Role of the sympathetic nervous system in regulation of the sodium glucose cotransporter 2.

BACKGROUND: The sympathetic nervous system (SNS) regulates glucose metabolism in various organs including the kidneys. The sodium glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in renal proximal tubules and its inhibition has been shown to improve glucose control, cardiovascular and renal outcomes. We hypothesized that SNS-induced alterations of glucose metabolism may be mediated via regulation of SGLT2. METHOD: We used human renal proximal tubule cells to investigate the effects of noradrenaline on SGLT2 regulation. Mice fed a high-fat diet were oral gavaged with dapagliflozin and the expression of noradrenaline and tyrosine hydroxylase was measured in the kidney and heart. RESULTS: Noradrenaline treatment resulted in a pronounced increase in SGLT2 and interleukin (IL)-6 expression in HK2 cells and promoted translocation of SGLT2 to the cell surface. In vivo, dapagliflozin treatment resulted in marked glucosuria in high-fat diet-fed mice. SGLT2 inhibition significantly reduced high-fat diet-induced elevations of tyrosine hydroxylase and noradrenaline in the kidney and heart. We also aimed to assess the levels of hypertension-related cytokines in the kidneys of our mice treated with and without dapagliflozin. Excitingly, we demonstrate that SGLT2 inhibition with dapagliflozin promoted a trend towards reduced tumour necrosis factor-alpha and elevated IL-1ß protein levels in the kidney. CONCLUSION: Our in-vitro and in-vivo studies provide first evidence for an important cross-talk between the SNS and SGLT2 regulation that may not only account for SNS-induced alterations of glucose metabolism but potentially contribute to cardiovascular and renal protection observed with SGLT2 inhibitors.

Inhaling Democracy: Cigarette Advertising and Health Education in Post-war West Germany, 1950s-1975.

In the late 1960s and early 1970s, the West German government was faced with the challenge of addressing a damaging health behaviour, smoking, in the context of an emerging late modern democracy, when the precedent for addressing that behaviour was set in the Nazi past. This paper details the two-pronged approach which the government took: seeking restrictions on cigarette advertising, whilst educating young people to adopt positive health behaviours in the face of pressure to smoke. This approach can be understood in the social and economic context of the time: an economic commitment to the social market economy worked against restrictions on the sale of cigarettes; whilst concerns about past authoritarian structures prompted the health authorities to seek novel ways of addressing smoking, emphasising choice. In a nuanced way, post-war anti-smoking strategies were a response to West Germany's National Socialist past, but more importantly, a signal of an increasingly international outlook.

Miscarriage, abortion or criminal feticide: understandings of early pregnancy loss in Britain, 1900-1950.

This paper explores the close links in medical understandings of miscarriage and abortion in the first half of the twentieth century in Britain. In the absence of a clear legal framework for abortion, and the secrecy surrounding the practice, medical literature suggests contradictory and confused views about women presenting with clinical signs of pregnancy loss. On one hand, there was a lack of clarity as to whether pregnancy loss was natural or induced, with a clear tendency to assume that symptoms of miscarriage were the result of criminal interference gone wrong. On the other hand, women who did not present for treatment when miscarriage was underway were accused of neglecting their unborn children. The paper suggests that discourses around pregnancy loss were class-based, distrustful of female patients, and shaped by the wider context of fertility decline and concerns about infant mortality. The close historical connection between miscarriage and abortion offers some insight into why both the pro-life movement and miscarriage support advocates today draw on similar imagery and rhetoric about early fetal loss.

From youth protection to individual responsibility: addressing smoking among young people in post-war West Germany.

This article draws on health education material produced on smoking in the 1950s and 1960s in West Germany to question the extent to which smoking and health disappeared from the agenda in the post war decades, following the experience of anti-smoking propaganda during the Third Reich. It suggests that continuities can be seen in anti-smoking literature and campaigns both before and after the Third Reich around the notion of youth protection. In the early 1960s, there was a more decisive break with the past with the foundation of the Ministry of Health and a growing determination to make health education a federal responsibility. There was an evident shift towards notions of individual responsibility and rational choice, informed by a growing body of international epidemiological evidence on smoking and health. There were also some attempts to engage with youth culture in the 1960s, rather than seeing youth culture as a threat to the social order, as had been the case in older youth protection arguments against smoking.

An early experiment in national identity cards: the battle over registration in the First World War.

The current debate on issuing identity cards to the British population was foreshadowed during the First World War, when the National Registration Act of 1915 provided for a register of all men and women between 15 and 65, later used to aid conscription. The National Register was produced by Bernard Mallet, the Registrar General of England and Wales. The information demands of the war also provided an opportunity for Mallet to press forward his pre-war agenda of reforming the system of routine registration of births, marriages and deaths. His desire for reform was shaped by the pressing eugenic questions of the day - infant mortality and national efficiency - and as the war progressed, he developed his ideas to include a permanent universal register of all individuals. This article examines the fate of Mallet's proposals, and shows how lack of political consensus and lack of support, even from colleagues in the General Register Office for Scotland, prevented his proposals coming to fruition.

The nature and identification of quantitative trait loci: a community's view.

This white paper by eighty members of the Complex Trait Consortium presents a community's view on the approaches and statistical analyses that are needed for the identification of genetic loci that determine quantitative traits. Quantitative trait loci (QTLs) can be identified in several ways, but is there a definitive test of whether a candidate locus actually corresponds to a specific QTL?