Type I diabetes mellitus is strongly genetically linked to the major histocompatibility complex but relatively few potentially susceptible people, who are presumably frequently exposed to appropriate triggering factors (e.g. viral illness, environmental agents), develop overt disease. It is possible that some such individuals show latent disease (e.g. islet cell antibodies and perhaps local pancreatic pathology) that does not progress. On the basis of animal data and some clinical evidence we speculate that latent disease is controlled by suppressor cells. We suggest that physiological immunosuppression (e.g. with glucocorticoids) may selectively inactivate such T suppressor cells. Such immunomodulation may allow further islet cell destruction to occur and repeated episodes could eventually produce diabetes. Such episodes of altered immunoregulation may be due to intercurrent viral illness, stress, or therapy with low doses of immunosuppressive agents.

Animals↗

PubMed1986

A comparison of portal versus systemic venous drainage in murine foetal pancreatic islet transplantation.

We have compared the efficiency of foetal islet graft growth and function in renal subcapsular (systemic drainage) and splenic (portal drainage) sites. Age-matched female BALB/c streptozotocin (STZ)-diabetic mice were grafted either under the left renal capsule or on to the hilar surface of the spleen with one half of a syngeneic 17-day gestation foetal pancreas which had been in organ culture for 2 weeks. Gain in body weight, return to normoglycaemia and to normal glycosylated haemoglobin levels were not significantly different between the two groups. However, when an intraperitoneal arginine challenge was performed the portally grafted mice showed more normal responses than the systemically grafted mice. Although still not normal after the arginine challenge, mean blood glucose values were lower and serum insulin values higher in the spleen grafted animals than in the renal subcapsular graft group. The total amount of insulin was assayed by extraction of both the graft and the pancreas of each animal. The amount of insulin in the grafts from the spleen was not significantly different from those in the renal subcapsular site. We conclude that the efficiency of a graft draining into the portal circulation is greater than an equivalent sized graft draining systemically when a maximal challenge is applied.

Animals↗

PubMed1986

Fetal pancreatic islet transplantation in H-2 disparate congenic mice.

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Animals↗

PubMed1986

Anatomy of the mouse retina. Capillary basement membrane thickness.

Transmission electron microscopy of ultrathin sections was used to measure mouse retinal capillary basement membrane thickness (BMT). BMT increases predictably with age from 50 +/- 9 nm at 6 weeks to 154 +/- 27 nm at 20 months, but is not affected by strain or sex. There is an effect of retinal site, however, with BMT increasing with the radial distance from the optic nerve, 41 +/- 4 nm (center), 54 +/- 5 nm (mid-zone), and 64 +/- 6 nm (periphery). The layer of retina from which capillaries were taken had no effect on BMT, and the inner and outer BMT maintained a consistent ratio, even at different ages.

Animals↗

PubMed1986

Anatomy of the mouse retina. Endothelial cell-pericyte ratio and capillary distribution.

A technique is described for preparing whole retinal vascular digests using distilled water and DNase. This produces a more satisfactory preparation of the mouse retinal vascular bed than "trypsin digestion." Nonetheless, the calculation of endothelial cell/pericyte (E/P) ratios based on cell counts from digest preparations has poor reproducibility due to the inability to unequivocally identify at least 25% of the cells in conventionally stained (PAS and hematoxylin) preparations. A more accurate and reproducible means of assessing this ratio uses 1 micron sections of plastic-embedded sections of retina. No effect of age, sex, strain, or area of sampling was found. Capillaries were in three specific bands, centered on the nerve fiber layer, the junction of inner plexiform and inner nuclear layers, and the outer plexiform layers.

Animals↗

PubMed1985

The use of immature pancreas as a source of tissue for transplantation in diabetes.

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Aborted Fetus↗

PubMed1985

Effect of culture conditions on fetal mouse pancreas in vitro and after transplantation in syngeneic and allogeneic recipients.

Organ culture of fetal mouse pancreas under conditions designed to either maximally preserve islet cell survival or reduce immunogenicity was used to test the efficacy of islet graft function in diabetic syngeneic or fully allogeneic recipients. Organ culture in either 90% O2, or at low temperature (22 degrees C), or in a combination of 90% O2 and 22 degrees C for 14 days not only failed to reduce immunogenicity in fully allogeneic recipients but also diminished endocrine cell survival in grafts in syngeneic recipients. Monitoring of in vitro insulin secretion provided a better guide to future graft function than did the insulin content of the cultured tissue. It is concluded that culture conditions that have been shown to reduce immunogenicity (high O2 concentration and low temperature) are not synergistic when used together and are also potentially damaging to endocrine cells.

Animals↗