Arginine vasopressin-induced glucagon release: interaction with glucose and cyclic AMP-dependent protein kinase

The first study purpose was to investigate the glucose dependency of arginine vasopressin (AVP)-induced insulin, glucagon and somatostatin release from the perfused rat pancreas. AVP (30 or 300 pmol/L) was tested in the presence of glucose concentrations of 0, 1.4, 5.5 (basal level), or 20 mmol/L. The findings from this study suggested that AVP may increase insulin and glucagon release by a direct action on beta- and alpha-cells, respectively. These increases are glucose-dependent; the higher the glucose concentration, the greater the enhancement of AVP-induced insulin release. In contrast, the lower the glucose concentration, the greater the enhancement of AVP-induced glucagon release. AVP not only can enhance glucose-induced insulin release, but also can initiate insulin release. alpha-cells are much more sensitive to AVP than beta-cells in hormone release. Furthermore, our results confirmed the previous findings that hypoglycemia directly increases glucagon and decreases insulin release.;The second study purpose was to characterize the mechanisms by which cAMP/PKA enhances AVP-induced glucagon release and provide further details in the intracellular molecular components involved in this enhancement, particularly at the level of exocytosis. Increasing intracellular cAMP levels by forskolin or IBMX enhanced AVP-induced glucagon release from the perfused rat pancreas and the clonal alpha-cells InR1G9. cAMP/PKA did not increase [Ca 2+]i nor did it;enhance AVP-induced [Ca2+]i increase. Forskolin and IBMX enhanced AVP-induced glucagon release in Ca2+-containing but not in Ca2+-free medium. InR1G9 cells were loaded with styryl dye FM1-43 to measure the size of readily releasable pool (RRP). The combination of AVP and forskolin induced higher increase in fluorescence intensity than AVP or forskolin alone, which reflects an increase in the size of the RRP. Secretory granules in the reserve pool (RP) are thought to be reversibly connected to the actin-based cytoskeleton by synapsin I. Pretreatment with antisynapsin I antibody abolished the effect of forskolin/AVP-induced glucagon release. In addition, FM1-43 loading experiments showed that synapsin I is involved in recruitment of secretory granules from RP to RRP. Our results suggested that cAMP, acting through PKA, increases the number of secretory granules in the RRP by mobilization of granules from the RP, an action mediated by synapsin I

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security