Helicity-dependent generalized parton distributions for nonzero skewness

We investigate the helicity dependent generalized parton distributions (GPDs) in momentum as well as transverse position (impact) spaces for up and down quarks in a proton when the momentum transfer in both the transverse and longitudinal directions are nonzero. The GPDs are evaluated using the light-front wavefunctions of a quark-diquark model for nucleon where the wavefunctions are constructed by the soft-wall AdS/QCD correspondence. We also express the GPDs in the boost-invariant longitudinal position space.Comment: 13 pages, 10 figures; to appear in Eur. Phys. J. C. arXiv admin note: text overlap with arXiv:1509.0059

Finnish Diabetes Risk Score Is Associated with Impaired Insulin Secretion and Insulin Sensitivity, Drug-Treated Hypertension and Cardiovascular Disease: A Follow-Up Study of the METSIM Cohort

<div><p>We investigated the association of the Finnish Diabetes Risk Score (FINDRISC) with insulin secretion, insulin sensitivity, and risk of type 2 diabetes, drug-treated hypertension, cardiovascular (CVD) events and total mortality in a follow-up study of the <u>Met</u>abolic <u>S</u>yndrome <u>i</u>n <u>M</u>en (METSIM) cohort. The METSIM study includes 10,197 Finnish men, aged 45–73 years, and examined in 2005–2010. Of 8,749 non-diabetic participants of the METSIM study 693 developed incident type 2 diabetes, 225 started antihypertensive medication, 351 had a CVD event, and 392 died during a 8.2-year follow-up. The FINDRISC was significantly associated with decreases in insulin secretion and insulin sensitivity (<i>P</i><0.0001), and with a 4.14-fold increased risk of incident type 2 diabetes, 2.43-fold increased risk of drug-treated hypertension, 1.61-fold increased risk of CVD, and 1.55-increased risk of total mortality (the FINDRISC ≥12 vs. < 12 points). In conclusion, the FINDRISC predicts impairment in insulin secretion and insulin sensitivity, the conversion to type 2 diabetes, drug-treated hypertension, CVD events and total mortality.</p></div

Fasting proinsulin levels across the quintiles of Matsuda ISI and Disposition index in the METSIM cross-sectional and at follow-up studies.

<p>Mean values of fasting proinsulin levels (pmol/l) at baseline and their 95% confidence intervals are shown. Overall P values based on ANOVA across the quintiles of the Matsuda ISI and the Disposition index (both baseline and follow-up) were significant, P<0.001 (Quintiles of the Matsuda ISI: 1—most sensitive 5—least sensitive; Quintiles of the Disposition index: 1—lowest value, 5—highest value).</p

Association of the Finnish Diabetes Risk Score (FINDRISC) with metabolic and clinical traits in 5,401 participants without diabetes or with newly diagnosed type 2 diabetes at the METSIM follow-up visit (linear regression analysis).

<p>Association of the Finnish Diabetes Risk Score (FINDRISC) with metabolic and clinical traits in 5,401 participants without diabetes or with newly diagnosed type 2 diabetes at the METSIM follow-up visit (linear regression analysis).</p

Clinical and metabolic characteristics of participants at the METSIM baseline study in the categories of Finnish Diabetes Risk Score (FINDRISC).

<p>Clinical and metabolic characteristics of participants at the METSIM baseline study in the categories of Finnish Diabetes Risk Score (FINDRISC).</p

Percentage decreases in insulin sensitivity (Matsuda ISI, open circles) and insulin secretion (Disposition index, filled circles, dashed lines) across the Finnish Diabetes Risk Score (FINDRISC) categories compared to the reference category (< 7 points).

<p><b>(A)</b> in the non-diabetic participants of the METSIM baseline study, <b>(B)</b> in the participants of the METSIM 4.6-year follow-up study (participants without diabetes or with newly-diagnosed diabetes at the follow-up examination) <b>(C)</b> in the subcategories of the eight components of the FINDRISC at baseline (reference categories in C for each component respectively are as follows: age<55 years, BMI<25 kg/m², waist<94 cm, physical activity at least 30 min ≥2 times per week, vegetable intake every day, no antihypertensive medication, no history of hyperglycemia, no family history of diabetes). Data are means ± SD.</p

Proinsulin levels across the categories of fasting and 2 hour glucose in the METSIM cross-sectional study.

<p>Mean values of proinsulin levels (pmol/l) and their 95% confidence intervals are shown. Overall P values based on ANOVA across the categories of fasting and 2 hour glucose were significant (P<0.001) for all traits. All mean values were significantly (P<0.001) different from mean values of the reference group (FPG ≤5 mM and 2hr glucose ≤5 mM) except for those marked with ‘x’.</p

Effect of simvastatin on insulin secretion mediated by ATP dependent potassium channels, L-type voltage-gated calcium channels, acetylcholine, and phorbol myristate acetate in MIN6 β-cells.

<p>The effect of simvastatin (Simva, 14.3 μM) on insulin secretion stimulated by tolbutamide (Tol, 100 μM) and potassium chloride (KCl, 40 mM) at 5.5 mM (<b>A</b>) and 16.7 mM glucose concentrations (<b>B</b>); the effect of simvastatin and nifedipine (Nif, 5 μM) on insulin secretion at 5.5 mM (<b>C</b>) and 16.7 mM (<b>D</b>) glucose concentrations; the effect of simvastatin on insulin secretion stimulated by acetylcholine (Ach, 10 μM) at 5.5 mM glucose concentration (<b>E</b>); and the effect of simvastatin on insulin secretion stimulated by phorbol myristate acetate (PMA, 0.5 μM) at 5.5 mM glucose concentration (<b>F</b>); and the effect of simvastatin (14.3 μM) on the PKC activity in MIN6 β-cells at 5.5 and 16.7 mM glucose concentration (<b>G</b>). Insulin secretion was normalized with protein concentration, data are mean ± SEM relative to control (100%). p values were calculated with the Mann-Whitney test, *p<0.05, **p<0.01 compared to control. The number of replicates was 6 for A and E, 8 for B, C, and D, 4 for F, and 2–4 for G.</p

Different pathways of insulin secretion, links between them and effects of simvastatin on these pathways.

<p>Simvastatin (Simva) decreases insulin secretion mediated by ATP-sensitive potassium (K_ATP) channels (A), membrane depolarization and voltage-gated calcium channels (B), and acetylcholine and GPR40 receptors (C and D). These effects may be attributable to simvastatin´s actions on K_ATP channels, calcium channels, or Ca²⁺ release from endoplasmic reticulum <i>via</i> inositol 3-phophate (IP3) and ryanodine receptors (RYR). Activation of GLP-1R (E) and GPR119 (F) pathway restores simvastatin-decreased insulin secretion. DAG—diacylglycerol, EPAC2—exchange protein activated by cAMP 2, ER—endoplasmic reticulum, Inos(1,4,5)P₃ –inositol 1,4,5-triphosphate, PKA—protein kinase A, PLCβ–phospholipase C beta, PtdInos(4,5)P_2—phosphatidylinositol 4,5-bisphosphate.</p

Tissue-specific insulin resistance indices and fasting plasma insulin as predictors of incident type 2 diabetes in the 5.9-years METSIM prospective study, Kuopio, Finland.

<p>Abbreviations: CI, confidence interval; HR, hazard ratio; IR, insulin resistance.</p><p>HRs and their 95% CI were obtained from Cox regression analyses. HRs were calculated using standardized predictors (unit = one standard deviation). Individuals with type 1 diabetes (N = 25), type 2 diabetes (N = 763) or newly diagnosed type 2 diabetes at baseline (N = 649) were excluded. A total of 558 individuals were diagnosed with incident type 2 diabetes during the 5.9 year follow-up, 8,191 participants remained non-diabetic. Bold font indicates statistical significance <i>P<</i>0.0125.</p><p><i>P</i>, unadjusted.</p><p><i>P</i>^a, adjusted for age, BMI, smoking, physical activity, alcohol consumption and family history of type 2 diabetes.</p><p><i>P^b</i>, adjusted for age, BMI, smoking, physical activity, alcohol consumption, family history of type 2 diabetes and disposition index at baseline.</p><p><i>P</i>^c, adjusted for age, BMI, smoking, physical activity, alcohol consumption, family history of type 2 diabetes and glucose AUC at baseline.</p><p><i>P</i>^d adjusted for age, BMI, smoking, physical activity, alcohol consumption, family history of type 2 diabetes, disposition index and glucose AUC at baseline.</p><p>*Matsuda IR was calculated as: 10/Matsuda ISI.</p><p>Disposition index was calculated as: Matsuda ISI×InsAUC_0–30/GluAUC_0–30.</p><p>Tissue-specific insulin resistance indices and fasting plasma insulin as predictors of incident type 2 diabetes in the 5.9-years METSIM prospective study, Kuopio, Finland.</p