The mitochondrial DNAs (mtDNAs) from individuals belonging to three Chilean tribes, the Mapuche, the Pehuenche, and the Yaghan, were studied both by RFLP analysis and D-loop (control region) sequencing. RFLP analysis showed that 3 individuals (1.3%) belonged to haplogroup A, 19 (8%) to haplogroup B, 102 (43%) to haplogroup C, and 113 (47.7%) to haplogroup D. Among the 73 individuals analyzed by D-loop sequencing, we observed 37 different haplotypes defined by 52 polymorphic sites. Joint analysis of data obtained by RFLP and sequencing methods demonstrated that, regardless of the method of analysis, the mtDNA haplotypes of these three contemporary South American aborigine groups clustered into four main haplogroups, in a way similar to those previously described for other Amerindians. These results further revealed the absence of haplogroup A in both the Mapuche and Yaghan as well as the absence of haplogroup B in the Yaghan. These results suggest that the people of Tierra del Fuego are related to tribes from south-central South America.

Artículo de publicación ISIRationale: The ability of a cell to independently regulate nuclear and cytosolic Ca2+ signaling is currently attributed to the differential distribution of inositol 1,4,5-trisphosphate receptor channel isoforms in the nucleoplasmic versus the endoplasmic reticulum. In cardiac myocytes, T-tubules confer the necessary compartmentation of Ca2+ signals, which allows sarcomere contraction in response to plasma membrane depolarization, but whether there is a similar structure tunneling extracellular stimulation to control nuclear Ca2+ signals locally has not been explored. Objective: To study the role of perinuclear sarcolemma in selective nuclear Ca2+ signaling. Methods and Results: We report here that insulin-like growth factor 1 triggers a fast and independent nuclear Ca2+ signal in neonatal rat cardiac myocytes, human embryonic cardiac myocytes, and adult rat cardiac myocytes. This fast and localized response is achieved by activation of insulin-like growth factor 1 receptor signaling complexes present in perinuclear invaginations of the plasma membrane. The perinuclear insulin-like growth factor 1 receptor pool connects extracellular stimulation to local activation of nuclear Ca2+ signaling and transcriptional upregulation through the perinuclear hydrolysis of phosphatidylinositol 4,5-biphosphate inositol 1,4,5-trisphosphate production, nuclear Ca2+ release, and activation of the transcription factor myocyte-enhancing factor 2C. Genetically engineered Ca2+ buffers—parvalbumin—with cytosolic or nuclear localization demonstrated that the nuclear Ca2+ handling system is physically and functionally segregated from the cytosolic Ca2+ signaling machinery. Conclusions: These data reveal the existence of an inositol 1,4,5-trisphosphate–dependent nuclear Ca2+ toolkit located in direct apposition to the cell surface, which allows the local control of rapid and independent activation of nuclear Ca2+ signaling in response to an extracellular ligan

ROSA, GIUSEPPINA, PAOLA DI ROCCO, MELANIA MANCO, ALDO V. GRECO, MARCO CASTAGNETO, HUBERT VIDAL, AND GELTRUDE MINGRONE. Reduced PDK4 expression associates with increased insulin sensitivity in postobese patients. Obes Res. 2003;11: 176 -182. Objective: The aim of this study was to verify whether changes in PDK4 mRNA expression in skeletal muscle in formerly obese subjects who underwent malabsorptive bariatric surgery [bilio-pancreatic diversion (BPD)] might be related to insulin sensitivity improvement, and if these possible modifications might correlate with a reduction of the intramyocytic lipid level. Research Methods and Procedures: Six obese women (body mass index 46.6 Ϯ 8.2 kg/m 2 ) were enrolled in the study. Body composition, euglycemic-hyperinsulinemic clamp and muscle biopsies for skeletal muscle lipid analysis, and semiquantitative reverse transcriptase-polymerase chain reaction were performed before and 3 years after BPD. Results: The average weight loss observed after surgery was ϳ42%. Increased glucose uptake was accompanied by a significant decrease of PDK4 mRNA (R 2 ϭ 0.71, p Ͻ 0.001). The amounts of intramyocytic triglycerides correlate directly with PDK4 mRNA (R 2 ϭ 0.87, p ϭ 0.005) and inversely with glucose uptake values (R 2 ϭ 0.75, p Ͻ 0.001). Discussion:Our results support the concept that a reduced tissue availability of fatty acids consequent to a massive lipid malabsorption influences glucose metabolism acting through the regulation of PDH complex. In fact, as shown in animals, a higher level of FFA availability is likely to induce overexpression of PDK4 also in humans.

AIMS=HYPOTHESIS:The aim of the present study was to investigate the relationship between intramyocytic triglycerides levels, muscle TNF-a and GLUT4 expression and insulin resistance. METHODS: Insulin sensitivity was studied in 14 severely obese women (BMI > 40 kg=m 2 ), before and 6 months after low-dietary intake or bariatric malabsorptive surgery (bilio-pancreatic diversion, BPD), by the euglycaemic hyperinsulinaemic clamp technique, while the amount of intramyocytic triglycerides was chemically measured in needle muscle biopsies. Using reverse transcriptase-polymerase chain reaction analysis, the muscle mRNA expression of TNF-a and GLUT4 was also investigated. RESULTS: The weight loss after surgery was 25.98 AE 5.81 kg (P < 0.001), while that obtained with the diet was 5.07 AE 5.99 kg (P ¼ NS). Marked decrease in TNF-a mRNA levels (76.67 AE 12.59 to 14.01 AE 5.21 AU, P < 0.001) were observed in comparison with pre-treatment, whereas GLUT4 was significantly increased (62.25 AE 11.77 -124.25 AE 21.01 AU, P < 0.001) only in BPD patients. Increased glucose uptake (M) was accompanied by a significant decrease of TNF-a mRNA (76.67 AE 12.59 -14.01 AE 5.21 AU, P < 0.01) and an increase of GLUT4. The amounts of TNF-a mRNAs in skeletal muscle correlated inversely with GLUT4 mRNAs and directly with intramyocytic triglycerides levels. In a step-down regression analysis (r 2 ¼ 0.95) TNFa mRNA (P ¼ 0.0014), muscular TG levels (P ¼ 0.018), and GLUT4 mRNA (P ¼ 0.028) resulted to be the most powerful independent variables for predicting M values. CONCLUSION=INTERPRETATION: These findings suggest that insulin resistance in morbidly obese patients is positively associated to the intramyocytic triglycerides content and to TNF-a gene expression and inversely correlated to GLUT4 expression.