was higher. The levels of IL-4, IL-5, IL-6 and IL-10 in the LC-treated group were somewhat higher than in the control group. Taken together, these findings clearly demonstrated that oral feeding of LC to NOD mice effectively inhibited the occurrence of diabetes and regulated the host immune response.

Single-microelectrode voltage clamp measurements of pancreatic ?-cell membrane ionic currents in situ

A conventional patch clamp amplifier was used to test the feasibility of measuring whole-cell ionic currents under voltage clamp conditions from beta-cells in intact mouse islets of Langerhans perifused with bicarbonate Krebs buffer at 37 degrees C. Cells impaled with a high resistance microelectrode (ca. 0.150 G omega) were identified as beta-cells by the characteristic burst pattern of electrical activity induced by 11 mM glucose. Voltage-dependent outward K+ currents were enhanced by glucose both in the presence and absence of physiological bicarbonate buffer and also by bicarbonate regardless of the presence or absence of glucose. For comparison with the usual patch clamp protocol, similar measurements were made from single rat beta-cells at room temperature; glucose did not enhance the outward currents in these cells. Voltage-dependent inward currents were recorded in the presence of tetraethylammonium (TEA), an effective blocker of the K+ channels known to be present in the beta-cell membrane. Inward currents exhibited a fast component with activation-inactivation kinetics and a delayed component with a rather slow inactivation; inward currents were dependent on Ca2+ in the extracellular solution. These results suggest the presence of either two types of voltage-gated Ca2+ channels or a single type with fast and slow inactivation. We conclude that it is feasible to use a single intracellular microelectrode to measure voltage-gated membrane currents in the beta-cell within the intact islet at 37 degrees C, under conditions that support normal glucose-induced insulin secretion and that glucose enhances an as yet unidentified voltage-dependent outward K+ current.