Cell-to-cell interactions play an important role in the development and maintenance of the beta-cell phenotype. Here, we have investigated whether E-cadherin plays a role in regulating the growth of insulin-secreting MIN6 cells configured as three-dimensional islet-like clusters (pseudoislets). Pseudoislets form by cell aggregation rather than by proliferation from individual cells and attain the size of primary mouse islets after approximately 7 days of maintenance in culture. E-cadherin is known to mediate homotypic cell adhesion between beta-cells and has also been implicated in a number of cellular processes, including proliferation, apoptosis, and differentiation. E-cadherin and its associated intracellular elements, alpha- and beta-catenin, were upregulated in MIN6 pseudoislets. Pseudoislet formation was associated with an increased expression of cyclin-dependent kinase inhibitors and a concomitant downregulation of Ki67, suggesting an overall reduction in cellular proliferation. However, measurements of 5-bromo-2'-deoxyuridine incorporation revealed that there were no differences in the rate of MIN6 cell proliferation whether they were configured as monolayers or as pseudoislets, which is likely to be a result of their being a transformed cell line. Cells within pseudoislets were not necrotic, but apoptosis appeared to be upregulated in the islet-like structures. However, no differential expression of Fas and FasL was detected in monolayers and pseudoislets. These results suggest that cell-to-cell interactions within islet-like structures may initiate antiproliferative and proapoptotic signals.

Using continuous glucose monitoring we were able to demonstrate that a period of moderate exercise improved whole-day glycemic control in obese individuals with type 2 diabetes. The CGMS should only be used as an adjunct and not as an alternative to frequent blood glucose sampling when examining the changes in glucose values during exercise in individuals with and without type 2 diabetes.

Treatment of neonatal rat islets of Langerhans with combined cytokines (interleukin-1L L 10 3IH M, tumour necrosis factor-K K 10 3IH M, interferon-Q Q 5 U/ml) led to extensive cell death, which was potentiated by Fas activation with the anti-Fas cytolytic antibody JO2. Pre-treatment with insulin (25 ng/ml) or insulin-like growth factor-1 (10 3V M) gave only partial protection against cell killing, but prevented the Fas-mediated component. In the absence of cytokine treatment, Fas-mediated killing was not observed.z 1998 Federation of European Biochemical Societies.

In stent restenosis (ISR) has been described as an unaccomplished tissue healing and its rate is particularly high in diabetic patients. Evidence has been collected which relates the formation of ISR proteoglycan-rich neointimal tissue to the accumulation and protracted activation of macrophages around the stent metal struts. Here, the in vitro activation of mononuclear cells adhering to stainless steel (a material of choice in stent manufacturing) from control and diabetic (types 1 and 2) subjects was assessed in the presence of different glucose levels. The results showed that cells from the control and type 1 diabetes groups produced significantly higher levels of TGF-beta1 when adhering on stainless steel (p = 0.04 and p = 0.01), but a significant PDGF-BB secretion was observed only in control subjects. When tested at physiological glucose concentration, the effect of the stainless steel on control cells was more pronounced. The present study shows that mononuclear cells adhering onto stainless steel secrete growth factors relevant to ISR. Cells from diabetic subjects seem to secrete relatively higher levels of PDGF under hyperglycaemic conditions regardless of the substrate exposed thus offering an explanation for the higher incidence of restenosis in these patients.

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