Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet.

Elevated free fatty acids (FFAs) impair beta cell function and reduce beta cell mass as a consequence of the lipotoxicity that occurs in type 2 diabetes (T2D). We previously reported that the membrane protein caveolin-1 (CAV1) sensitizes to palmitate-induced apoptosis in the beta pancreatic cell line MIN6. Thus, our hypothesis was that CAV1 knock-out (CAV1 KO) mice subjected to a high fat diet (HFD) should suffer less damage to beta cells than wild type (WT) mice. Here, we evaluated the in vivo response of beta cells in the pancreatic islets of 8-week-old C57Bl/6J CAV1 KO mice subjected to a control diet (CD, 14% kcal fat) or a HFD (60% kcal fat) for 12 weeks. We observed that CAV1 KO mice were resistant to weight gain when on HFD, although they had high serum cholesterol and FFA levels, impaired glucose tolerance and were insulin resistant. Some of these alterations were also observed in mice on CD. Interestingly, KO mice fed with HFD showed an adaptive response of the pancreatic beta cells and exhibited a significant decrease in beta cell apoptosis in their islets compared to WT mice. These in vivo results suggest that although the CAV1 KO mice are metabolically unhealthy, they adapt better to a HFD than WT mice. To shed light on the possible signaling pathway(s) involved, MIN6 murine beta cells expressing (MIN6 CAV) or not expressing (MIN6 Mock) CAV1 were incubated with the saturated fatty acid palmitate in the presence of mitogen-activated protein kinase inhibitors. Western blot analysis revealed that CAV1 enhanced palmitate-induced JNK, p38 and ERK phosphorylation in MIN6 CAV1 cells. Moreover, all the MAPK inhibitors partially restored MIN6 viability, but the effect was most notable with the ERK inhibitor. In conclusion, our results suggest that CAV1 KO mice adapted better to a HFD despite their altered metabolic state and that this may at least in part be due to reduced beta cell damage. Moreover, they indicate that the ability of CAV1 to increase sensitivity to FFAs may be mediated by MAPK and particularly ERK activation.

Understanding toxicological implications of accidents with caterpillars Megalopyge lanata and Podalia orsilochus (Lepidoptera: Megalopygidae).

Megalopygids Megalopyge lanata and Podalia orsilochus are common causative agents of accidents in agricultural workers. These accidents are provoked by dermal contact at their larval stage and are characterized by cutaneous reactions, such as burning pain, edema and erythema, typically mild and self-limited. There is very little information about their venoms and their toxicological implications on human health. Thus, we employed proteomic techniques and biological assays to characterize venoms (bristle extracts) from caterpillars of both species collected from Misiones, Argentina. The electrophoretic profiles of both venoms were substantially different, and they presented proteins related to toxicity, such as serinepeptidases, serpins and lectins. P. orsilochus venom exhibited higher caseinolytic activity than M. lanata venom, agreeing with the fact that only P. orsilochus venom hydrolyzed human fibrin(ogen). In addition, the latter shortened the clotting time triggered by calcium. While the venom of M. lanata induced a mild inflammatory lesion in mouse skin, P. orsilochus venom caused prominent necrosis, inflammatory infiltration and hemorrhage at the site of venom injection. On the other hand, P. orsilochus venom was better recognized by Lonomia obliqua antivenom, although many of its proteins could not be cross-reacted, what may explain the difference in the clinical manifestations between accidents by Podalia and those by Lonomia. Altogether, this study provides relevant information about the pathophysiological mechanisms whereby both caterpillars can induce toxicity on human beings, and paves the way for novel discovery of naturally occurring bioactive compounds.