Using Tracking Data to Promote Environmental Public Health Through Regulatory and Legislative Processes in New York City.

Legislation and regulation are powerful tools for decreasing health risks from environmental hazards. Legislation is enacted by an elected body, and regulations are issued by an agency in the executive branch delegated authority by the legislature to carry out enacted laws. The New York City (NYC) Environmental Public Health Tracking Program makes data and analytic findings available to policy makers to inform development of sound and effective environmental health legislation and regulation. Tracking data and associated science create awareness of environmental hazards and health impacts, guide strategies for mitigating hazards, and sustain support for effective law by documenting beneficial impacts on the environment and health. We describe how environmental and health surveillance data and analytic findings have informed legislation and regulations related to restaurant food safety and air pollution control in NYC. Using data to guide legislative and regulatory processes helps ensure that policy decisions and directions are based on objective evidence.

Insulin receptor phosphorylation by endogenous insulin or the insulin analog AspB10 promotes mammary tumor growth independent of the IGF-I receptor.

Endogenous hyperinsulinemia and insulin receptor (IR)/IGF-I receptor (IGF-IR) phosphorylation in tumors are associated with a worse prognosis in women with breast cancer. In vitro, insulin stimulation of the IR increases proliferation of breast cancer cells. However, in vivo studies demonstrating that IR activation increases tumor growth, independently of IGF-IR activation, are lacking. We hypothesized that endogenous hyperinsulinemia increases mammary tumor growth by directly activating the IR rather than the IGF-IR or hybrid receptors. We aimed to determine whether stimulating the IR with the insulin analog AspB10 could increase tumor growth independently of IGF-IR signaling. We induced orthotopic mammary tumors in control FVB/n and hyperinsulinemic MKR mice, and treated them with the insulin analog AspB10, recombinant human IGF-I, or vehicle. Tumors from mice with endogenous hyperinsulinemia were larger and had greater IR phosphorylation, but not IGF-IR phosphorylation, than those from control mice. Chronic AspB10 administration also increased tumor growth and IR (but not IGF-IR) phosphorylation in tumors. IGF-I led to activation of both the IGF-IR and IR and probably hybrid receptors. Our results demonstrate that IR phosphorylation increases tumor growth, independently of IGF-IR/hybrid receptor phosphorylation, and warrant consideration when developing therapeutics targeting the IGF-IR, but not the IR.

Deletion of growth hormone receptors in postnatal skeletal muscle of male mice does not alter muscle mass and response to pathological injury.

In this study, we investigated whether loss of GH receptor (GHR) signaling in postnatal skeletal muscle alters muscle mass and regenerative ability in adult mice and whether this was dependent on IGF-1 receptor (IGF-1R) signaling. To do so, we used mouse models with skeletal muscle-specific loss of GHR signaling (mGHRKO), IGF-1R and insulin receptor signaling (MKR), or both GHR and IGF-1R/insulin receptor signaling (mGHRKO/MKR). We did not find a reduction in muscle cross-sectional area, fiber type composition, or response to pathological muscle injury in male mGHRKO and mGHRKO/MKR mice when compared with control and MKR mice, respectively. This could potentially be explained by unchanged skeletal muscle Igf-1 expression in mGHRKO and mGHRKO/MKR mice relative to control and MKR mice, respectively. Furthermore, MKR and mGHRKO/MKR mice, but not mGHRKO mice, demonstrated reduced fiber fusion after cardiotoxin injection, suggesting that IGF-1, and not GH, promotes fiber fusion in adult mice. In summary, our data suggest that GHR signaling in postnatal skeletal muscle does not play a significant role in regulating muscle mass or muscle regeneration. Additionally, in our model, muscle Igf-1 expression is not dependent on GHR signaling in postnatal skeletal muscle.