Islets Of Langerhans In Pancreas Research Articles

Co-treatment with grape seed extract and mesenchymal stem cells in vivo regenerated beta cells of islets of Langerhans in pancreas of type I-induced diabetic rats

BackgroundNowadays, diabetes mellitus is known as a silent killer because individual is not aware that he has the disease till the development of its complications. Many researchers have studied the use of stem cells in treatment of both types of diabetes. Mesenchymal stem cells (MSCs) hold a lot of potential for regenerative therapy. MSCs migrate and home at the damaged site, where they can aid in the repair of damaged tissues and restoring their function. Oxidative stress and inflammation represent a huge obstacle during MSCs transplantation. Therefore, the present study aimed to evaluate the role of grape seed extract (GSE) administration during MSCs transplantation in streptozotocin (STZ)-induced type I diabetes. Furthermore, testing some of GSE components [procyanidins(P)-B1 and P-C1] in conjunction with MSCs, in vivo, was performed to determine if one of them was more effective in relieving the measured attributes of diabetes more than the whole GSE.MethodsFirstly, GSE was prepared from the seeds of Muscat of Alexandria grapes and characterized to identify its phytochemical components. Experimental design was composed of control group I, untreated diabetic group II, GSE (300 mg/kg)-treated diabetic group III, MSCs (2 × 106 cells/rat)-treated diabetic group IV and GSE (300 mg/kg)/MSCs (2 × 106 cells/rat)-treated diabetic group V. Type I diabetes was induced in rats by intravenous injection with 65 mg/kg of STZ. Treatment started when fasting blood glucose (FBG) level was more than 200 mg/dl; GSE oral administration started in the same day after MSCs intravenous injection and continued daily for 30 consecutive days.ResultsThe results showed that GSE/MSCs therapy in type I-induced diabetic rats has dramatically managed homeostasis of glucose and insulin secretion; together with, improvement in levels of inflammatory markers and oxidative stress.ConclusionCo-treatment with GSE and MSCs in vivo regenerates beta cells in type I-induced diabetic rats.

Morphological analysis of isolated rat pancreatic islets cultured under standard culture technique and with biopolymer microstructured collagen‑containing hydrogel

Introduction. Extracellular matrix play an essential role in providing structural integrity and physiological support to Langerhans islets in pancreas. Imitation of the native microenvironment can be useful for viability of isolated pancreatic islets in vitro and in vivo. Aim. The purpose of this study was to characterize and compare the effect of biopolymer microstructured collagen-containing hydrogel (BMCH) on isolated rat islets survival. Materials and methods. Islets were isolated by classic collagenase techniques with some modifications. There were used hystological, immunofluorescence and immunohystochemistry methods. Results. Rat islets cultured with collagen-based gel don’t revealed destructive changes of structure and remained viabile 7 days incubation. Conclusion. Positive effect of BMCH to rat islet survival was revealed.

Insulin hormone: Mechanism and effects on the body and relationship with central nervous system

Diabetes Mellitus (DM) dunyadaki en yaygin kronik hastaliklardan biridir. Ya yetersiz insulin salinmasi ya da insuline karsi olusan direnc ile karakterizedir. Insulin pankreasin Langerhans adaciklarindaki beta hucrelerinden salinan ve vucuttaki karbonhidrat metabolizmasinin duzenlenmesinde glukagon ile birlikte rol alan bir hormondur. Insulinin, karbonhidratlar uzerindeki etkileri baglaminda, insulin hemen hemen tum dokularda (beyin haric), glikozun hucrelere kolaylastirilmis difuzyonunu hizlandirmakta ve kan glikoz duzeyini azaltmaya yonelik bir etki olusturmaktadir. Bir baska ifadeyle insulin kan seker duzeyinin duzenlenmesinde gorev alir. Insulin sekresyonunun enerji miktarindaki artisla alakali oldugu bilinmektedir. Hucre ici enzimlerle yakindan iliskili olup, insulinin, glikolitik ozellige sahip; glukokinaz, piruvat kinaz, fosfofrukto kinaz ve fruktoz 2,6 bifosfataz uzerinde transkripsiyonu stimule edici etkisi oldugu, glukoneogenik ozellikli fosfofenolpurivat karboksikinaz uzerinde transkripsiyonu inhibe edici etkiye sahip oldugu gosterilmistir. Insulinin, karbonhidrat metabolizmasinin birincil dengeleyicisi olmasinin yaninda, karbonhidrat metabolizmasi ile iliski icinde bulunan yag ve protein metabolizmalari uzerinde de onemli etkileri vardir. Diyabetin Merkezi Sinir Sistemi (MSS) uzerindeki etkilerinin temelinde ise iki mekanizmanin onemi uzerinde durulmakta, bunlardan ilkinin metabolik degisiklikler sonucu ortaya cikan oksidatif stres oldugu, digerinin ise kalsiyum iyonu metabolizmasinda meydana gelen bozukluklardan kaynaklandigi iddia edilmektedir. Bu derlemede insulinin temel etki mekanizmalari, hucresel duzeydeki yansimalari ve MSS ile olan iliskisi uzerinde durularak detayli bilgiye ulasilmasi amaclanmistir.

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.

Hepatocyte Growth Factor Preserves Beta Cell Mass and Mitigates Hyperglycemia in Streptozotocin-induced Diabetic Mice

Type I diabetes is an autoimmune disease that results in destructive depletion of the insulin-producing beta cells in the islets of Langerhans in pancreas. With the knowledge that hepatocyte growth factor (HGF) is a potent survival factor for a wide variety of cells, we hypothesized that supplementation of HGF may provide a novel strategy for protecting pancreatic beta cells from destructive death and for preserving insulin production. In this study, we demonstrate that expression of the exogenous HGF gene preserved insulin excretion and mitigated hyperglycemia of diabetic mice induced by streptozotocin. Blood glucose levels were significantly reduced in mice receiving a single intravenous injection of naked HGF gene at various time points after streptozotocin administration. Consistently, HGF concomitantly increased serum insulin levels in diabetic mice. Immunohistochemical staining revealed a marked preservation of insulin-producing beta cells by HGF in the pancreatic islets of the diabetic mice. This beneficial effect of HGF was apparently mediated by both protection of beta cells from death and promotion of their proliferation. Delivery of HGF gene in vivo induced pro-survival Akt kinase activation and Bcl-xL expression in the pancreatic islets of diabetic mice. These findings suggest that supplementation of HGF to prevent beta cells from destructive depletion and to promote their proliferation might be an effective strategy for ameliorating type I diabetes.

EC3, a Heterodimeric Disintegrin from Echis carinatus, Inhibits Human and Murine α4 Integrin and Attenuates Lymphocyte Infiltration of Langerhans Islets in Pancreas and Salivary Glands in Nonobese Diabetic Mice

The venom of Echis carinatus suchoreki contains a monomeric disintegrin echistatin (Mr 5,500 Da) that strongly inhibits αIIbβ3, αvβ3, and α5β1 integrins and a heterodimeric disintegrin called EC3 (Mr 14,762 Da). At nanomolar concentration, EC3 inhibits adhesion of human cell lines expressing α4β1 and α4β7 to immobilized VCAM-1; it has a lower inhibitory effect on α5β1-mediated cell adhesion. In this study, we demonstrated that EC3, in contrast to echistatin, inhibited binding of monoclonal anti-α4 and anti-α5 antibodies to cells expressing α4β7. In a dose-dependent manner and to the same extent, EC3 inhibited adhesion of Jurkat cells and murine splenic lymphocytes to immobilized VCAM-1, whereas echistatin was not active. EC3 injected intraperitoneally into nonobese diabetic (NOD mice) suppressed development of insulitis and sialoadenitis, whereas echistatin had no significant effect. We propose that the effect of EC3 is mediated, at least, in part, by blocking α4β1 and α4β7 on murine lymphocytes.

How and why do neurons generate complex rhythms with various frequencies?

Some neurons generate endogenous rhythms with a period of a few hundred milliseconds,while others generate rhythms with a period of a few tens of seconds. Sometimes rhythms appear chaotic. Explaining how these neurons can generate various modes of oscillation with a widely ranging frequency is a challenge. In the first part of this review, we illustrate that such rhythms can be generated from simple yet elegant mathematical models. Chaos embedded in rhythmic activity has interesting characteristics that are not seen in other physical systems. Understanding of how these neurons utilizes endogenous rhythms to communicate with each other is important in elucidating where the brain gets various rhythms and why it can pervert into abnormal rhythms under diseased conditions. Using the islet of Langerhans in pancreas as an example, in the second part of this review, we illustrate how insulin secreting β‐cells communicate with glucagon secreting α‐cells to achieve an optimal insulin release.

A high-molecular IGF-2 immunoreactive peptide (pro-IGF-2?) in the insulin cells of the islets of Langerhans in pancreas of man and rat

Histopathologically normal pancreatic parenchyma from 12 adult men and women, as well as that from 14 adult rats (Sprague-Dawley and Wistar strains), were investigated immunohistochemically with a mouse monoclonal antibody, raised against recombinant human pro-IGF-2. The antiserum showed no crossreactivity with insulin; IGF-1 had 0.1% of the reactivity of IGF-2. The immunohistochemical observations were checked by means of a radioimmunoassay (RIA), based on the same antibody, of an extract of a sample of one of the human pancreatic glands. Analogous investigations for insulin were made in parallel, using polyclonal insulin antisera. A high-molecular (12 kDa) IGF-2-like peptide was found in the islets of Langerhans, being localized to the insulin cells. These cells were identified as β-cells by immunohistochemistry with insulin antisera on adjacent paraffin sections. From observations made by means of acid-gel-chromatography, the peptide was tentatively supposed to represent either pro-IGF-2, or a partially processed form of it.

A study of caerulein action on secretory cells, especially in the islets of Langerhans in the rat pancreas (author's transl)

Although it is known that caerulein exerts an action on the secretory activity of the islets of Langerhans in the pancreas, the mechanism of this hormone has not yet been ascertained. The present investigation was undertaken to observe the ultramicroscopic changes of the pancreatic islets and the peripheral blood levels of insulin, glucagon, glucose and electrolites after caerulein administration. The animals were divided into four groups, and three were injected intraperitoneally with caerulein at 25 micrograms/kg, 2 micrograms/kg and 0.2 microgram/kg body weight, respectively. The fourth group served as the control. In the first group (25 micrograms caerulein), the endocrine cells of the pancreatic islets showed accelerated functioning immediately and up to about 2 hours after injection. Then these cells degenerated due to cytoplasmic edema and evidenced decreased secretory activity. In the second group (2 micrograms) depression in the secretory activity occurred for about 2 hours immediately after the injection, but there was no destruction of cells and they gradually recovered their functioning. The third group (0.2 microgram) displayed an acceleration of secretory activity immediately after the injection and then recovered to the normal state. There were some changes of electrolites in the peripheral blood in each of the three groups, suggesting that caerulein causes acceleration and depression of the secretory activities in the islets of Langerhans in the pancreas depending on the dosage. Moreover, the cell alterations may well depend on the changes of electrolites in the inner and outer atmospheres of the cells.

The Scrapie Agent

Hamsters injected intracerebrally with scrapie strains 139H or 263K or with normal hamster brain were assessed for body weight periodically throughout the incubation period. Animals injected with the 139H scrapie strains became obese(92 days) before the appearance of the neuromotor changes that are indicative the start of clinical disease(130 days). During the latter part of the incubation period, 139H injected hamsters showed marked hyperlipidemia. In group of obese hamster, total lipid, phospholipid and NEFA levels in serum significantly increased. At autopsy, there was marked hyperplasia and hypertrophy of the cells of the islets of Langerhans in pancreas. Liver and kidney also were enlarged. However animal injected with the 263K scrapie strain did not developed obese and hyperlipidemia. This system has value as a experi- mental animal models for research of obese with hyperlidemia syndromes in human.