Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans

Objective: To study the association of vaspin with glucose metabolism. Design: Cross-sectional and intervention study. Subjects and methods: The association of serum vaspin with metabolic and anthropometric characteristics was investigated in 108 volunteers. Euglycemic–hyperinsulinemic clamps (EHC) were performed in 83 of the participants. Changes of circulating vaspin levels were additionally studied in a crossover study using 300 min EHC with lipid versus saline infusion (n=10). Results: Neither glucose tolerance status nor insulin sensitivity, both as measured using EHCs and using homeostasis model assessment for insulin resistance (HOMA-IR), was significantly associated with serum vaspin in the cross-sectional study. Furthermore, there was no effect of short-term lipid-induced insulin resistance due to a 300 min intravenous lipid challenge on circulating vaspin. However, circulating vaspin levels were significantly elevated in women using oral contraceptives (OC), both compared to women without OC intake (1.17±0.26 vs 0.52±0.09 ng/ml, P=0.02) and males (1.17±0.26 vs 0.29±0.04 ng/ml, P=0.01). After exclusion of OC using females and stratification according to body mass index (BMI), a significant sexual dimorphism in subjects with a BMI <25 kg/m2 was observed (males 0.21±0.04 ng/ml versus females 0.70±0.16 ng/ml, P=0.009). Conclusion: Our results support the existence of a sexual dimorphism regarding circulating vaspin. The lack of an association of serum vaspin with HOMA-IR and M value indicates, however, no major role for vaspin concerning insulin sensitivity in nondiabetic humans

Effects of long-term soluble vs. insoluble dietary fiber intake on high-fat diet-induced obesity in C57BL/6J mice

Although most of the proposed beneficial effects of fiber consumption have been attributed to viscous and gel-forming properties of soluble fiber, it is mainly insoluble cereal fiber and whole grains that are strongly associated with reduced diabetes risk in prospective cohort studies, indicating that other unknown mechanisms are likely to be involved. We performed a long-term study investigating potential protective effects of adding soluble guar fiber (10% w/w) vs. insoluble cereal fiber (10% w/w) to an isoenergetic and macronutrient matched high-fat diet in obesity-prone C57BL/6J mice. After 45 weeks, mice fed soluble vs. insoluble fiber showed both significantly increased body weight (41.8±3.0 vs. 33.6±1.5 g, P=.03) and elevated markers of insulin resistance. In mice fed soluble fiber, energy loss via the feces was significantly lower and colonic fermentation with production of short chain fatty acids (SCFA) was markedly increased. Gene expression analysis in white adipose tissue showed significantly increased levels of the fatty acid target G-protein coupled receptor-40 in soluble fiber-fed mice. Liver gene expression in the insoluble fiber group showed a pattern consistent with increased fatty acid oxidation. The present results show that soluble vs insoluble dietary fiber added to a high-fat, Western-style diet differently affected body weight and estimates of insulin sensitivity in obesity-prone mice. Soluble fiber intake with increased SCFA production significantly contributed to digested energy, thereby potentially outweighing the well known short-term beneficial effects of soluble fiber consumption

Entwicklung und Anwendung einer HPLC gestützten quantitativen RNA-Analyse von drei Isoformen der TGF-β\beta Familie in humanem Knochen

TGF-$\beta$ ist ein multifunktionaler Wachstumsfaktor, der auch für den Stoffwechsel des Knochens entscheidende Funktionen besitzt. Mit Hilfe der RT-PCR in Kombination mit der Hochdruck-Flüssigkeitschromatographie wurde ein Verfahren entwickelt, mit dem RNA aus kleinsten Gewebsproben humaner Knochen äußerst sensitiv meßbar wurden. Mit den Ergebnissen eines Studienkollektivs aus einer Chirurgischen Klinik, wurden mit der Quantifizierung der RNA-Kopien mögliche Einflußgrößen auf die Expression der Gene des TGF-$\beta$1 bis 3 analysiert. Im Vergleich der TGF-$\beta$ Isoformen muß aufgrund der gefundenen Expressionsmuster von einer differentiellen Steuerung der Transkriptionsrate ausgegangen werden. Das Probandenalter, der Vitamin D Haushalt, die Mobilität, der Hormonhaushalt und die Konzentration des zugehörigen Proteins scheinen die RNA-Expression eindeutig zu modulieren

Annual change in insulin sensitivity

The incidence of both type 2 diabetes and cardiac events is reported to be higher during winter, indicating a putative annual periodic change in insulin sensitivity (IS). Annual differences in IS quantified as HOMA-%S and Matsuda-Sensitivity Index - were analyzed using a cosine wave-fitting algorithm in a cross-sectional study group including 2 385 participants. Additionally, semiannual differences in IS were compared. We found periodicity for HOMA-%S and Matsuda-Sensitivity Index (p = 0.02 or 0.006), which was strengthened after restriction to participants without diabetes ( p = 0.009 or 0.004). The rhythm amplitude of 0.08 indicated moderate changes in IS throughout the year. IS was significantly higher when participants were enrolled during the second vs. the first half of the year (HOMA-%S 112.0 +/- 3.0 % vs. 97.4 +/- 2.4 %, p < 0.001). The impact of the half-year on IS, which remained significant after adjustment for confounders, was again moderate and explained only 0.5% of the variation. IS showed a significant moderate annual periodicity, which may affect the interpretation of studies reporting small changes in IS

Deficiency of glucose-dependent insulinotropic polypeptide receptor prevents ovariectomy-induced obesity in mice

Menopause and premature gonadal steroid deficiency are associated with increases in fat mass and body weight. Ovariectomized (OVX) mice also show reduced locomotor activity. Glucose-dependent-insulinotropic-polypeptide (GIP) is known to play an important role both in fat metabolism and locomotor activity. Therefore, we hypothesized that the effects of estrogen on the regulation of body weight, fat mass, and spontaneous physical activity could be mediated in part by GIP signaling. To test this hypothesis, C57BL/6 mice and GIP-receptor knockout mice (Gipr−/−) were exposed to OVX or sham operation (n = 10 per group). The effects on body composition, markers of insulin resistance, energy expenditure, locomotor activity, and expression of hypothalamic anorexigenic and orexigenic factors were investigated over 26 wk in all four groups of mice. OVX wild-type mice developed obesity, increased fat mass, and elevated markers of insulin resistance as expected. This was completely prevented in OVX Gipr−/− animals, even though their energy expenditure and spontaneous locomotor activity levels did not significantly differ from those of OVX wild-type mice. Cumulative food intake in OVX Gipr−/− animals was significantly reduced and associated with significantly lower hypothalamic mRNA expression of the orexigenic neuropeptide Y (NPY) but not of cocaine-amphetamine-related transcript (CART), melanocortin receptors (MCR-3 and MCR-4), or thyrotropin-releasing hormone (TRH). GIP receptors thus interact with estrogens in the hypothalamic regulation of food intake in mice, and their blockade may carry promising potential for the prevention of obesity in gonadal steroid deficiency

Androgen receptor CAG repeat length polymorphism modifies the impact of testosterone on insulin sensitivity in men

Objective: Low circulating testosterone concentrations have been associated with insulin resistance (IR). Androgen action is mediated by the androgen receptor (AR) whose activity is modulated by a polymorphic CAG repeat sequence within exon 1. An interaction between testosterone and CAG repeat length (CAG length) with respect to IR has been described in women. Objective: We investigated such a putative interaction between testosterone and the CAG length with respect to IR in men with normal glucose tolerance. Design: Cross-sectional study. Methods: In 113 non-diabetic men calculated free testosterone, the CAG length, and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with IR, as indicated by homeostasis model assessment (HOMA %S). Results: In a multivariate regression analysis adjusted for age and body mass index, free testosterone, CAG length, and a multiplicative interaction term were significantly associated with IR (P=0.001, P=0.001, P=0.01 respectively). The model explained 36.6% of the variation of IR and predicted that in carriers with a CAG length of 23, changes in testosterone would only minimally affect IR. For CAG lengths longer than 23, however, an increase in testosterone would improve IR, namely the longer the CAG length, the greater the effect. In contrast, in the case of CAG lengths shorter than 23, the effect of increasing testosterone would be the opposite. Conclusions: In men, testosterone and the AR CAG repeat length polymorphism interacted with respect to IR. The interpretation of the association between testosterone and IR seems to require consideration of the AR CAG repeat polymorphism

Hepatic insulin clearance is closely related to metabolic syndrome components

OBJECTIVE Insulin clearance is decreased in type 2 diabetes mellitus (T2DM) for unknown reasons. Subjects with metabolic syndrome are hyperinsulinemic and have an increased risk of T2DM. We aimed to investigate the relationship between hepatic insulin clearance (HIC) and different components of metabolic syndrome and tested the hypothesis that HIC may predict the risk of metabolic syndrome. RESEARCH DESIGN AND METHODS Individuals without diabetes from the Metabolic Syndrome Berlin Brandenburg (MeSyBePo) study (800 subjects with the baseline examination and 189 subjects from the MeSyBePo recall study) underwent an oral glucose tolerance test (OGTT) with assessment of insulin secretion (insulin secretion rate [ISR]) and insulin sensitivity. Two indices of HIC were calculated. RESULTS Both HIC indices showed lower values in subjects with metabolic syndrome (P < 0.001) at baseline. HIC indices correlate inversely with waist circumference, diastolic blood pressure, fasting glucose, triglycerides, and OGTT-derived insulin secretion index. During a mean follow-up of 5.1 ± 0.9 years, 47 individuals developed metabolic syndrome and 33 subjects progressed to impaired glucose metabolism. Both indices of HIC showed a trend of an association with increased risk of metabolic syndrome (HICC-peptide odds ratio 1.13 [95% CI 0.97–1.31], P = 0.12, and HICISR 1.38 [0.88–2.17], P = 0.16) and impaired glucose metabolism (HICC-peptide 1.12 [0.92–1.36], P = 0.26, and HICISR 1.31 [0.74–2.33] P = 0.36), although point estimates reached no statistical significance. CONCLUSIONS HIC was associated with different components of metabolic syndrome and markers of insulin secretion and insulin sensitivity. Decreased HIC may represent a novel pathophysiological mechanism of the metabolic syndrome, which may be used additionally for early identification of high-risk subjects