Sex and muscle structural lipids in obese subjects - an impact on insulin action?

Background Long-chain polyunsaturated fatty acid (LCPUFA) especially the n-3-FA of skeletal muscle phospholipids may facilitate insulin action, whereas saturated and trans-FA act oppositely. Community studies show that non-diabetic weight matched obese men and women display similar insulin resistance, despite the fact that an android fat distribution is detrimental to insulin action. The increased extramyocellular fat mass of obese women may act in a paracrine manner such that its release of free FA and cytokines may hamper in situ desaturation and elongation of FA in skeletal muscle phospholipids. Material and methods To test the hypothesis that obese women may display an inferior FA composition compared to obese men, the FA composition of skeletal muscle phospholipids was determined in vastus lateralis biopsies obtained from 12 non-diabetic obese women with a typical gynoid fat distribution, nine non-diabetic obese men with a typical android fat distribution and 12 (seven females) lean age matched healthy controls (body mass index 34.6 +/- 1.0 kg m(-2), 36.5 +/- 1.2 and 22.5 +/- 0.5; age 47 +/- 2 years, 51 +/- 3 and 49 +/- 2). Results Obese women displayed decreased LCPUFA n-3 and ratio of n-3/n-6 PUFA, whereas trans-FA and palmitic-FA (C16 : 0) were increased compared to obese men and controls (all Ps < 0.05). Plasma high-density lipoprotein cholesterol (HDL-C), triglycerides and a marker of insulin sensitivity were similar between obese women and men but impaired compared to controls (Ps < 0.05). Conclusions The data support the hypothesis that insulin resistant non-diabetic obese men display a more optimal skeletal muscle phospholipid FA composition than their female counterparts, which may be a mechanism to compensate the detrimental effect on insulin action of an android fat distribution

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Somatostatin inhibits exocytosis in rat pancreatic alpha-cells by G(i2)-dependent activation of calcineurin and depriming of secretory granules.

1. Measurements of cell capacitance were used to investigate the molecular mechanisms by which somatostatin inhibits Ca(2+)-induced exocytosis in single rat glucagon-secreting pancreatic alpha-cells. 2. Somatostatin decreased the exocytotic responses elicited by voltage-clamp depolarisations by 80 % in the presence of cyclic AMP-elevating agents such as isoprenaline and forskolin. Inhibition was time dependent and half-maximal within 22 s. 3. The inhibitory action of somatostatin was concentration dependent with an IC(50) of 68 nM and prevented by pretreatment of the cells with pertussis toxin. The latter effect was mimicked by intracellular dialysis with specific antibodies to G(i1/2) and by antisense oligonucleotides against G proteins of the subtype G(i2). 4. Somatostatin lacked inhibitory action when applied in the absence of forskolin or in the presence of the L-type Ca(2+) channel blocker nifedipine. The size of the omega-conotoxin-sensitive and forskolin-independent component of exocytosis was limited to 60 fF. By contrast, somatostatin abolished L-type Ca(2+) channel-dependent exocytosis in alpha-cells exposed to forskolin. The magnitude of the latter pool amounted to 230 fF. 5. The inhibitory effect of somatostatin on exocytosis was mediated by activation of the serine/threonine protein phosphatase calcineurin and was prevented by pretreatment with cyclosporin A and deltamethrin or intracellularly applied calcineurin autoinhibitory peptide. Experiments using the stable ATP analogue AMP-PCP indicate that somatostatin acts by depriming of granules. 6. We propose that somatostatin receptors associate with L-type Ca(2+) channels and couple to G(i2) proteins leading to a localised activation of calcineurin and depriming of secretory granules situated close to the L-type Ca(2+) channels

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A new hearing aid system is provided that includes geographical position and user feedback in determining the category of the sound environment for automatic adjustment of signal processing parameters

Learning hearing aid

A new hearing aid system is provided that includes geographical position and user feedback in determining the category of the sound environment for automatic adjustment of signal processing parameters