Primary Defects in β-Cell Function Further Exacerbated by Worsening of Insulin Resistance Mark the Development of Impaired Glucose Tolerance in Obese Adolescents

OBJECTIVE—Impaired glucose tolerance (IGT) is a pre-diabetic state of increasing prevalence among obese adolescents. The purpose of this study was to determine the natural history of progression from normal glucose tolerance (NGT) to IGT in obese adolescents

Variants in the FFAR1 Gene Are Associated with Beta Cell Function

The FFAR1 receptor is expressed mainly in pancreatic beta cells and is activated by medium to long chain free fatty acids (FFAs), as well as by thiazolidinediones, resulting in elevated Ca(2+) concentrations and promotion of insulin secretion. These properties suggest that FFAR1 could be a mediator of lipotoxicity and a potential candidate gene for Type 2 diabetes (T2D). We therefore investigated whether variations at the FFAR1 locus are associated with T2D and beta cell function.We re-sequenced the FFAR1 region in 96 subjects (48 healthy and 48 T2D individuals) and found 13 single nucleotide polymorphisms (SNPs) 8 of which were not previously described. Two SNPs located in the upstream region of the FFAR1 gene (rs1978013 and rs1978014) were chosen and genotyped in 1929 patients with T2D and 1405 healthy control subjects. We observed an association of rs1978013 and rs1978014 with insulinogenic index in males (p = 0.024) and females (p = 0.032), respectively. After Bonferroni corrections, no association with T2D was found in the case-control material, however a haplotype consisting of the T-G alleles conferred protection against T2D (p = 0.0010).Variation in the FFAR1 gene may contribute to impaired beta cell function in T2D

New gravitational radiation experiments

Squared time derivatives of output powers of the Argonne and Maryland gravitational radiation detectors are written on magnetic tapes at Argonne and Maryland every 0.1 sec. A computer files the threshold crossing times. A coincidence is a pair of identical crossing times of both tapes. The accidentals rate is measured by repeating the procedure for a sequence of time delays in either channel. A significant excess of coincidences is found at zero delay. © 1973 The American Physical Society

New gravitational radiation experiments

Squared time derivatives of output powers of the Argonne and Maryland gravitational radiation detectors are written on magnetic tapes at Argonne and Maryland every 0.1 sec. A computer files the threshold crossing times. A coincidence is a pair of identical crossing times of both tapes. The accidentals rate is measured by repeating the procedure for a sequence of time delays in either channel. A significant excess of coincidences is found at zero delay. © 1973 The American Physical Society

New Gravitational Radiation Experiments

Squared time derivatives of output powers of the Argonne and Maryland gravitational radiation detectors are written on magnetic tapes at Argonne and Maryland every 0.1 sec. A computer files the threshold crossing times. A coincidence is a pair of identical crossing times of both tapes. The accidentals rate is measured by repeating the procedure for a sequence of time delays in either channel. A significant excess of coincidences is found at zero delay. © 1973 The American Physical Society

Leptin decreases apoptosis and alters BCL-2 : Bax ratio in clonal rodent pancreatic beta-cells.

AIMS/HYPOTHESIS: The adipocyte derived peptide hormone leptin is known to regulate apoptosis and cell viability in several cells and tissues, as well as having several pancreatic islet beta-cell specific effects such as inhibition of glucose-stimulated insulin secretion. This study investigated the effects of leptin upon apoptosis induced by serum depletion and on expression of the apoptotic regulators B-cell leukaemia 2 gene product (BCL-2) and BCL2-associated X protein (Bax) in the glucose-responsive BRIN-BD11 beta-cell line. METHODS: BRIN-BD11 cells were cultured in RPMI 1640 and subsequently serum depleted +/- leptin (10 and 50 ng/mL) for 24 h. Cell viability and apoptosis were measured using a modified MTS assay and TUNEL/YO-PRO-1 assays, respectively. BCL-2 and Bax expression were measured by real-time PCR and Western blotting. RESULTS: Leptin caused a reduction in serum-depleted apoptosis, although it failed to have any effect on the overall cell viability, causing a 68% shift from apoptosis to necrosis. Leptin significantly increased the level of BCL-2 mRNA expression (150% compared to serum depletion alone), without altering Bax mRNA expression. At the protein level, leptin increased BCL-2 and decreased Bax, altering the BCL-2 : Bax ratio. CONCLUSIONS: We conclude that leptin reduces apoptosis in beta-cells at physiological concentrations, possibly via its ability to up-regulate BCL-2 and Bax expression

Diabetes and Breast Cancer among Women with BRCA1 and BRCA2 Mutations

BACKGROUND:: Hyperinsulinemia and the metabolic syndrome are both risk factors for breast cancer. It is not clear if diabetes is associated with the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. METHODS:: The authors reviewed the medical histories of 6052 women with a BRCA1 or BRCA2 mutation, half of whom had been diagnosed with breast cancer. They estimated the odds ratio for breast cancer, given a self-report of diabetes. They then estimated the hazard ratio for a new diagnosis of diabetes associated with a history of breast cancer. RESULTS:: There was no excess of diabetes in the period before the diagnosis of breast cancer, compared with controls with no diagnosis of breast cancer. The risk of diabetes was doubled among BRCA carriers in the 15-year period after the diagnosis of breast cancer (relative risk, 2.0; 95% confidence interval [CI], 1.4-2.8; P = .0001), compared with carriers without cancer. The risk was particularly high for women with a body mass index (BMI) \u3e25.0 kg/m(2) (odds ratio, 5.8; 95% CI, 4.0-8.6; P = .0001). CONCLUSIONS:: After a diagnosis of breast cancer, women with a BRCA1 or BRCA2 mutation face a 2-fold increase in the risk of diabetes, which is exacerbated by a high BMI