Rosiglitazone decreases intra- to extramyocellular fat ratio in obese non-diabetic adults with metabolic syndrome

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background Insulin resistance is intrinsically related to intramyocellular (IMCL) rather than extramyocellular (EMCL) triglyceride content. Conflicting results have been reported on the ability of insulin sensitizer agents, such as thiazolidinediones, to modify muscle fat distribution. The aim of this study was to investigate the role of rosiglitazone on muscle fat compartment distribution in an adult population of obese non-diabetic metabolic syndrome patients. Patients and methods Fifteen obese, non-diabetic, metabolic syndrome patients were studied by means of proton nuclear magnetic resonance ((1)H-NMR) spectroscopy before and after treatment with rosiglitazone 8 mg/day for 6 months. Anthropometrical and metabolic variables were assessed. Results After rosiglitazone, body weight and hip circumference increased [100.9 (91.12-138.7) vs. 107.0 (79.6-142.8) kg and 118 (107-126) vs. 122 (110-131) cm]; while waist-hip ratio (WHR) decreased from 0.93 (0.87-1.00) to 0.89 (0.82-0.97) (P < 0.001 for all). Additionally, fasting plasma glucose, insulin and homeostatis model assessment of insulin resistance (HOMA-IR) significantly decreased while adiponectin increased over threefold [9.7 (3.7-17.7) vs. 38.0 (19.3-42.4) mu g/ml] without any changes in resistin. Finally, the IMCL did not change [267.54 (213.94-297.94) vs. 305.75 (230.80-424.75) arbitrary units (AU), P = 0.15] while the EMCL increased [275.53 (210.39-436.66) vs. 411.39 (279.92-556.59) AU; P < 0.01] therefore decreasing the IMCL-to-EMCL (IMCL/EMCL) ratio [1.07 (0.78-1.23) vs. 0.71 (0.53-0.96); P < 0.01]. Conclusion Rosiglitazone treatment increased body weight and hip circumference and decreased WHR. More importantly, it decreased the IMCL/EMCL ratio by increasing the EMCL without any significant change on the IMCL.2712329Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Research Supporting Agency of Rio de Janeiro State [E-26/150.141/99, E-26/170.522/00]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq [CNPq 52 1850/96-7]Research Supporting Agency of Rio de Janeiro State [E-26/150.141/99, E-26/170.522/00

Metformin improves skin capillary reactivity in normoglycaemic subjects with the metabolic syndrome

WSTĘP. Insulinooporność i rodzinne występowanie cukrzycy niezależnie wiążą się z dysfunkcją śródbłonka. Stres oksydacyjny odgrywa kluczową rolę w patofizjologii uszkodzenia naczyń krwionośnych. Metformina, oprócz obniżania stężenia glukozy, działa ochronnie na naczynia. Celem niniejszej pracy by&#179;o zbadanie, czy metformina korzystnie wpływa na krążenie w odżywczych naczyniach włosowatych skóry oraz czy zmniejsza stres oksydacyjny u osób wysokiego ryzyka wystąpienia cukrzycy typu 2 i chorób sercowo-naczyniowych. METODY. Badaniem objęto 30 pacjentów z prawidłowym stężeniem glukozy i zespołem metabolicznym (MS), którzy mieli krewnych chorych na cukrzycę typu 2. średni wiek wynosił 39,1 &#177; 8,4 roku, a wskaźnik masy ciała (BMI) 35,8 &#177; 4,8 kg/m2 (średnia &#177; odchylenie standardowe). Pacjentów losowo podzielono na 2 grupy za pomocą metody podwójnie &#156;lepej próby w stosunku 1:1 - 14 osób otrzymywało placebo, a 16 metforminę (1700 mg/d.). Wyjściowo i po zakończeniu badania pobrano krew do analizy biochemicznej oraz mocz w celu określenia stężenia 8-epi-prostaglandyny F2&#945; (8-epi-PGF2&#945;). Krążenie w naczyniach włosowatych oceniano za pomocą wideokapilaroskopii obrąbka naskórkowego, podczas której analizowano średnicę pętli naczyń włosowatych doprowadzających (AF), odprowadzających (EF) i wierzchołkowych (AP), funkcjonalną gęstość naczyń włosowatych (FCD), prędkość przepływu czerwonych ciałek krwi w spoczynku (RBCV) oraz po 1 minucie od okluzji naczyń tętniczych (RBCVmax), a także czas potrzebny do jej osiągnięcia (TRBCVmax). WNIOSKI. Metformina poprawiła reaktywność naczyń włosowatych skóry u osób z prawidłową glikemią i zespołem metabolicznym, niezależnie od zmian stężenia 8-epi-PGF2&#945;.AIMS. Insulin resistance and a parental history of diabetes mellitus are independently associated with endothelial dysfunction. Oxidative stress has a pivotal role in the pathophysiology of vascular injury. Metformin, in addition to its glucose-lowering properties, has vasculoprotective effects. We investigated whether metformin has beneficial effects on the nutritive skin capillary circulation and deceases oxidative stress in a group at high risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. METHODS. Thirty normoglycaemic subjects with the metabolic syndrome (MS), who had first-degree relatives with T2DM, participated. The mean age was 39.1 &#177; 8.4 years and body mass index (BMI) 35.7 &#177; &#177; 4.8 kg/m2 (mean &#177; SD). Subjects were randomized 1:1 to receive placebo (n = 14) or metformin (n = 16; 1700 mg/day) in a double-blind study. At baseline and post treatment, blood and urine samples were collected for biochemical and 8-epi-prostaglandin F2&#945; (8-epi-PGF2&#945;) analysis, respectively. Microcirculation was assessed by nailfold videocapillaroscopy, analysing afferent (AF), efferent (EF) and apical (AP) diameters of capillary loops, functional capillary density (FCD), red blood cell velocity at rest (RBCV), after 1 min arterial occlusion (RBCVmax) and time (TRBCVmax) taken to reach it. RESULTS. Groups did not differ significantly in anthropometric, clinical, laboratory or microvascular measurements at baseline. In the metformin group, weight, BMI, systolic blood pressure and fasting plasma glucose fell, and lipid profile and microcirculatory parameters FCD, AF, EF, AP, RBCVmax and TRBCVmax improved (all p < 0.01). No relationship between clinico-laboratory parameters and microvascular reactivity was observed, except for changes in total and lowdensity lipoprotein-cholesterol and RBCVmax. 8-epi-PGF2&#945; did not change significantly in either group. CONCLUSIONS. Metformin improved skin capillary reactivity in normoglycaemic MS subjects independently of significant changes in 8-epi-PGF2&#945; levels

Vasomotion and Neurovascular Coupling in the Visual Thalamus In Vivo

Spontaneous contraction and relaxation of arteries (and in some instances venules) has been termed vasomotion and has been observed in an extensive variety of tissues and species. However, its functions and underlying mechanisms are still under discussion. We demonstrate that in vivo spectrophotometry, measured simultaneously with extracellular recordings at the same locations in the visual thalamus of the cat, reveals vasomotion, measured as an oscillation (0.14hz) in the recorded oxyhemoglobin (OxyHb) signal, which appears spontaneously in the microcirculation and can last for periods of hours. During some non-oscillatory periods, maintained sensory stimulation evokes vasomotion lasting ∼30s, resembling an adaptive vascular phenomenon. This oscillation in the oxyhaemoblobin signal is sensitive to pharmacological manipulation: it is inducible by chloralose anaesthesia and it can be temporarily blocked by systemic administration of adrenaline or acetylcholine (ACh). During these oscillatory periods, neurovascular coupling (i.e. the relationship between local neural activity and the rate of blood supply to that location) appears significantly altered. This raises important questions with regard to the interpretation of results from studies currently dependent upon a linear relationship between neural activity and blood flow, such as neuroimaging