Survival Of Pancreatic Islets Research Articles

Combined therapy with interleukin-4 and interleukin-10 inhibits autoimmune diabetes recurrence in syngeneic islet-transplanted nonobese diabetic mice. Analysis of cytokine mRNA expression in the graft.

Syngeneic pancreatic islet grafts in nonobese diabetic (NOD) mice elicit a cell-mediated autoimmune response that destroys the insulin-producing beta cells in the islet graft. IL-4 and IL-10 are cytokines that inhibit cell-mediated immunity. In this study, we evaluated the effects of IL-4 and IL-10 on the survival of syngeneic pancreatic islets transplanted into diabetic NOD mice. Islet grafts survived beyond 18 days and normoglycemia was maintained in 67% (10 of 15) of mice treated with IL-4 plus IL-10, but in none (0 of 20) of vehicle-injected (control) mice. Also, 40% (6 of 15) of the mice treated with IL-4 plus IL-10 were normoglycemic at 30 days after transplantation, compared with 14% (1 of 7) of the mice treated with IL-4 alone, 8% (1 of 13) of the mice treated with IL-10 alone, and none (0 of 20) of the control mice. Histological examination of grafts at 10 days after transplantation revealed peri-islet accumulations of mononuclear leukocytes and intact islet beta cells in grafts from IL-4 plus IL-10-treated mice, whereas islets were infiltrated by leukocytes and the beta cell mass was greatly reduced in grafts from control mice. Polymerase chain reaction (PCR) analysis of cytokine mRNA expression in the grafts revealed higher levels of IL-2, IFN gamma, and IL-10 mRNA in grafts of diabetic compared with normoglycemic control mice, whereas IFN gamma and TNF alpha mRNA levels were significantly decreased in grafts of IL-4 plus IL-10-treated mice compared with either normoglycemic or diabetic control mice. These results suggest that T helper (Th)1 cells and their cytokine products (IL-2, IFN gamma, and TNF alpha) may promote islet beta cell destructive insulitis and autoimmune diabetes recurrence in syngeneic islet-transplanted NOD mice, and that administration of IL-4 plus IL-10 may inhibit diabetes recurrence by suppressing Th1 cytokine production in the islet grafts.

The Effect of Human Amniotic Fluid in Supporting Long-Term Survival of Pancreatic Islets in Tissue Culture

Pancreatic islets obtained from newborn Lewis rats were kept free-floating in TCM 199 either in the presence of 50% human amniotic fluid (HAF), 50% Hank's balanced salt solution (HBSS) or 10% fetal calf serum (FCS) for up to 14 days. The culture, in the presence of HAF, resulted in a good islet viability as demonstrated by islet number, islet insulin content and insulin release into the medium. Contradictory results were obtained when HBSS was used as the medium supplement. Moreover, the islets cultured in HAF-supplemented medium are characterized by a marked replicatory activity as reflected by the incorporation of labeled thymidine into islet DNA and gradual increase in DNA content with the progression of culture time. Even if compared to DNA synthesis of islets cultured under so called standard culture conditions as e.g. supplementation of 10% FCS to the medium, 50% HAF but not yet 10% HAF was found to stimulate the islet replication twofold already after 4 days of culture. It was also demonstrated that FCS has no additional effect on HAF-stimulated DNA synthesis. These findings support the view that HAF-enriched culture medium may have a use in supporting the long-term survival of well preserved endocrine pancreatic tissue.

Effects of ganglioside (Cronassial) treatment on MHC Ia antigen expression and allograft survival of pancreatic islets in diabetic rats

Streptozotocin-diabetic BdII rats were treated daily with 20 mg/kg body weight gangliosides for ten days beginning two days before transplantation. This treatment did not prolong allograft survival of untreated Lewis islets. Culture treatment of isolated Lewis islets with gangliosides (100 micrograms/ml in RPMI 1640) for one day resulted in a significant reduction of MHC Ia antigen positive cells but not of class I antigens within the islets. Transplantation of the ganglioside pretreated islets into non-immunosuppressed BdII recipients prolonged allograft survival to 12 days only in one of five animals.

Functional characteristics of cultured mouse pancreatic islets following exposure to different streptozotocin concentrations

The present study was undertaken to investigate the acute and long-term effects of streptozotocin (SZ) on pancreatic islet function and survival in vitro. Isolated mouse pancreatic islets, that had been cultured overnight, were exposed to SZ (0.55–4.4 mM) or critic acid buffer in the case of the control group. The islets were examined either immediately after SZ exposure or after one week in culture. There was a marked loss of islets treated with 2.2 and 4.4 mM SZ during the culture; however, the DNA content of the remaining islets was unaffected. The islet insulin content was reduced 7 days after treatment with 2.2 and 4.4 mM SZ. At 4.4 mM the glucagon and somatostatin content of the islet was also decreased but not to the same degree as the insulin content. SZ-induced inhibition of glucose-stimulated insulin release and (pro)insulin biosynthesis was more pronounced on day 7 as compared to day 0. A similar pattern of inhibitory action of SZ was observed on islet glucose oxidation rates. Islet ATP contents were depressed on day 7 in islets exposed 4.4 mM SZ, but were otherwise similar to the control group. Islet NAD + NADH contents were decreased by 50% after exposure to 2.2 mM SZ, compared to the control islets on day 0. This decrease in NAD + NADH contents was to a large extent restored during the one-week culture. The present study shows that islets failed to completely repair the acute damage caused by SZ, and that the impairment of the islet glucose-stimulated insulin release induced by SZ seemed to progress in culture. This lasting cytotoxic effect may reflect a sustained inhibitory action of SZ on the glucose metabolism of the B-cells, which specifically affects the insulin production of the cells.

Function of lymphocytes and macrophages after cryopreservation by procedures for pancreatic islets: Potential for reducing tissue immunogenicity

The survival of tissue allografts can be extended by pretreating the tissue to remove the stimulatory leucocytes that populate the graft; with this in mind, we have recently begun to explore a cryobiological approach to modulating tissue immunogenicity by using the differential susceptibility of different cells to freezing injury. The sensitivity of leucocytes to fast cooling rates, which were used in procedures that have been reported to yield viable pancreatic islets of Langerhans, was examined. The loss of both cell numbers and the ability of peripheral blood lymphocytes to undergo blastogenic transformation in response to the mitogen concanavalin A after freezing and thawing was determined over a range of cell concentrations using the “curve-shift” method. Lymphocytes frozen at 1 °C/min by a control procedure that was designed to yield maximum survival of lymphocytes showed that although there was a decrease in the number of responding cells, there was no reduction in the ability of the recovered cells to undergo blastogenesis when compared with the response of nonfrozen cells. However, cooling at 1 °C/min in the experimental procedures resulted in both the loss of cells as well as a marked reduction in the ability of recovered cells to incorporate 125I-deoxyuridine into nucleic acid. Cells cooled at either 20 or 75 °C/min by any of the procedures showed total inability to respond to stimulation. Lysozyme is produced continuously by all types of macrophages in culture. The large net increase in total lysozyme content of macrophage cultures is therefore a useful measure of the viability of these accessory cells. Cooling at 1 °C/min by a control, optimized procedure yielded 91% survival of viable peritoneal exudate cells. Cooling at either 1 or 20 °C/min in the experimental procedures resulted in 72–75% survival of cells frozen by one method and 33% survival when frozen by an alternative procedure. Negligible recovery of viable cells was obtained after cooling at 75 °C/min. The preservation protocols employed in this study differ significantly in the variables known to influence the survival of the cells; these include the concentration of cryoprotectant (CPA), the length and temperature of exposure to CPA, the dilution regimen, and the optimum cooling rate for survival of pancreatic islets. This study therefore defines clearly those conditions most likely to effect a depletion of “passenger” lymphoid cells by freezing during the Cryopreservation of islets of Langerhans.

The effects of different conditions of organ culture on the survival of the mouse pancreas.

The effects of different conditions of organ culture on the viability of murine pancreatic tissues and, particularly, of pancreatic islets, was assessed by morphologic and histochemical analyses. High oxygen tension (1300 mm Hg), found previously to allow successful allogeneic thyroid transplantation, was toxic to pancreatic tissue. Low temperature (22 degrees C) was associated with better islet preservation than high temperature (37 degrees C). Hydrocortisone did not reduce the survival of pancreatic islets and did appear to preserve the acinar components. Fetal and neonatal pancreas responded similarly to the various organ culture conditions. These results have potential importance in guiding future transplantation experiments.

Social Change in the South

Previous articleNext article No AccessThe Southern Political Scene, 1938-1948Social Change in the SouthHoward W. OdumHoward W. Odum Search for more articles by this author PDFPDF PLUS Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by The Journal of Politics Volume 10, Number 2May, 1948 Sponsored by the Southern Political Science Association Article DOIhttps://doi.org/10.2307/2125786 Views: 7Total views on this site Citations: 7Citations are reported from Crossref PDF download Crossref reports the following articles citing this article:Joon Ho Moon, Yeong Gi Kim, Kyuho Kim, Sho Osonoi, Shuang Wang, Diane C. Saunders, Juehu Wang, Katherine Yang, Hyeongseok Kim, Junguee Lee, Ji-Seon Jeong, Ronadip R. Banerjee, Seung K. Kim, Yingjie Wu, Hiroki Mizukami, Alvin C. Powers, Michael S. German, Hail Kim Serotonin Regulates Adult β-Cell Mass by Stimulating Perinatal β-Cell Proliferation, Diabetes 69, no.22 (Dec 2019): 205–214.https://doi.org/10.2337/db19-0546Steven White Civil Rights, World War II, and U.S. Public Opinion, Studies in American Political Development 30, no.11 (Apr 2016): 38–61.https://doi.org/10.1017/S0898588X16000055Xianyang Zhang, Tengjiao Cui, Jinlin He, Haibo Wang, Renzhi Cai, Petra Popovics, Irving Vidaurre, Wei Sha, Janine Schmid, Barbara Ludwig, Norman L. Block, Stefan R. Bornstein, Andrew V. Schally Beneficial effects of growth hormone-releasing hormone agonists on rat INS-1 cells and on streptozotocin-induced NOD/SCID mice, Proceedings of the National Academy of Sciences 112, no.4444 (Oct 2015): 13651–13656.https://doi.org/10.1073/pnas.1518540112Barbara Ludwig, Christian G. Ziegler, Andrew V. Schally, Claudius Richter, Anja Steffen, Normund Jabs, Richard H. Funk, Mathias D. Brendel, Norman L. Block, Monika Ehrhart-Bornstein, Stefan R. Bornstein Agonist of growth hormone-releasing hormone as a potential effector for survival and proliferation of pancreatic islets, Proceedings of the National Academy of Sciences 107, no.2828 (Jun 2010): 12623–12628.https://doi.org/10.1073/pnas.1005098107John Brueggemann Racial Considerations and Social Policy in the 1930s, Social Science History 26, no.11 (Jan 2016): 139–177.https://doi.org/10.1017/S0145553200012311Joseph M. Ray The Influence of the Tennessee Valley Authority on Government in the South, American Political Science Review 43, no.55 (Sep 2013): 922–932.https://doi.org/10.2307/1950233 Merritt B. Pound The Southern Political Science Association: An Inventory, The Journal of Politics 11, no.22 (Sep 2015): 285–297.https://doi.org/10.2307/2126278