natriuretic-peptide--brain and Hyperinsulinism

Gut hormones affect cardiac function and contractility. In this study, we examined whether insulin affects the cardiac atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) gene expression and release of proANP-derived peptides in pigs. Anaesthetized pigs were included in an experimental study comparing the effect of hyperinsulinemia in 15 pigs submitted to two different protocols versus 11 control pigs receiving saline infusion. Phosphorylation of Akt on Thr308 was determined by western blotting with a pAkt-Thr308 antibody. The mRNA contents of ANP and BNP were determined with real-time PCR; plasma and cardiac tissue proANP was measured with an immunoluminometric assay targeted against the mid-region of the propeptide and a processing-independent assay. Insulin stimulation increased phosphorylation of Akt Thr308 in both left atrium and left ventricle of porcine hearts (p < 0.005). No change was observed in ANP and BNP mRNA contents in the right or left atrium. BNP mRNA contents in the left ventricle, however, decreased 3-fold (p = 0.02) compared to control animals, whereas the BNP mRNA content in the right ventricle as well as ANP mRNA content in the right and left ventricle did not change following hyperinsulinemia. Moreover, the peptide contents did not change in the four cardiac chambers. Finally, proANP concentrations in plasma did not change during the insulin infusion compared to the control animals. These results suggest that insulin does not have direct effect on atrial natriuretic peptide expression but may have a role in the left ventricle.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Female; Gene Expression Regulation; Glucose Clamp Technique; Heart Atria; Heart Ventricles; Hyperinsulinism; Infusions, Intravenous; Insulin; Natriuretic Peptide, Brain; Phosphorylation; Proto-Oncogene Proteins c-akt; RNA, Messenger; Swine

Our primary aim was to investigate whether N-terminal pro-brain natriuretic peptide (NT-proBNP) increases in adolescent with polycystic ovary syndrome (PCOS) compared with healthy controls and secondary aim was to determine whether metabolic and hormonal differences exist between groups.. In this cross-sectional study, 25 adolescent patients with PCOS and 25 normal ovulatory control not suffering from PCOS were involved in the study. Fasting serum NT-proBNP, C-reactive protein (CRP), homocystein, insulin levels and biochemical and hormonal parameters were measured.. Serum NT-proBNP was not significantly different in PCOS subjects (0.62 ± 0.80 vs 1.12 ± 1.51 ng/mL, p = 0.154). The mean serum fasting insulin levels (22.64 ± 10.51 vs 13.32 ± 3.97 mIU/mL, p = 0.001) and Homeostasis Model Assessment Insulin-Resistance Index (HOMA-IR) levels (5.16 ± 1.81 vs 2.97 ± 0.89, p = 0.001) were significantly high in the study group. The median serum CRP levels were not significantly different between groups (1 [1-12] vs 1 [1-19] g/dL, p = 0.286).. The present study demonstrated that the levels of BNP, CRP and homocystein were not different in PCOS subjects. Serum insulin levels and HOMA-IR were significantly higher in PCOS subjects. Possible serum markers for PCOS-related metabolic abnormalities and cardiovascular events, may not present in the adolescent years.

Topics: Acne Vulgaris; Adolescent; Adolescent Development; Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Cross-Sectional Studies; Early Diagnosis; Female; Hirsutism; Humans; Hyperinsulinism; Insulin Resistance; Natriuretic Peptide, Brain; Oligomenorrhea; Ovary; Peptide Fragments; Polycystic Ovary Syndrome; Turkey; Ultrasonography; Young Adult

B-type natriuretic peptide (BNP), a member of the natriuretic peptide family, is a cardiac-derived secretory hormone with natriuretic, diuretic, and vasorelaxant activities. Intraabdominal fat accumulation is associated with atherosclerotic cardiovascular diseases and cardiac dysfunction. Circulating BNP levels are relatively low (within the normal limits) in obesity and the metabolic syndrome. However, the relationship between plasma BNP levels and visceral fat accumulation in general population has not been reported. The present study analyzed the relationships between plasma BNP levels and various clinical variables, including insulin, visceral and subcutaneous fat area (VFA and SFA, respectively), in normal Japanese men.. The study (Victor-J study) subjects were consecutive 500 Japanese male workers, who underwent a health checkup and were measured VFA and SFA by computed tomography.. Age-adjusted simple linear regression analysis showed that log-BNP correlated positively with HDL-cholesterol, and negatively with VFA, log-immunoreactive insulin (IRI), log-triglyceride, and LDL-cholesterol, but not body mass index or SFA. Stepwise multiple regression analysis identified log-IRI and HDL-cholesterol as significant determinants of log-BNP. Subjects with IRI ≥5.5 μIU/mL had lower plasma BNP levels than those with IRI < 5.5 μIU/mL, irrespective of obesity (body mass index, cutoff value 25 kg/m2), visceral fat accumulation (VFA, cutoff value 100 cm2) and subcutaneous fat accumulation (SFA, cutoff value 128 cm2).. Our study showed that hyperinsulinemia correlated with low levels of plasma BNP in general men, irrespective of fat distribution.. UMIN 000004318.

Topics: Adiposity; Adult; Aged; Analysis of Variance; Asian People; Biomarkers; Cross-Sectional Studies; Down-Regulation; Humans; Hyperinsulinism; Insulin; Intra-Abdominal Fat; Japan; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Subcutaneous Fat; Tomography, X-Ray Computed; Up-Regulation

The natriuretic peptides play an important role in salt homeostasis and blood pressure regulation. It has been suggested that obesity promotes a relative natriuretic peptide deficiency, but this has been a variable finding in prior studies and the cause is unknown.. The aim of this study was to examine the association between obesity and natriuretic peptide levels and evaluate the role of hyperinsulinemia and testosterone as mediators of this interaction.. We studied 7770 individuals from the Framingham Heart Study (n = 3833, 54% women) and the Malmö Diet and Cancer study (n = 3918, 60% women). We examined the relation of plasma N-terminal pro-B-type natriuretic peptide levels (N-BNP) with obesity, insulin resistance, and various metabolic subtypes.. Obesity was associated with 6-20% lower levels of N-BNP (P < 0.001 in Framingham, P = 0.001 in Malmö), whereas insulin resistance was associated with 10-30% lower levels of N-BNP (P < 0.001 in both cohorts). Individuals with obesity who were insulin sensitive had only modest reductions in N-BNP compared with nonobese, insulin-sensitive individuals. On the other hand, individuals who were nonobese but insulin resistant had 26% lower N-BNP in Framingham (P < 0.001) and 10% lower N-BNP in Malmö (P < 0.001), compared with nonobese and insulin-sensitive individuals. Adjustment for serum-free testosterone did not alter these associations.. In both nonobese and obese individuals, insulin resistance is associated with lower natriuretic peptide levels. The relative natriuretic peptide deficiency seen in obesity could be partly attributable to insulin resistance, and could be one mechanism by which insulin resistance promotes hypertension.

Topics: Adult; Androgens; Body Mass Index; Cohort Studies; Diet; Female; Humans; Hyperinsulinism; Insulin Resistance; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Predictive Value of Tests; Testosterone

We wanted to investigate the relationship of N-terminal pro brain natriuretic peptide (Nt-proBNP) to metabolic and hemodynamic cardiovascular (CV) risk factors in the general population. From a population-based sample of 2656 people 41, 51, 61, or 71 years of age, we selected 2070 patients without previous stroke or myocardial infarction who did not receive any CV, antidiabetic, or lipid-lowering treatment in 1993 to 1994. Traditional CV risk factors, 24-hour blood pressures, left ventricular (LV) mass, and ejection fraction by echocardiography, pulse wave velocity, urine albumin/creatinine ratio (UACR), and serum Nt-proBNP were measured in 1993 to 1994. The metabolic syndrome was defined in accordance with the definition of the European Group for the Study of Insulin Resistance (EGIR). Higher log(Nt-proBNP) was in multiple regression analysis related to female gender (beta=-0.37), older age (beta=0.32), higher clinic pulse pressure (beta=0.20), lower serum total cholesterol (beta=-0.15), lower LVEF (beta=-0.08, all P<0.001), lower log(serum insulin) (beta=-0.07), lower log(plasma glucose) (beta=-0.06, both P<0.01, lower log(serum triglyceride) (beta=-0.06), lower body mass index (beta=-0.05); lower heart rate (beta=-0.05), higher logUACR (beta=0.04, all P<0.05) and higher log(LV mass index) (beta=0.04, P=0.07), adjusted R2=0.35, P<0.001). The metabolic syndrome was associated with lower Nt-proBNP (35 pg/mL versus 48 pg/mL; P<0.001) and shifted the positive relationship between pulse pressure and Nt-proBNP to the right (ie, higher blood pressure for a given level of Nt-proBNP). The metabolic syndrome was associated with lower Nt-proBNP levels and shifted the positive relationship between Nt-proBNP and pulse pressure to the right, creating a possible link between the metabolic syndrome and hypertension.

Topics: Adult; Aging; Blood Pressure; Cardiovascular Diseases; Dyslipidemias; Echocardiography; Female; Humans; Hyperinsulinism; Hypertension; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Risk Factors; Sex Factors; Stroke Volume