Increased SGLT1 expression in salivary gland ductal cells correlates with hyposalivation in diabetic and hypertensive rats

Background Oral health complications in diabetes and hypertension include decreased salivary secretion. The sodium-glucose cotransporter 1 (SGLT1) protein, which transports 1 glucose/2 Na+/264 H2O molecules, is described in salivary glands. We hypothesized that changes in SGLT1 expression in the luminal membrane of ductal cell may be related to an altered salivary flow. Findings By immunohistochemistry, we investigated SGLT1 expression in ductal cells of parotid and submandibular glands from Wistar Kyoto rats (WKY), diabetic WKY (WKY-D), spontaneously hypertensive rats (SHR) and diabetic SHR (SHR-D), as well as in parotid glands from WKY subjected to sympathetic stimulation, with or without previous propranolol blockade. Diabetes and hypertension decreased the salivary secretion and increased SGLT1 expression in the luminal membrane of ductal cells, and their association exacerbated the regulations observed. After 30 min of sympathetic stimulation, SGLT1 increased in the luminal membrane of ductal cells, and that was blocked by previous injection of propranolol. Conclusions SGLT1 expression increases in the luminal membrane of salivary gland ductal cells and the salivary flow decreases in diabetic and hypertensive rats, which may be related to sympathetic activity. This study highlights the water transporter role of SGLT1 in salivary glands, which, by increasing ductal water reabsorption, may explain the hyposalivation of diabetic and hypertensive subjects

Ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women with polycystic ovary syndrome

Objective To evaluate whether the presence of polycystic ovary syndrome (PCOS) alters multiple ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women without any other health condition that could interfere with combined oral contraceptive (COC) eligibility criteria. Methods This was a case- control study evaluating 90 obese women ( body mass index ( BMI) = 30.0 kg/m2 and < 40 kg/m2) aged between 18 and 40 years without any other health condition that could interfere with COC eligibility criteria, of whom 45 had PCOS and 45 were age- matched controls. BMI, waist and hip circumference, arterial blood pressure, fasting insulin and glucose, quantitative insulin sensitivity check index ( QUICKI), highdensity lipoprotein cholesterol, low- density lipoprotein cholesterol, total cholesterol, triglycerides, testosterone, sex hormone- binding globulin, free androgen index ( FAI), carotid stiffness index, intima media thickness, flowmediated dilatation ( FMD) of the brachial artery and non- alcoholic fatty liver disease ( NAFLD) were assessed. Results In women with PCOS, we observed a higher frequency of NAFLD ( 73.3 vs. 46.7%, P < 0.01) and higher FAI ( 10.4 vs. 6.8%, P < 0.01). We also observed a trend towards increased insulin levels ( 10.06 +/- 6.66 vs. 7.45 +/- 5.88 mu IU/mL, P = 0.05), decreased QUICKI ( 0.36 +/- 0.06 vs. 0.39 +/- 0.07, P = 0.05) and decreased FMD ( 7.00 +/- 3.87 vs. 8.41 +/- 3.79%, P = 0.08). No other significant difference was observed. Conclusions NAFLD is frequent in obese women without any other health condition that could interfere with COC eligibility criteria, especially in those with PCOS. This should be considered when choosing the best contraceptive option. Copyright (C) 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Cellular interference in craniofrontonasal syndrome: males mosaic for mutations in the X-linked EFNB1 gene are more severely affected than true hemizygotes

Craniofrontonasal syndrome (CFNS), an X-linked disorder caused by loss-of-function mutations of EFNB1, exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis and additional minor malformations, but males are usually more mildly affected with hypertelorism as the only feature. X-inactivation is proposed to explain the more severe outcome in heterozygous females, as this leads to functional mosaicism for cells with differing expression of EPHRIN-B1, generating abnormal tissue boundaries-a process that cannot occur in hemizygous males. Apparently challenging this model, males occasionally present with a more severe female-like CFNS phenotype. We hypothesized that such individuals might be mosaic for EFNB1 mutations and investigated this possibility in multiple tissue samples from six sporadically presenting males. Using denaturing high performance liquid chromatography, massively parallel sequencing and multiplex-ligation-dependent probe amplification (MLPA) to increase sensitivity above standard dideoxy sequencing, we identified mosaic mutations of EFNB1 in all cases, comprising three missense changes, two gene deletions and a novel point mutation within the 5' untranslated region (UTR). Quantification by Pyrosequencing and MLPA demonstrated levels of mutant cells between 15 and 69%. The 5' UTR variant mutates the stop codon of a small upstream open reading frame that, using a dual-luciferase reporter construct, was demonstrated to exacerbate interference with translation of the wild-type protein. These results demonstrate a more severe outcome in mosaic than in constitutionally deficient males in an X-linked dominant disorder and provide further support for the cellular interference mechanism, normally related to X-inactivation in females.