Stanniocalcin-1 in the subfornical organ inhibits the dipsogenic response to angiotensin II.

Recently, receptors for the calcium-regulating glycoprotein hormone stanniocalcin-1 (STC-1) have been found within subfornical organ (SFO), a central structure involved in the regulation of electrolyte and body fluid homeostasis. However, whether SFO neurons produce STC-1 and how STC-1 may function in fluid homeostasis are not known. Two series of experiments were done in Sprague-Dawley rats to investigate whether STC-1 is expressed within SFO and whether it exerts an effect on water intake. In the first series, experiments were done to determine whether STC-1 was expressed within cells in SFO using immunohistochemistry, and whether protein and gene expression for STC-1 existed in SFO using Western blot and quantitative RT-PCR, respectively. Cells containing STC-1 immunoreactivity were found throughout the rostrocaudal extent of SFO. STC-1 protein expression within SFO was confirmed with Western blot, and SFO was also found to express STC-1 mRNA. In the second series, microinjections (200 nl) of STC-1, ANG II, a combination of the two or the vehicle were made into SFO in conscious, unrestrained rats. Water intake was measured at 0700 for a 1-h period after each injection in animals. Microinjections of STC-1 (17.6 or 176 nM) alone had no effect on water intake compared with controls. However, STC-1 not only attenuated the drinking responses to ANG II for about 30 min, but also decreased the total water intake over the 1-h period. These data suggest that STC-1 within the SFO may act in a paracrine/autocrine manner to modulate the neuronal responses to blood-borne ANG II. These findings also provide the first direct evidence of a physiological role for STC-1 in central regulation of body fluid homeostasis.

Stanniocalcin-1 co-localizes with insulin in the pancreatic islets.

The polypeptide hormone stanniocalcin-1 (STC-1) is widely expressed in mammals and signals both locally and systemically. In many tissues STC-1 ligand is sequestered by target cell organelles (mitochondria, nuclei, and cholesterol lipid droplets) to exert diverse biological effects. Most notably, STC-1 serves as an uncoupler of oxidative phosphorylation in liver, muscle, and kidney mitochondria. The present paper describes the identification of STC-1 receptors in mouse pancreatic ß cells and the discovery that the ligand co-localizes with insulin in pancreatic ß cells. In situ hybridization (ISH) analysis subsequently revealed that pancreatic ß cells were the source of the ligand. Intriguingly however, all ISH signal was localized over putative islet cell nuclei as opposed to the cell cytoplasm. Real-time qPCR and agarose gel electrophoresis revealed that the STC-1 amplicon generated from islet cell total RNA was the same size as that from kidney. However, relative levels of STC-1 gene expression were >100-fold lower in islets than those in kidney tissue. Collectively, these findings are indicative of a local STC-1 signalling pathway in pancreatic ß cells. The role of STC-1 in this context remains to be established, but it could very well entail the regulation of ß cell mitochondria membrane potential which is an integral aspect of regulated insulin release. Interestingly, STC-1 immunoreactivity was not evident in embryonic pancreatic islets, suggesting that ligand synthesis may only commence postnatally.

Incidence and presentation of reported coeliac disease in Cardiff and the Vale of Glamorgan: the next 10 years.

OBJECTIVE: To determine whether there is a continued increase in the incidence of coeliac disease (CD) in the population of Cardiff and the Vale of Glamorgan between 1996 and 2005 compared with previous data for 1981-1995, and to describe the presenting features during this time. DESIGN: Retrospective case-finding study using pathology, dietetic and clinical records held in hospitals and general practice within Cardiff and the Vale of Glamorgan. All local consultants including those at private hospitals were contacted. Incidence rates were calculated using the Welsh Assembly Government's mid-year estimates. RESULTS: In total, 347 newly diagnosed cases of CD (42 children, 305 adults) were detected. Compared with previous published data, incidence rates in adults per 100 000 have increased from 3.08 at the end of 1995 to 11.13 in 2005. In children, the disease incidence has trebled to 6.89 per 100 000. There have been some changes in presenting symptoms, with a marked preponderance of abdominal pain and bloating in women (P<0.05). There has been a 14-fold increase in the numbers of patients undergoing coeliac serology testing from 1996 to 2005, associated with an increased absolute number of new cases. However, the proportion of new cases diagnosed compared with numbers of serological tests performed decreased from 5.8 to 1.1%. CONCLUSION: The incidence of CD in children and adults has markedly increased. One of the most striking features of our data in adult CD is the increasing frequency of abdominal pain and bloating in the female cohort. Incorporation of antibody testing into clinical guidelines is likely to result in a wider spectrum of individuals with nonspecific gastrointestinal symptoms being investigated and diagnosed with CD in the future.