Rosa T. Fukui

Differential regulation of PGC-1α expression in rat liver and skeletal muscle in response to voluntary running

BackgroundThe beneficial actions of exercise training on lipid, glucose and energy metabolism and insulin sensitivity appear to be in part mediated by PGC-1α. Previous studies have shown that spontaneously exercised rats show at rest enhanced responsiveness to exogenous insulin, lower plasma insulin levels and increased skeletal muscle insulin sensitivity. This study was initiated to examine the functional interaction between exercise-induced modulation of skeletal muscle and liver PGC-1α protein expression, whole body insulin sensitivity, and circulating FFA levels as a measure of whole body fatty acid (lipid) metabolism.MethodsTwo groups of male Wistar rats (2 Mo of age, 188.82 ± 2.77 g BW) were used in this study. One group consisted of control rats placed in standard laboratory cages. Exercising rats were housed individually in cages equipped with running wheels and allowed to run at their own pace for 5 weeks. At the end of exercise training, insulin sensitivity was evaluated by comparing steady-state plasma glucose (SSPG) concentrations at constant plasma insulin levels attained during the continuous infusion of glucose and insulin to each experimental group. Subsequently, soleus and plantaris muscle and liver samples were collected and quantified for PGC-1α protein expression by Western blotting. Collected blood samples were analyzed for glucose, insulin and FFA concentrations.ResultsRats housed in the exercise wheel cages demonstrated almost linear increases in running activity with advancing time reaching to maximum value around 4 weeks. On an average, the rats ran a mean (Mean ± SE) of 4.102 ± 0.747 km/day and consumed significantly more food as compared to sedentary controls (P < 0.001) in order to meet their increased caloric requirement. Mean plasma insulin (P < 0.001) and FFA (P < 0.006) concentrations were lower in the exercise-trained rats as compared to sedentary controls. Mean steady state plasma insulin (SSPI) and glucose (SSPG) concentrations were not significantly different in sedentary control rats as compared to exercise-trained animals. Plantaris PGC-1α protein expression increased significantly from a 1.11 ± 0.12 in the sedentary rats to 1.74 ± 0.09 in exercising rats (P < 0.001). However, exercise had no effect on PGC-1α protein content in either soleus muscle or liver tissue. These results indicate that exercise training selectively up regulates the PGC-1α protein expression in high-oxidative fast skeletal muscle type such as plantaris muscle.ConclusionThese data suggest that PGC-1α most likely plays a restricted role in exercise-mediated improvements in insulin resistance (sensitivity) and lowering of circulating FFA levels.

Insulin resistance in limb and trunk partial lipodystrophy (type 2 Köbberling-Dunnigan syndrome)

We studied insulin action in two patients with limb and trunk partial lipodystrophy with hirsutism and acanthosis nigricans. Glucose was normal in one of the patients and slightly above normal in the other during an oral glucose tolerance test (OGTT). An intravenous glucose tolerance test (IVGTT) was normal in both patients. Basal and glucose-stimulated insulin levels were elevated in both the OGTT and IVGTT in both patients. The response of plasma glucose to exogenously administered insulin was decreased. A euglycemic-hyperinsulinemic clamp performed in patient no. 2 indicated insulin resistance, which was not corrected by reducing the increased basal level of serum free fatty acids (FFAs). Binding of insulin to neck adipocytes was normal in both subjects, but glucose transport and oxidation in these cells was impaired. Insulin binding to abdominal adipocytes was increased in one patient whose adipocytes displayed higher glucose transport at low insulin concentrations. Glucose oxidation was decreased in abdominal adipocytes of both patients. We conclude that insulin resistance in Köbberling-Dunnigan type 2 partial lipodystrophy is not related to an alteration of the insulin molecule or to changes in insulin binding, but is more likely associated with a postreceptor defect, since glucose oxidation was impaired in adipocytes of the neck and abdomen.

Acanthosis nigricans em mulheres obesas de uma população miscigenada: um marcador de distúrbios metabólicos

< 0,01), mais obesas (41 ± 6 versus 39 ± 6 kg/m 2 , p<0.01), tinham maior circunferencia de cintura, maior frequencia de obesidade androide, de diabetes tipo 2 (11,1% versus 4,3%, p=0,05), maiores niveis de insulina de jejum e de resistencia insulina (Homa IR) do que aquelas sem AN. As frequencias de hipertensao diastolica e alteracoes do colesterol total e fracoes e de triglicerides entre os grupos foram similares. C ONCLUSAO - Em mulheres obesas de uma populacao miscigenada, AN foi mais frequente nas de raca negra e parda e foi observada maior frequencia de co-morbidades da sindrome metabolica em comparacao a populacao sem AN. As mulheres obesas com AN devem ser investigadas para disturbios metabolicos, mesmo sendo jovens. Palavras-chaves: Acantose nigricans; diabetes mellitus nao insulino-dependente; metabolismo; obesidade; racas; resistencia a insulina. Summary: BACKGROUND - Acanthosis nigricans (AN) has been associated with various metabolic and endocrine disturbances. O BJECTIVE: The objective of this study is to evaluate the frequency of metabolic syndrome clusters in a group of obese mixed-race women with

Carbohydrate beverages attenuate bone resorption markers in elite runners

OBJECTIVE We evaluated the effects of carbohydrate (CHO) supplementation on markers of bone turnover in elite runners. DESIGN Twenty-four male runners were randomly assigned to two groups--a CHO and a control (CON) group--using a double-blind design. The participants were submitted to an overload training program (days 1-8), followed by a high-intensity intermittent running protocol (10×800 m) on day 9. They received a maltodextrin solution (CHO group) or a placebo solution as the CON equivalent, before, during, and after these protocols. RESULTS After 8 days of intensive training, baseline levels of osteocalcin (OC) decreased in both CHO and CON groups (before: 28.8±3.6 and 26.6±2.4 ng/ml, after: 24.8±3.0 and 21.9±1.6 ng/ml, respectively, p<0.01). On day 9, at 80 min of the recovery period, carboxy-terminal of telopeptide type I collagen (CTX) serum concentration was suppressed in the CHO group (0.3±0.1 ng/ml) vs. 0.6±0.0 ng/ml for the CON group (p<0.01). CHO supplementation was effective in decreasing CTX levels from baseline to recovery (0.5±0.1 ng/mL to 0.3±0.1 ng/mL, p<0.001), while an increase from 0.4±0.0 ng/mL to 0.6±0.0 ng/mL (p<0.001) was observed in the CON group. CONCLUSION CHO beverage ingestion attenuated the exercise-induced increase in CTX concentration, suggesting that CHO supplementation is a potential strategy to prevent bone damage in athletes.

Diabetes autoimune em adultos: características clínicas e autoanticorpos

The prevalence of anti-insulin (IAA), anti-glutamic acid decarboxylase 65 (anti-GAD) and anti-islet cell antibodies (ICA) and the clinical and metabolic findings of 66 patients with adult-onset diabetes mellitus (DM) manifested at 47.2±11.6 years with known duration of 14.3±8.4y were determined. RESULTS: ICA was positive in 10 cases (10 to 640 JDF U), 3 of them being also positive for anti-GAD (15.6 to 113.5 U/ml) and one for IAA (in those without previous insulin therapy). 15.2% of the patients had one or more autoantibodies, with greater prevalence for ICA. There were no differences between patients with and without autoantibodies for clinical DM presentation and prevalence of chronic complications. Only the cholesterol levels were lower in the antibody positive group (205.2±49.6 vs. 247.1±61.3mg/dl; p<0.05). CONCLUSION: 15.2% of the adult-onset DM had one or more autoantibodies, with greater prevalence for ICA. Autoantibodies determination is necessary for the diagnosis of autoimmune DM.

Association of interleukin 21 receptor gene variants with autoimune diseases in a type 1 diabetes cohort

Background Type 1 Diabetes (T1D) is an autoimmune disorder mediated by T lymphocytes and dendritic cells. The lymphocyte activation involves the inflammatory pathways T helper1 (Th1), Th2 and Th17 and the inhibition of regulatory T cells. It was found that Th17 pathway is implicated in the inflammatory process termed insulitis, resulting in the destruction of pancreatic beta cells, being regulated by the interleukins IL-21, IL-23 and IL-27. Studies have demonstrated a role for the interation of IL21 and its receptor IL21R in the genesis and progression of many autoimmune diseases. The variant rs2214537 was associated with multiple sclerosis and Kawasaki disease and rs2285452 with thyroid disease.