Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism.

Progesterone has been associated with the development of gestational diabetes (GD) due to the enhancement of insulin resistance. As ß-cell apoptosis participates in type 1 and type 2 diabetes pathophysiology, we proposed the hypothesis that progesterone might contribute to the development of GD through a mechanism that also involves ß-cell death. To address this question, RINm5F insulin-producing cells were incubated with progesterone (25-100 µM), in the presence or absence of α-tocopherol (40 µM). After 24 or 48 h, membrane integrity and DNA fragmentation were analyzed by flow cytometry. Caspase activity was used to identify the mode of cell death. The involvement of endoplasmic reticulum stress in the action of progesterone was investigated by western blotting. Oxidative stress was measured by 2',7'-dichlorofluorescein diacetate (DCFDA) oxidation. Isolated rat islets were used in similar experiments in order to confirm the effect of progesterone in primary ß-cells. Incubation of RINm5F cells with progesterone increased the number of cells with loss of membrane integrity and DNA fragmentation. Progesterone induced generation of reactive species. Pre-incubation with α-tocopherol attenuated progesterone-induced apoptosis. Western blot analyses revealed increased expression of CREB2 and CHOP in progesterone-treated cells. Progesterone caused apoptotic death of rat islet cells and enhanced generation of reactive species. Our results show that progesterone can be toxic to pancreatic ß-cells through an oxidative-stress-dependent mechanism that induces apoptosis. This effect may contribute to the development of GD during pregnancy, particularly under conditions that require administration of pharmacological doses of this hormone.

Estudo anatômico do plexo lombossacral de Tamandua tetradactyla / Anatomical study of the lumbosacral plexus of the Tamandua tetradactyla

O tamanduá-mirim (Tamandua tetradactyla) é um xenartro da família Myrmecophagidae, encontrado da Venezuela ao sul do Brasil. Estudos apontam que essa é uma das espécies de animais selvagens mais vitimadas em número de atropelamentos, e, muitas vezes, o atendimento clínico adequado aos indivíduos feridos é dificultado pela carência de informações acerca dos mesmos. Visando contribuir com o conhecimento dessa espécie, este estudo teve como objetivo descrever seu plexo lombossacral. Para tanto, foram utilizados quatro cadáveres de Tamandua tetradactyla adultos e de ambos os sexos. O plexo lombossacral dessa espécie é formado pelos ramos ventrais dos nervos espinhais T18, L1, L2, L3, S1, S2, S3, S4, S5. Os nervos integrantes do plexo lombossacral do T. tetradactyla com suas formações mais frequentes foram os seguintes: genitofemoral (T18), cutâneo femoral lateral (T18-L1), femoral (T18, L1-L3), obturador (T18, L1-L3), glúteo cranial (L3-S1), isquiático (L3-S3), pudendo (S3-S4 ou S4-S5), retal caudal (S4 ou S5) e cutâneo femoral caudal (S4-S5). O plexo lombar e sacral dessa espécie é unido, sendo L3 o ponto de união entre eles. Devido ao pequeno número de vértebras lombares, a composição dos nervos do plexo lombossacral do T. tetradactyla apresenta características peculiares que se diferem das características das demais espécies já estudadas, quais sejam, a ausência dos nervos ílio-hipogástrico e ilioinguinal e participação de nervos torácicos na composição dos nervos do plexo lombar, presença de contribuição sacral na composição do nervo obturador e ausência de contribuição lombar na composição do nervo isquiático e um limite mais caudal na extensão do plexo sacral.

The lesser anteater (Tamandua tetradactyla) is a xenarthra of the Myrmecophagidae family found from Venezuela to southern Brazil. Studies have shown that this is one of the most numerous wildlife species victims of car collisions on roads, and often the appropriate clinical care to injured animals is hindered by the lack of information about them. In order to contribute to the knowledge of this species, this study aimed to describe its lumbosacral plexus. For this purpose, four cadavers of adult specimens of both sexes of T. tetradactyla were used. The lumbosacral plexus of the T. tetradactyla is formed by the ventral rami of spinal nerves T18, L1, L2, L3, S1, S2, S3, S4, S5. The lumbosacral plexus nerves with their most common formations in this species were as follows: genitofemoral (T18), lateral femoral cutaneous (T18-L1), femoral (T18, L1-L3), obturator (T18, L1-L3), cranial gluteal (L3-S1), ischiatic (L3-S3), pudendus (S3-S4 or S4-S5), caudal retal (S4 or S5), and caudal femoral cutaneous (S4-S5). The lumbar and sacral plexus of this species is joined, L3 being the link between them. Due to the small number of lumbar vertebrae, the arrangement of the lumbosacral plexus nerves of the T. tetradactyla showed peculiar characteristics that differ it from that of other previously studied species, such as the absence of iliohypogastric and ilioinguinal nerves and contribution of thoracic nerves in the formation of all the nerves of the lumbar plexus, presence of sacral contribution in the formation of the obturator nerve, and the lack of lumbar contribution for sciatic nerve formation and a most caudal extent of the sacral plexus.