The non-obese diabetic (NOD) mouse was used to investigate the effects of voluntary wheel running exercise on blood glucose levels, glycosylated hemoglobin, and longevity in Type 1 diabetes mellitus. In Experiment 1, diabetic and normoglycemic mice exercised 5 h/day, 5 days/week for 3 weeks matched with non-exercising controls. In diabetic animals a positive correlation was found between blood glucose and the number of revolutions performed (P < or = 0.02). Exercise also significantly lowered blood glucose between baseline and post-exercise in both diabetic and normoglycemic animals. In Experiment 2, mice exercised 2 h/day, 5 days/week. For the diabetic animals, glycosylated hemoglobin was lower than that of matched non-exercising diabetic animals at week 3 (11.1 +/- 0.6% vs. 15.0 +/- 1.6%, P < 0.001). Diabetic runners were able to train and significantly increased running in the first 4 weeks (P < 0.05). At the end of 9 weeks all 5 diabetic runners were alive, compared with 3 of 5 non-running diabetic animals. We conclude: (i) the NOD mouse is a useful model for the study of exercise in Type 1 diabetes, (ii) running exercise is associated with a drop in blood glucose, (iii) the amount of voluntary exercise performed correlates with blood glucose in diabetic animals, and (iv) diabetic mice will increase running distance in the first few weeks after diagnosis.

Animals↗

PubMedDate not supplied

Human fetal pancreas transplants.

Human fetal pancreatic islet tissue has several advantages as a transplant source for the amelioration of insulin deficiency in patients with Type I diabetes mellitus. It is now possible to obtain viable tissue, store and ship the tissue without adverse effects on the insulin secretory capacity, and transplant either minced tissue or isolated islet-like cell clusters following digestion and culture into animal models or man. A number of centers have undertaken studies of human fetal pancreatic allografts in man. Optimal results have occurred when pooled tissue from six to 20 donors has been implanted and a number of sites have been studied. The author's own experience in four recipients who did not receive immunosuppression has documented insulin secretion for up to 1 year in the absence of an anticytoplasmic islet cell antibody response on the part of the recipients. Nevertheless, the procedure has not resulted in insulin independence for the recipients and the implanted tissue has not secreted insulin in response to a glucose-amino acid challenge in a normal physiologic pattern. Thus, human fetal pancreatic transplantation for the treatment of Type I diabetes remains an experimental approach.

Animals↗

PubMedDate not supplied

Effect of glipizide on insulin secretion from cultured human fetal pancreatic islets.

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1-Methyl-3-isobutylxanthine↗

PubMedDate not supplied

Progesterone induces apoptosis in malignant mesothelioma cells.

Progesterone has been used in the treatment of patients with recurrent or metastatic progesterone receptor-positive endometrial carcinoma and breast cancer. In vitro study using a breast cancer cell line, T47D, demonstrated an increase in p53 gene expression and induction of apoptosis by the administration of progesterone. Therefore, we investigated the effect of progesterone administration on the proliferation and apoptosis in a mesothelioma cell line, 211H. The expression of the progesterone receptor gene was detected in this cell line by a nested RT-PCR method. The proliferation of the cell line was suppressed after a 10-day incubation with 30 microM progesterone. In progesterone-treated 211H cells, apoptotic cells were detected by TUNEL assay and nuclear DNA fragmentation analysis. These results clearly demonstrated that progesterone administration suppressed the cell proliferation and induced apoptosis in malignant mesothelioma cells.

Apoptosis↗

PubMedDate not supplied

T cell vaccination against autoimmune diabetes in nonobese diabetic mice.

The diabetogenic autoimmune process was accelerated in 23 days nonirradiated postnatal nonobese diabetic (NOD) female mice by adoptive transfer of pathogenic, polyclonal CD4+ 8- T cells isolated from diabetic spleens. Recipient mice developed hyperglycemia 15 days after transfer of pathogenic immune cells with typical histological signs of pancreatic infiltration. The CD4+V beta 8+ T cells isolated from diabetic spleens and activated by surface-immobilized anti-TCRV beta 8 monoclonal antibody (mAb, clone F23.1) induced suppression of a diabetogenic disease process accelerated earlier by adoptively transferred polyclonal CD4+8- T cells. When CD4+V beta 8+ T cells isolated from diabetic spleens were activated by cross-linking TCRV beta 8 and systemically injected into young female NOD mice, an endogenous immunosuppressive circuit was stimulated that completely prevented development of insulitis and disease. A suppressor mechanism involving CD8+ T cells might be involved since in vitro these cells strongly proliferated in response to irradiated CD4+ V beta 8+ T cells that in blocking experiments with specific mAb was found to be class I major histocompatibility complex (MHC)-restricted. Hence, T cells expressing the CD8 phenotype specifically respond to idiotypic or ergotypic determinants on the inducing activated CD4+V beta 8+ T cells and effectively suppress a diabetogenic disease process by a mechanism that may involve T-T cell interactions.

Animals↗

PubMedDate not supplied

Progesterone inhibits growth and induces apoptosis in breast cancer cells: inverse effects on Bcl-2 and p53.

Progesterone inhibits the proliferation of normal breast epithelial cells in vivo, as well as breast cancer cells in vitro. But the biologic mechanism of this inhibition remains to be determined. We explored the possibility that an antiproliferative activity of progesterone in breast cancer cell lines is due to its ability to induce apoptosis. Since p53 and bcl-2 genetically control the apoptotic process, we investigated whether or not these genes could be involved in the progesterone-induced apoptosis. We found a maximal 90 percent inhibition of cell proliferation with T47-D breast cancer cells after exposure to 10 microM progesterone for 72 hours. Control progesterone receptor negative MDA-231 cancer cells were unresponsive to these two concentrations of progesterone. After 24 hours of exposure to 10 microM progesterone, cytofluorometric analysis of T47-D breast cancer cells demonstrated 43 percent had undergone apoptosis without signs of necrosis. After 72 hours of exposure to 10 microM progesterone, 48 percent of the cells had undergone apoptosis and 40 percent demonstrated "leaky" membranes. Untreated cancer cells did not undergo apoptosis. Evidence proving apoptosis was also demonstrated by fragmentation of nuclear DNA into multiples of oligonucleosomal fragments. After 24 hours of exposure to either 1 microM or 10 microM progesterone, the expression by T47-D cancer cells of bcl-2 was down-regulated, and that of p53 was up-regulated as detected by semiquantitative RT-PCR analysis. These results demonstrate that progesterone at a concentration similar to that seen during the third trimester of pregnancy exhibited a strong antiproliferative effect on at least two breast cancer cell lines. Apoptosis was induced in the progesterone receptor expressing T47-D breast cancer cells.

Apoptosis↗