KCNH6 channel promotes insulin exocytosis via interaction with Munc18-1 independent of electrophysiological processes.

Glucose-stimulated insulin secretion (GSIS) in pancreatic islet ß-cells primarily relies on electrophysiological processes. Previous research highlighted the regulatory role of KCNH6, a member of the Kv channel family, in governing GSIS through its influence on ß-cell electrophysiology. In this study, we unveil a novel facet of KCNH6's function concerning insulin granule exocytosis, independent of its conventional electrical role. Young mice with ß-cell-specific KCNH6 knockout (ßKO) exhibited impaired glucose tolerance and reduced insulin secretion, a phenomenon not explained by electrophysiological processes alone. Consistently, islets from KCNH6-ßKO mice exhibited reduced insulin secretion, conversely, the overexpression of KCNH6 in murine pancreatic islets significantly enhanced insulin release. Moreover, insulin granules lacking KCNH6 demonstrated compromised docking capabilities and a reduced fusion response upon glucose stimulation. Crucially, our investigation unveiled a significant interaction between KCNH6 and the SNARE protein regulator, Munc18-1, a key mediator of insulin granule exocytosis. These findings underscore the critical role of KCNH6 in the regulation of insulin secretion through its interaction with Munc18-1, providing a promising and novel avenue for enhancing our understanding of the Kv channel in diabetes mechanisms.

The signaling protein GIV/Girdin mediates the Nephrin-dependent insulin secretion of pancreatic islet ß cells in response to high glucose.

Glucose-stimulated insulin secretion of pancreatic ß cells is essential in maintaining glucose homeostasis. Recent evidence suggests that the Nephrin-mediated intercellular junction between ß cells is implicated in the regulation of insulin secretion. However, the underlying mechanisms are only partially characterized. Herein we report that GIV is a signaling mediator coordinating glucose-stimulated Nephrin phosphorylation and endocytosis with insulin secretion. We demonstrate that GIV is expressed in mouse islets and cultured ß cells. The loss of function study suggests that GIV is essential for the second phase of glucose-stimulated insulin secretion. Next, we demonstrate that GIV mediates the high glucose-stimulated tyrosine phosphorylation of GIV and Nephrin by recruiting Src kinase, which leads to the endocytosis of Nephrin. Subsequently, the glucose-induced GIV/Nephrin/Src signaling events trigger downstream Akt phosphorylation, which activates Rac1-mediated cytoskeleton reorganization, allowing insulin secretory granules to access the plasma membrane for the second-phase secretion. Finally, we found that GIV is downregulated in the islets isolated from diabetic mice, and rescue of GIV ameliorates the ß-cell dysfunction to restore the glucose-stimulated insulin secretion. We conclude that the GIV/Nephrin/Akt signaling axis is vital to regulate glucose-stimulated insulin secretion. This mechanism might be further targeted for therapeutic intervention of diabetic mellitus.

Geospatial Prioritization to Reach Hispanic or Latino and Other Priority Populations Through HIV Home Testing Services.

CONTEXT: Hispanic or Latino men who have sex with men (HLMSM) are disproportionately affected by the HIV/AIDS epidemic in New York State (NYS) and nationally. In 2019, HLMSM comprised 13% of all new diagnoses and 21% of new diagnoses among men who have sex with men (MSM) in NYS excluding New York City. HIV home testing programs are effective methods for increasing HIV testing. OBJECTIVE: This pilot sought to determine whether the NYS HIV Home Test Giveaway (HHTG) can effectively reach priority populations, specifically HLMSM/transgender/gender nonconforming persons who have sex with men, to increase uptake of HIV home testing services and identify new HIV infections. DESIGN/SETTING: We recruited participants using media campaigns linked to a brief self-administered eligibility survey. Eligible participants provided their e-mail address to receive a code for a free HIV home test and were sent a self-administered follow-up survey 4 to 11 weeks after eligibility survey completion. PARTICIPANTS: The 2018 and 2019 NYS HHTG reached 1214 and 1340 participants, respectively. A total of 606 participants in 2018 and 736 participants in 2019 were eligible to receive the HHTG home test kit. MAIN OUTCOME MEASURES: HHTG utilization and test results. RESULTS: Hispanic or Latino persons participated at higher rates (34.8% and 25.4% in 2018 and 2019, respectively) than the percentage of Hispanic men in prioritized zip codes (15.7% and 15.6% in 2018 and 2019, respectively). The majority of participants who received HHTG test kits used them to test themselves (87.5% in 2018 and 90.6% in 2019). Across both rounds, 4 participants reported new HIV-positive results, for a seropositivity rate of approximately 1%. CONCLUSION: Geospatial prioritization was successful in reaching Hispanic or Latino priority populations for HIV testing. HIV self-testing programs such as the HHTG are beneficial methods to reach priority populations for state and national Ending the HIV Epidemic initiatives.

Combating Stigma Through HIV Self-Testing: New York State's HIV Home Test Giveaway Program for Sexual Minorities.

CONTEXT: Gay, bisexual, and men who have sex with men (MSM) are disproportionately affected by the HIV/AIDS epidemic more than any other group. In New York State (NYS) outside of New York City (NYC), MSM accounted for 57% of new HIV/AIDS diagnoses in 2017. HIV/AIDS home testing initiatives have been effective at getting priority populations tested for HIV. OBJECTIVES: The NYS Department of Health (NYSDOH) administered the HIV Home Test Giveaway (HHTG) program through social media and mobile applications popular among the priority populations to (1) promote HIV screening among gay and bisexual men, MSM, transgender (TG), and gender queer/gender nonconforming (GNC) individuals who have sex with men, and (2) identify individuals with undiagnosed HIV infection. DESIGN/SETTING: The NYSDOH recruited participants from NYS (excluding NYC) through social media campaigns between November 2016 and January 2018. Interested individuals were directed to an online eligibility survey. Eligible participants received a coupon via e-mail for a free HIV self-test (HIVST) kit through the manufacturer's Web site. Eligible participants received a $20 to $25 Amazon online gift card if they completed a voluntary online follow-up survey regarding their test results, experiences with the HHTG, and HIV/AIDS risk behaviors. Participants were also able to request assistance from the NYSDOH with further testing and various prevention and supportive services. PARTICIPANTS: In total, 6190 individuals participated and 3197 (52%) were eligible and received a coupon. Of the eligible, 2022 (63%) redeemed coupons for HIVST. RESULTS: Among eligible participants, 976 (31%) reported having never been tested for HIV. On the follow-up survey, 922 (29%) participants reported having used the HIVST kit for themselves; 203 (22%) were first-time testers; and 7 (0.8%) tested HIV reactive. Of the follow-up survey participants, 761 (59%) requested assistance with various services. CONCLUSIONS: Media campaigns were effective in promoting HIV testing among priority populations and reaching individuals who have never been tested for HIV.

Assessing the Impact of a PrEP Aware Week Campaign on PrEP Prescription Fills in NYS.

CONTEXT: The New York State (NYS) Department of Health AIDS Institute engaged stakeholders across NYS to participate in the state's first "PrEP Aware Week" (PAW). PAW sought to increase the knowledge, interest, and number of PrEP (pre-exposure prophylaxis) prescriptions filled across NYS. PAW activities were designed to be easy to implement, with minimal cost. Stakeholders were provided activities to implement, along with a social media tool kit featuring videos, graphic ads, and sample social media posts in English and Spanish to use as is or modify. PAW included more than 750 distinct events and activities undertaken by more than 250 participating providers. OBJECTIVE: To assess the impact of PAW on PrEP prescription filling patterns in NYS. DESIGN: An interrupted time-series analysis was conducted to estimate the impact of PAW on overall and new PrEP prescription filling patterns. Separate models were developed by sex (male, female), race and ethnicity (White non-Hispanic, Black non-Hispanic, Hispanic, other, unknown), and region (New York City, rest of NYS). SETTING: PAW took place across NYS during the week beginning October 20, 2019. PARTICIPANTS: PAW was undertaken by more than 250 health care providers, nonmedical health & human services providers, local and state health department staff, and colleges and universities. MAIN OUTCOME MEASURES: The number of overall and new PrEP prescriptions. RESULTS: PAW was associated with modest increases (6%-9%) in the number of PrEP prescription fills in NYS. The PAW impact lasted for about 2 months, generated an estimated 2727 additional PrEP prescription fills statewide, and was realized across sex, region, and racial and ethnic subgroups. Increased prescription fills were driven by those previously prescribed PrEP. Increases in new prescriptions were noted among Latinx individuals (21% increase, 55 additional prescriptions) but not overall or across other groups. CONCLUSION: NYS's PAW was effective at increasing PrEP prescription refills in NYS.

A Peek Into the Future: How a Pandemic Resulted in the Creation of Models to Predict the Impact on Sexually Transmitted Infection(s) in New York State (Excluding New York City).

ABSTRACT: During the initial height of COVID-19 in New York State excluding New York City in March 2020, reports of sexually transmitted infections declined. Prediction models developed to estimate the incidence of early syphilis and gonorrhea during the COVID-19 pandemic were used to study impact on STI diagnoses/reporting and inform sexual health program planning.

The impact of implementation of oral dextrose gel on the incidence of multiple hypoglycemia events in the well newborn nursery.

OBJECTIVE: Evaluate the impact of 40% oral dextrose gel (DG) for management of neonatal hypoglycemia (NH) on the incidence of multiple hypoglycemic events in the well-baby nursery. STUDY DESIGN: A retrospective chart review of 738 at-risk infants in 2 cohorts before (Cohort 1) and after (Cohort 2) DG implementation. Primary outcome was the incidence of ≥2 hypoglycemic episodes. Secondary outcomes were number of lowest median glucose level, and incidence of NICU admission. RESULTS: There were 384 and 354 at-risk newborns in Cohorts 1 & 2. The incidence of developing ≥2 hypoglycemia episodes significantly decreased following DG implementation [62(42.5%) vs 29(25.9%), p = 0.0058]. There were no differences in lowest glucose level [37 (14-45) vs 37 (10-45), p = 0.31], and NICU admission rate [31 (21.2%) vs 21 (18.8%), p = 0.62]. CONCLUSIONS: Implementation of DG lowers the incidence of subsequent hypoglycemia episodes.

Impact of COVID-19 on HIV Testing Among AIDS Institute-Funded Providers in New York State-A Time Series Analysis.

BACKGROUND: New York State (NYS) was at the intersection of the HIV epidemic and coronavirus disease 2019 (COVID-19) pandemic leading to a disruption in HIV-preventive services. This study sought to determine the impact of the COVID-19 pandemic and mitigation efforts on HIV-testing trends in NYS among AIDS Institute (AI)-funded providers. METHODS: We analyzed weekly testing data from the AI Reporting System from January 1, 2017, to June 27, 2021, to fit an interrupted time series model that predicted the expected number of HIV tests among AI-funded providers in NYS had the COVID-19 pandemic not occurred. The actual observed numbers of HIV testing that occurred from weeks beginning March 15, 2020, to June 30, 2021, were compared with the number of HIV tests predicted by the model. RESULTS: In the absence of the COVID-19 pandemic, our model predicted that there would have been 45,605 HIV tests among AI-funded providers between the weeks beginning March 15, 2020, to June 27, 2021. We observed 20,742 HIV tests, representing a 54.5% reduction. We observed percent decreases of greater than 50% for HIV testing among AI-funded providers for New York City (52.9%) and rest of state (59.8%) regions, male (50.6%) and female (66.8%) genders, as well as Black (59.2%), Hispanic (52.8%), mixed race (57.5%), other (50.3%), and White (50.1%) race and ethnicities. CONCLUSION: HIV testing among AI-funded providers in NYS has declined substantially following the COVID-19 pandemic, reflecting decreased access to, and/or demand for, testing among persons at elevated risk for HIV. Initiatives to increase HIV testing and maintain access to HIV prevention services need to be explored following COVID-19.

Incidence of Type 1 Diabetes May Be Underestimated in the Chinese Population: Evidence From 21.7 Million People Between 2007 and 2017.

OBJECTIVE: Previous reports of the annual incidence of type 1 diabetes (T1D) in China were conducted using retrospective hospital cases, which may not reflect the reality. This longitudinal study estimated T1D incidence in a Chinese population of 21.7 million from 2007 to 2017. RESEARCH DESIGN AND METHODS: A population-based registry of T1D was performed by the Beijing Municipal Health Commission Information Center. Annual incidence and 95% CIs were calculated by age group and sex. The association of sex with T1D incidence and predicted new cases of T1D were assessed using Poisson regression models. Annual percentage change and average annual percentage of change were assessed using Joinpoint regression. RESULTS: Overall, there were 6,875 individuals who developed T1D from 2007 to 2017 in this population. T1D incidence (/100,000 persons) (95% CI) significantly increased from 2.72 (2.51, 2.93) in 2007 to 3.60 (3.38, 3.78) in 2017 (P < 0.001). The T1D onset peak was in the 10-14-year-old age group. While no significant trend was found in the 0-14- and 15-29-year-old age groups, T1D incidence markedly increased from 1.87 to 3.52 in the ≥30-year-old age group (P < 0.05). The prevalence of diabetic ketoacidosis at diagnosis was highest in the 0-4-year-old age group. We predicted new cases of T1D will increase 1.57-fold over the next decade. CONCLUSIONS: T1D incidence in this large Chinese population is higher than has been reported previously. From 2007 to 2017, although the incidence peak was in the 10-14-year age group, the T1D incidence increased sharply in adults but not in youth.