BACKGROUND: Certain clinical conditions are associated with inappropriately high levels of circulating glucagon. To date, little information is available about the direct effects of prolonged exposure of human islet cells to pancreatic glucagon. In the present study we evaluated the function, antigenicity and survival of human islets exposed for 24 h to human pancreatic glucagon. METHODS: We prepared human islets of Langerhans by collagenase digestion and density-gradient purification, incubated them for 24 h with 44 or 430 pmol/l pancreatic glucagon at physiological (5.5 mmol/l) glucose level, and evaluated their insulin release function, which was then compared with that obtained from islets kept at high (11.1 mmol/l) glucose concentration. In addition, aliquots of the islets were evaluated to assess their chemotactic properties towards human monocyte-macrophage cells, and their potency to induce cytokine release from human lymphocytes. Finally, survival of the islet cells cultured under varying conditions was evaluated, and an assessment was performed of mRNA expression of Bcl-2 and Bax proteins. RESULTS: The insulin secretion results demonstrated that, compared to the control islets, the islets previously exposed to either 44 or 430 pmol/l glucagon exhibited changes in insulin release in response to glucose, consisting of augmented secretion at low glucose challenge, and no further significant increase at high glucose stimulation, similar to the effects observed with islets pre-cultured with high glucose. These effects were reversible, as documented by the recovery of normal islet sensitivity to glucose after an additional 24-h culture in medium lacking glucagon. Compared to control islets, the culture medium from islets pre-cultured with high glucagon or high glucose showed an increased chemotactic potency towards human monocyte-macrophage cells. In addition, human lymphocytes released a greater amount of tumour necrosis factor alpha when co-cultured with the islets pre-exposed to high glucagon or high glucose, whereas no significant difference was observed (in comparison with control islets) as regards the release of gamma-interferon, interleukin-2 and interleukin-10. The TUNEL technique and RT-PCR showed, respectively, no major difference in cell survival and expression of mRNA encoding for Bcl-2 and Bax protein between control islets and islets kept for 24 h in the presence of high glucagon or high glucose. CONCLUSIONS: Our results show that in vitro exposure of human islets to pancreatic glucagon for 24 h causes changes in the function and antigenicity of isolated human islets that are similar to the changes observed after pre-culture with increased glucose levels. Under our experimental conditions, these changes were not accompanied by any evidence of cytotoxicity.

Cell Survival↗

PubMedDate not supplied

[Retrospective demographic study in a small mountainous region of the province of Rome].

This retrospective study takes into consideration demographic and epidemiological data relative to the population of Arcinazzo Romano, a little village on the mountains situated at 831 m. above sea level in the province of Rome. The socio-economic structure of the village is mainly agropastoral, though, in the last decades, 50% of the ground has been left uncultivated due to emigration and commuting. ISTAT data relative to population censuses of 1951, 1961, 1971 and 1981 have been used to study the population natural movement from 1943 to 1987. The active/passive rate and the population ageing index have also been considered. Whenever possible local population data have been compared with similar data on a provincial, regional and national level. From 1943 (1697 inhabitants according to the archives of the Civil Status Office) the population of Arcinazzo R. has been increasing until 1955 (1903 inhabitants). Afterwards, there has been a slow, but constant, decrement till 1987 (1435 inhabitants). The reason for this is undoubtedly the migration movement (mainly towards Rome) due to the scarcity of job possibilities in the zone. This has resulted in a decrease in both active population and agricultural manpower. From 1943 to 1987 there has been a continuous decrease in birth-rate. Starting from 33.5 in 1943, the lowest value (4.6) is reached in 1981; in the last decade the index has settled on average values (11.22) which are slightly higher than national and regional averages (10.2 and 9.7 respectively). The general death-rate has its highest value in 1944 (19.3) and its lowest value in 1958 (4.8). From this date on, the index settles on an average of 12.0, which is slightly higher than national and regional averages (9.5 and 8.4 respectively). The infant death-rate starts from a value of 228/1000 in 1943 to decrease in following years. Keeping into account that the number of children born each year in Arcinazzo R. is very small, a comparison with national or regional averages is not felt to be appropriate. In fact, local values of this index may casually result very high: for instance, in 1981, the death of two premature twins, on a total of seven children born in the same year, brings the infant death-rate to a value of 285/1000 while in the years 1982-87 the infant death-rate is 0. The population natural growth index is obtained from the difference between general birth- and death-rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗