Number Of Islets Research Articles

Evaluation of Biological Effects of Hydroalcoholic Extract of Hibiscus Rosa Sinensis Flowers on Alloxan Induced Diabetes in Rats.

Aim and Objective The current study sought to investigate antidiabetic, hypolipidimic, antioxidant and histopathological effects of floral extract of Hibiscus rosa sinensis in Alloxan induced Diabetes in rats. Materials and Methods Study was conducted on 6 groups with 6 wistar rats in each group for the period of 4 weeks. Group I: served as normal control (NC), rats administered with gum acacia 1 ml daily, group II: consider as diabetic control (DC) treated with alloxon 150 mg/kg body wt. Whereas Hibiscus rosa-sinensis flower extract was given orally in group III (DE1), group IV (DE2), group V (DE3) at doses of 50, 100 and 200 mg/kg body weight dissolved in distilled water respectively. Group VI (DG) was given glibenclamide (5 mg/kg) as a standard drug and results were compared in reference to it. Results The results indicate that the test compound HEFHR (Hydroalcoholic extract of flower Hibiscus rosa-sinensis) has significant and sustained oral antidiabetic activity, comparable with the hypoglycemic effect of Glibenclamide and Sulphonylurea. Flower extract of HRS was more efficacious in lipid lowering effect and in antioxidative activity than glibenclamide. After 28 day treatment with flower extract, size of islets was significantly increased and necrosis and atrophy of islets were significantly improved; also increase in number and diameter of cell islets appeared to be regular as compared to the diabetic group. Conclusion HEFHR possesses significant antidiabetic, hypolipidemic and antioxidant properties as well as regeneration of beta cells in rats. Further evaluation of HEFHR is in progress.

Increased β-Cell Mass in Obese Rats after Gastric Bypass: A Potential Mechanism for Improving Glycemic Control.

BackgroundOver the past few decades, bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), has become widely considered the most effective treatment for morbid obesity. In most cases, it results in enhanced glucose management in patients with obesity and type 2 diabetes (T2D), which is observed before significant weight loss. However, what accounts for this effect remains controversial. To gain insight into the benefits of RYGB in T2D, we investigated changes in the β-Cell mass of obese rats following RYGB.Material/MethodsRYGB or a sham operation was performed on obese rats that had been fed a high-fat diet (HFD) for 16 weeks. Then, the HFD was continued for 8 weeks in both groups. Additional normal chow diet (NCD) and obese groups were used as controls.ResultsIn the present study, RYGB induced improved glycemic control and enhanced β-Cell function, which was reflected in a better glucose tolerance and a rapidly increased secretion of insulin and C-peptide after glucose administration. Consistently, rats in the RYGB group displayed increased β-Cell mass and islet numbers, which were attributed in part to increased glucagon-like peptide 1 levels following RYGB.ConclusionsOur data indicate that RYGB can improve β-Cell function via increasing β-Cell mass, which plays a key role in improved glycemic control after RYGB.

PTGER4 inhibition in non-obese diabetic mice restores impaired IFNAR signaling, decreases chronic inflammatory signals and inhibits autoimmunity

Abstract We recently demonstrated that dendritic cells (DCs) from autoimmune-prone non-obese diabetic (NOD) mice at prediabetic age (8–10 week) have a diminished IFN-alpha Receptor (IFNAR) response despite increased production of type 1 IFN. This impaired IFN response may result from chronic activation of inflammatory pathways that contribute to dysregulated innate activation. qPCR of innate targets showed that younger NOD mice (3 week old) did not yet display impaired IFNAR signaling, but already had higher IL-1. To understand the interplay between different innate signals, we compared gene expression of 5 key DC populations from prediabetic NOD mice and diabetes-resistant B6.g7 mice. Several inflammatory pathways including IL-1, Eicosanoids, and NFκB were higher in NOD DCs whereas type 1 IFN-response genes, especially those associated with tonic signal, were lower in prediabetic NOD mice. Analysis of potential upstream regulators of these changes identified increased PTGER4 signal and decreased IRF7. PTGER4 binds prostaglandin E2 (PGE2) and mediates specific aspects of both inflammatory and regulatory eicosanoid signaling. Interestingly, NOD mice treated with an inhibitor of PTGER4 displayed increased IFNAR signaling in DCs, but decreased IL-1, Nlrp3 and IFN-gamma production. These changes suggest restoration of cross-talk between key inflammatory mediators, namely that IFN-gamma and IL-1 can inhibit type 1 IFN and vice versa. Furthermore, mice treated with the PTGER4 antagonist display reduced autoimmune pathology, namely an increase in the number and percentage of healthy islets. These findings highlight PTGER4 as a potential target in type 1 diabetes, affecting several inflammatory pathways including IFNAR signaling.

Prolonged Elimination of Negative Feedback Control Mechanisms Along the Insulin Signaling Pathway Impairs β-Cell Function In Vivo

Cellular stress and proinflammatory cytokines induce phosphorylation of insulin receptor substrate (IRS) proteins at Ser sites that inhibit insulin and IGF-I signaling. We therefore examined the effects of mutation of five "inhibitory" Ser phosphorylation sites on IRS2 function in transgenic mice that overexpress, selectively in pancreatic β-cells, either wild-type (WT) or a mutated IRS2 protein (IRS25A). Islets size, number, and mRNA levels of catalase and superoxide dismutase were increased, whereas those of nitric oxide synthase were decreased, in 7- to 10-week-old IRS25A-β mice compared with IRS2WT-β mice. However, glucose homeostasis and insulin secretion in IRS25A-β mice were impaired when compared with IRS2WT-β mice or to nontransgenic mice. This was associated with reduced mRNA levels of Glut2 and islet β-cell transcription factors such as Nkx6.1 and MafA Similarly, components mediating the unfolded protein response were decreased in islets of IRS25A-β mice in accordance with their decreased insulin secretion. The beneficial effects of IRS25A on β-cell proliferation and β-cell transcription factors were evident only in 5- to 8-day-old mice. These findings suggest that elimination of inhibitory Ser phosphorylation sites of IRS2 exerts short-term beneficial effects in vivo; however, their sustained elimination leads to impaired β-cell function.

The effect of G-CSF and AMD3100 on mice treated with streptozotocin: Expansion of alpha-cells and partial islet protection

Administration of streptozotocin (STZ) is one of the most used experimental models of diabetes (STZ-DT). STZ induces beta-cell damage in pancreatic islets. It is known that hematopoietic stem progenitor cells (HSPCs) are mobilized from bone marrow to damaged tissues. In this work, we evaluated the effects of the hematopoietic mobilizers G-CSF (250μg/kg; for five consecutive days) and AMD3100 (5mg/kg; single s.c injection) in mice treated with STZ (175mg/kg). Mice injected with STZ showed a significant reduction in the number and area of islets and in the number of beta- and alpha-cells. Concurrently, they had hyperglycemia (blood glucose over 300mg/dl) associated with very low levels of insulin in plasma. The number and area of islets from STZ-DT mice treated with G-CSF and/or AMD3100 were similar to the controls. However, these mice had neither a reduction of hyperglycemia nor an improvement in the insulin levels. Analysis of islet cellularity showed a large reduction in beta-cells with a significant expansion of alpha-cells. These results indicate that G-CSF and AMD3100 induce partial protection of islet tissues and expansion of alpha-cells in mice treated with STZ but do not protect beta-cells from the damage induced by this compound.

The Efficacy of a Prevascularized, Retrievable Poly(D,L,-lactide-co-ε-caprolactone) Subcutaneous Scaffold as Transplantation Site for Pancreatic Islets.

The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally, this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here, we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) scaffold. Three dosages of rat islets, that is, 400, 800, and 1200, were implanted in immune compromised mice to test the efficacy (n = 5). Islet transplantation under the kidney capsule served as control (n = 5). The efficacy was determined by nonfasting blood glucose measurements and glucose tolerance tests. Transplantation of 800 (n = 5) and 1200 islets (n = 5) into the scaffold reversed diabetes in respectively 80 and 100% of the mice within 6.8 to 18.5 days posttransplant. The marginal dose of 400 islets (n = 5) induced normoglycemia in 20%. The glucose tolerance test showed major improvement of the glucose clearance in the scaffold groups compared to diabetic controls. However, the kidney capsule was slightly more efficacious because all 800 (n = 5) and 1200 islets (n = 5) recipients and 40% of the 400 islets (n = 5) recipients became normoglycemic within 8 days. Removal of the scaffolds or kidney grafts resulted in immediate return to hyperglycemia. Normoglycemia was not achieved with 1200 islets in the unmodified skin group. Our findings demonstrate that the prevascularized poly (D,L-lactide-co-ε-caprolactone) scaffold maintains viability and function of islets in the subcutaneous site.

(−)-Epicatechin-3-O-β-D-allopyranoside from Davallia formosana prevents diabetes and dyslipidemia in streptozotocin-induced diabetic mice

The objective of this study was to evaluate the effects and molecular mechanism of (−)-epicatechin-3-O-β-D-allopyranoside from Davallia formosana (BB) (also known as Gu-Sui-Bu) on type 1 diabetes mellitus and dyslipidemia in streptozotocin (STZ)-induced diabetic mice. This plant was demonstrated to display antioxidant activities and possess polyphenol contents. Diabetic mice were randomly divided into six groups and were given daily oral gavage doses of either BB (at three dosage levels), metformin (Metf) (at 0.3 g/kg body weight), fenofibrate (Feno) (at 0.25 g/kg body weight) or vehicle (distilled water) and a group of control (CON) mice were gavaged with vehicle over a period of 4 weeks. Treatment with BB led to reduced levels of blood glucose, HbA1C, triglycerides and leptin and to increased levels of insulin and adiponectin compared with the vehicle-treated STZ group. The diabetic islets showed retraction from their classic round-shaped as compared with the control islets. The BB-treated groups (at middle and high dosages) showed improvement in islets size and number of Langerhans islet cells. The membrane levels of skeletal muscular glucose transporter 4 (GLUT4) were significantly higher in BB-treated mice. This resulted in a net glucose lowering effect among BB-treated mice. Moreover, BB enhanced the expression of skeletal muscle phospho-AMPK in treated mice. BB-treated mice increased expression of fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor α (PPARα) and mRNA levels of carnitine palmitoyl transferase Ia (CPT1a). These mice also expressed lower levels of lipogenic genes such as fatty acid synthase (FAS), as well as lower mRNA levels of sterol regulatory element binding protein 1c (SREBP1c) and liver adipocyte fatty acid binding protein 2 (aP2). This resulted in a reduction in plasma triglyceride levels. BB-treated mice also expressed lower levels of PPARγ and FAS protein. This led to reduced adipogenesis, fatty acid synthesis and lipid accumulation within adipose tissue, and consequently, to lower triglyceride levels in liver, blood, and adipose tissue. Moreover, BB treatment not only displayed the activation Akt in liver tissue and skeletal muscle, but also in C2C12 myotube to cause an increase in phosphorylation of Akt in the absence of insulin. These results demonstrated that BB act as an activator of AMPK and /or regulation of insulin pathway (Akt), and the antioxidant activity within the pancreas. Therefore, BB treatment ameliorated the diabetic and dyslipidemic state in STZ-induced diabetic mice.

PHARMACOGNOSTIC STANDARDIZATION OF THE LEAF OF MELALEUCA ALTERNIFOLIA (MAIDEN & BETCHE) CHEEL.

Background:Melaleuca alternifolia (Myrtaceae) is a well-known, commonly used, tall shrub plant in Ayurvedic medicine. Traditionally, it is used for its antimicrobial potential to treat cutaneous infections. No attempts have been made regarding pharmacognostic investigation of the plant till date. So, the present study was aimed to establish standards with the help of different pharmacognostic parameters.Methods:Various pharmacognostic parameters (morphological, microscopic, physicochemical evaluations and preliminary phytochemical screening) were studied along with fluorescent and thin layer chromatographic analysis of the extract.Result:Morphologically Melaleuca alternifolia is a shrub having height of 7 m with layered and papery bark. Leaves have an arranged pattern, petiole is 1 mm in length; linear-acute with dimensions of 10-35 mm x 1 mm. Organoleptic features shows that leaves have characteristic odour and astringent taste. The transverse section of the leaf reveals the existence of epidermal layers, mesophyll tissues, vascular bundles and secretory cavities. The stomata are anomocytic and leaf constants such as stomatal number is 180-200-225, stomatal index is 3.8-4.4-5.9, vein islet number is 18.68 (average), veinlet termination number 20.3 (average) and palisade ratio is 5.5-6.4-6.9. The results of phytochemical screening showed the occurrence of different phytoconstituents (flavonoids, phenolic tannins, phytosterol and terpenoids).Conclusion:The present study evaluated various pharmacognostic parameters which will help in quality control (standardization) of Melaleuca alternifolia leaves in crude form, in herbal formulation and also aid in the preparation of an herbal monograph for the species.

The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.

Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP). The marginal number of islets by PV, KC, or SP was 200, 100, and 50, respectively. Some plasma inflammatory cytokine levels in the SP group were significantly lower than those of the PV group after receiving a marginal number of islets, indicating reduced inflammation in the SP group. Insulin contents were increased 280 days after islet transplantation compared with those immediately following transplantation (p<0.05). Additionally, Tlx1-related genes, including Rrm2b and Pla2g2d, were up-regulated, which indicates that islet grafts expanded in the spleen. The spleen is an ideal candidate for an alternative islet transplantation site because of the resulting reduced inflammation and expansion of the islet graft.

Interspecies organogenesis generates autologous functional islets.

Islet transplantation is an established therapy for diabetes. We have previously shown that rat pancreata can be created from rat pluripotent stem cells (PSCs) in mice through interspecies blastocyst complementation. Although they were functional and composed of rat-derived cells, the resulting pancreata were of mouse size, rendering them insufficient for isolating the numbers of islets required to treat diabetes in a rat model. Here, by performing the reverse experiment, injecting mouse PSCs into Pdx-1-deficient rat blastocysts, we generated rat-sized pancreata composed of mouse-PSC-derived cells. Islets subsequently prepared from these mouse-rat chimaeric pancreata were transplanted into mice with streptozotocin-induced diabetes. The transplanted islets successfully normalized and maintained host blood glucose levels for over 370 days in the absence of immunosuppression (excluding the first 5 days after transplant). These data provide proof-of-principle evidence for the therapeutic potential of PSC-derived islets generated by blastocyst complementation in a xenogeneic host.

Influence of feeding habits in the endocrine pancreas of insectivore bat Pteronotus personatus and nectarivore bat Anoura geoffroyi: A comparative stereological and immunohistochemical study.

Pteronotus personatus as an insectivore bat and has a diet that consists of a high protein diet, whereas the diet of Anoura geoffroyi, a predominantly nectarivore bat, is rich in simple sugars like sucrose, glucose and fructose. Considering that diet influences the activation of different pathways, which may influence morphological adaptations in the gastrointestinal system, the aim of this study was to compare the morphology of the endocrine pancreas in P. personatus and A. geoffroyi. For this, histological, stereological and immunohistochemical methods were used. In P. personatus, the average diameter of the pancreatic islet was 40.47μm±13.94, while in A. geoffroyi was 88.16μm±36.40. The total number of pancreatic islets in P. personatus was 26150±2346 and in A. geoffroyi was 15970±1666. In P. personatus, the volume density of the pancreatic islets was 3.4%± 2.6, whereas in A. geoffroyi the volume density was 6.1%±3.7. In addition, the immunodensity of the α, β and δ cells, in P. personatus was 25.8%±11.9, 35.5%±13.5, 3.9%±0.7, respectively, and in A. geoffroyi was 33.10%±12.7, 55.08%±7.4, 6.2%±4.6, respectively. In conclusion, the results of this study indicate differences in the pancreatic weight/body, weight ratio, diameter and volume density of pancreatic islets and in immunodensity of the β and α cells between both species, which have different dietary habits.

Shoreline changes in reef islands of the Central Pacific: Takapoto Atoll, Northern Tuamotu, French Polynesia

Atoll reef islands are considered highly vulnerable to the impacts of climate change. While accelerated sea-level rise is expected to destabilize reef islands, ocean warming and acidification are considered as major threats to coral reef growth, which is of primary importance for the persistence of islands and of food supply to islanders. Using multi-date aerial imagery, shoreline and island changes between 1969 and 2013 were assessed on Takapoto Atoll, Northern Tuamotu region, in French Polynesia. Results show that over the 44-year study period, 41% of islands were stable in area while 33% expanded and 26% contracted. Island expansion was the dominant mode of change on the leeward side of the atoll. Tropical Cyclone Orama (category 3, 1983) contributed to shoreline and island change on the windward side of the atoll through the reworking of previous storm deposits and the injection of fresh sediments in the island system (with up to 62% of an island's land area being covered with fresh sediments). Human activities contributed significantly to shoreline and island change throughout the atoll through infrastructure construction, the removal of the indigenous vegetation from a number of islets and sediment mining.

Effective Isolation of Functional Islets from Neonatal Mouse Pancreas.

Perfusion-based islet-isolation protocols from large mammalian pancreata are well established. Such protocols are readily conducted in many laboratories due to the large size of the pancreatic duct that allows for ready collagenase injection and subsequent tissue perfusion. In contrast, islet isolation from small pancreata, like that of neonatal mice, is challenging because perfusion is not readily achievable in the small pancreata. Here we describe a detailed simple procedure that recovers substantial numbers of islets from newly born mice with visual assistance. Freshly dissected whole pancreata were digested with 0.5 mg/mL collagenase IV dissolved in Hanks' Balanced Salt Solution (HBSS) at 37 °C, in microcentrifuge tubes. Tubes were tapped regularly to aid tissue dispersal. When most of the tissue was dispersed to small clusters around 1 mm, lysates were washed three to four times with culture media with 10% fetal bovine serum (FBS). Islet clusters, devoid of recognizable acinar tissues, can then be recovered under dissecting stereoscope. This method recovers 20 - 80 small- to large-sized islets per pancreas of newly born mouse. These islets are suitable for most conceivable downstream assays, including insulin secretion, gene expression, and culture. An example of insulin secretion assay is presented to validate the isolation process. The genetic background and degree of digestion are the largest factors determining the yield. Freshly made collagenase solution with high activity is preferred, as it aids in endocrine-exocrine isolation. The presence of cations [calcium (Ca2+) and magnesium (Mg2+)] in all solutions and fetal bovine serum in the wash/picking media are necessary for good yield of islets with proper integrity. A dissecting scope with good contrast and magnification will also help.

Improvement of Insulin Secretion and Pancreatic β-cell Function in Streptozotocin-induced Diabetic Rats Treated with Aloe vera Extract.

Background:Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. Plant extracts and their products are being used as an alternative system of medicine for the treatment of diabetes. Aloe vera has been traditionally used to treat several diseases and it exhibits antioxidant, anti-inflammatory, and wound-healing effects. Streptozotocin (STZ)-induced Wistar diabetic rats were used in this study to understand the potential protective effect of A. vera extract on the pancreatic islets.Objective:The aim of the present study was to evaluate the A. vera extract on improvement of insulin secretion and pancreatic β-cell function by morphometric analysis of pancreatic islets in STZ-induced diabetic Wistar rats.Materials and Methods:After acclimatization, male Wistar rats, maintained as per the Committee for the Purpose of Control and Supervision of Experiments on Animals guidelines, were randomly divided into four groups of six rats each. Fasting plasma glucose and insulin levels were assessed. The effect of A. vera extract in STZ-induced diabetic rats on the pancreatic islets by morphometric analysis was evaluated.Results:Oral administration of A. vera extract (300 mg/kg) daily to diabetic rats for 3 weeks showed restoration of blood glucose levels to normal levels with a concomitant increase in insulin levels upon feeding with A. vera extract in STZ-induced diabetic rats. Morphometric analysis of pancreatic sections revealed quantitative and qualitative gain in terms of number, diameter, volume, and area of the pancreatic islets of diabetic rats treated with A. vera extract when compared to the untreated diabetic rats.Conclusion:A. vera extract exerts antidiabetic effects by improving insulin secretion and pancreatic β-cell function by restoring pancreatic islet mass in STZ-induced diabetic Wistar rats.SUMMARY Fasting plasma glucose (FPG) and insulin levels were restored to normal levels in diabetic rats treated with Aloe vera extractIslets of pancreas were qualitatively and quantitatively restored to normalcy leading to restoration of FPG and insulin levels of diabetic rats treated with Aloe vera extractMorphometric analysis of pancreatic sections revealed quantitative and qualitative gain in terms of number, diameter, volume, and area of the pancreatic islets of diabetic rats treated with Aloe vera extract when compared to the untreated diabetic rats. Abbreviations Used: A. vera, FPG: Fasting plasma glucose, STZ: Streptozotocin, BW: Body weight

Role of Natural Killer Cells in the Innate Immune System After Intraportal Islet Transplantation in Mice

BackgroundBoth liver natural killer (NK) and NK T cells of the innate immune system play a crucial role in islet graft loss after intraportal islet transplantation, although a relationship between NK and NK T cells in islet loss has not been proven. In this study, we investigated the role of NK cells in the innate immune system in islet graft loss after intraportal islet transplantation. MethodsTo investigate the involvement of liver NK cells in islet destruction, we assessed the differences in graft survival after intraportal islet transplantation between CD1d−/− diabetic mice and NK cell–depleted CD1d−/− diabetic mice. ResultsThe transplantation of 400 islets into the liver was sufficient to reverse hyperglycemia in wild-type diabetic mice (100%, 4/4). However, normoglycemia could not be achieved when 200 islets were transplanted (0%, 0/4). In contrast, intraportal transplantation of 200 islets in NK cell–depleted CD1d−/− diabetic mice ameliorated hyperglycemia in 71% of cases (5/7), whereas transplantation of the same number of islets in CD1d−/− diabetic mice did not (0%, 0/4). Histologic findings also confirmed that intact islets were observed in NK cell–depleted CD1d−/− diabetic mice, but were difficult to observe in CD1d−/− diabetic mice. ConclusionsThe involvement of liver NK cells in the innate immune system related to islet graft loss after intraportal islet transplantation is revealed by improved graft survival and function in NK cell–depleted CD1d−/− diabetic mice. Our data reveal that regulation of NK cell activity is particularly important when insufficient islet numbers are used for transplantation.

Benefits of Islet Transplantation as an Alternative to Pancreas Transplantation: Retrospective Study of More Than 10 Ten Years of Experience in a Single Center.

Pancreas transplantation (PTx) represents the method of choice in type 1 diabetic patients with conservatively intractable hypoglycemia unawareness syndrome. In 2005, the Institute for Clinical and Experimental Medicine (IKEM) launched a program to investigate the safety potential of islet transplantation (ITx) in comparison to PTx. This study aims to compare the results of PTx and ITx regarding severe hypoglycemia elimination, metabolic control, and complication rate. We analyzed the results of 30 patients undergoing ITx and 49 patients treated with PTx. All patients were C-peptide-negative and suffered from hypoglycemia unawareness syndrome. Patients in the ITx group received a mean number of 12,349 (6,387-15,331) IEQ/kg/person administered percutaneously into the portal vein under local anesthesia and radiological control. The islet number was reached by 1-3 applications, as needed. In both groups, we evaluated glycated hemoglobin, insulin dose, fasting and stimulated C-peptide, frequency of severe hypoglycemia, and complications. We used the Mann Whitney test, Wilcoxon signed-rank test, and paired t-test for analysis. We also individually assessed the ITx outcomes for each patient according to recently suggested criteria established at the EPITA meeting in Igls. Most of the recipients showed a significant improvement in metabolic control one and two years after ITx, with a significant decrease in HbA1c, significant elevation of fasting and stimulated C-peptide, and a markedly significant reduction in insulin dose and the frequency of severe hypoglycemia. Seventeen percent of ITx recipients were temporarily insulin-independent. The results in the PTx group were comparable to those in the ITx group, with 73% graft survival and insulin independence in year 1, 68% 2 years and 55% 5 years after transplantation. There was a higher rate of complications related to the procedure in the PTx group. Severe hypoglycemia was eliminated in the majority of both ITx and PTx recipients. This report proves the successful initiation of pancreatic islet transplantation in a center with a well-established PTx program. ITx has been shown to be the method of choice for hypoglycemia unawareness syndrome, and may be considered for application in clinical practice if conservative options are exhausted.

Effect of Platelet Rich Plasma (PRP) Injection on the Endocrine Pancreas of the Experimentally Induced Diabetes in Male Albino Rats: A Histological and Immunohistochemical Study

Introduction: Diabetes mellitus is a global problem and several restoration approaches have been developed to induce beta (β) cells regeneration. Platelet rich plasma (PRP) is an autogenous and economical source of growth factors which nowadays used in the tissue repair. Aim: To test the hypothesis that PRP could play a role in the improvement of the structural changes occurred in the endocrine pancreas of experimentally- induced diabetic rats and the possible mechanisms through which PRP induced its effects to shed a light on the possible use of such application in the clinical field. Material and methods: Sixty male albino rats were used; 20 for obtaining the PRP and 40 were divided into 4 equal groups (10 rats each): control, PRP-group, diabetic group, PRP/diabetic group. Diabetes was induced by single intra-peritoneal injection of streptozotocin (50-60 mg/kg). The PRP was administered by SC injections in a dose of 0.5 mg/kg twice weekly for 3 weeks. Results: The diabetic group showed a significant increase in blood glucose levels compared to the control. Treatment with PRP significantly reduced the blood glucose levels compared to the diabetic group. The diabetic group showed variable marked morphological changes which diminished by the PRP administration. PRP/diabetic group had a significant increase in the mean number of pancreatic islets and β-cells/islet compared to the diabetic group. The islet cells appeared normal with scarcely seen vacuolations. The duct system showed several changes; stratifications, invagination of the surface epithelium to the underlying connective tissue, and sprouting of the ductal epithelial cells in between the lobules. Numerous small islets were noticed in a close association with the intralobular ducts. Small newly lobules with abundant connective tissue were organized. There were significant increases in the insulin immunopositive β-cells and PCNA positive cells in PRP/diabetic group compared to diabetic group. Conclusion: This study provides an evidence of the diabetic pancreatic islet regeneration in response to PRP treatment. The PRP stimulated islet cell regeneration and stimulated the induction of other sources of β-cells generation as the exocrine portion of the pancreas; ductal and acinar cells. In addition, PRP might put the pancreas into an environment similar to the postnatal developmental one where new lobules were formed. These will pave the future for a novel treatment for diabetes.

EFFECT OF ETHYLMETHYLHYDROXYPYRIDINE MALATE ON THE ABSOLUTE NUMBERS OF ERYTHROBLASTIC ISLETS IN RATS EXPOSED TO SULFUR-CONTANING GAS AT DIFFERENT STAGES OF POSTNATAL ONTOGENESIS

Objective . To study the effect of the protective agent ethylmethylhydroxypyridine malate on the numbers of erythroblastic islets in rats exposed to sulfur-containing gases. Materials and methods . Natural sulfur-containing gas mixtures from the Astrakhan gas-condensate field were used to model the gas-polluted environment. Male rats of various ages simulated different stages of postnatal human ontogenesis. Results . The obtained results indicate that at all stages of ontogenesis ethylmethylhydroxypyridine malate protected erythroblastic islets from intoxication by gaseous sulfur pollutants and led to partial normalization of proliferation and maturation of eryth rob lasts. Conclusion . The protective action of ethylmethylhydroxypyridine malate may be used for neutralizing the biological damage caused by toxic air pollutants at different stages of ontogenesis.

Salutary Effects of Germinated Glycine max Seeds on Post Prandial Hyperglycemia and Dyslipidemia - Evidence from In-vivo and In-vitro Studies

Background: Germinated Glycine max seeds have been known to have anti-hyperglycemic effects; however, a comprehensive study pertaining to this has never been experimentally determined. Methods: The aqueous extract of 12 h germinated Glycine max seeds (gGmax) were orally administered to Streptozotocin induced diabetic rats for 28 days and the effects were observed on glycemic index, lipid profile, antioxidant parameters alpha amylase and alpha glucosidase activity. Further the histomorphological changes were seen in the rat’s pancreas. Finally, the metabolite profiling was done. Results: There was a significant improvement in FBG and OGTT in diabetic rats treated with gGmax after a period of 28 days. The extract also led to a substantial increase in the levels of insulin and c-peptide as compared to diabetic control rats with marked improvement in insulin resistance. Lipid profile and atherogenic factors were significantly improved. Histomorphological examination of pancreatic tissue revealed increased number of islets and β-cells in treated rats as compared to diabetic controls. Subsequently, marked suppression in the activity of alphaamylase and alpha- glucosidase was observed. Conclusion: The antidiabetic property of the extract is attributed through the improvement in insulin secretion, suppression of post- prandial hyperglycemia and β-cell regeneration. Besides its antidiabetic properties, Glycine max seeds also demonstrated salutary effects on the management of dyslipidemia which may be mediated through scavenging of free radicals as well as suppression of atherogenic lipid variants and apolipoproteins. Overall this study represents Glycine max seeds as a promising therapeutic agent for diabetes and dyslipidemia.

Improved insulin-secreting properties of pancreatic islet mesenchymal stem cells by constitutive expression of Pax4 and MafA.

For long-term treatment of diabetes type 1, transplantation of insulin-producing beta cells may be a promising method, but the limited number of islets for transplantation requires the development of different approaches. In this study, we aimed to generate betalike insulin-producing cells. For this purpose, MafA, Pax4, and Ngn3 genes were transferred into pancreatic islet-derived mesenchymal stem cells, and the effect of their ectopic expressions on differentiation efficiency was examined. Stemness properties of pancreatic islet stem cells were characterized. The 3 genes were transfected by electroporation and expressed constitutively. The transfected cells were further stimulated to differentiate by using chemical induction. Pax4 expression had significant effects on differentiation into insulin-producing cells. Although it caused morphological alterations in cells, similar to epithelial cells, the insulin secretion levels remained lower than those of the cell line cotransfected with MafA and Pax4. Cotransfection of the 3 transcription factors did not further improve the beta-like cell generation. MafA and Pax4 ectopic expression resulted in improved differentiation efficiency into insulin-secreting cells. However, support of this differentiation process using additional chemical induction may sufice to overcome control by endogenous regulatory pathways.