Altered regulation of insulin secretion by glucose is characteristic of individuals with type 2 diabetes mellitus, although the mechanisms that underlie this change remain unclear. We have now generated mice that lack the lambda isoform of PKC in pancreatic beta cells (betaPKClambda(-/-) mice) and show that these animals manifest impaired glucose tolerance and hypoinsulinemia. Furthermore, insulin secretion in response to high concentrations of glucose was impaired, whereas the basal rate of insulin release was increased, in islets isolated from betaPKClambda(-/-) mice. Neither the beta cell mass nor the islet insulin content of betaPKClambda(-/-) mice differed from that of control mice, however. The abundance of mRNAs for Glut2 and HNF3beta was reduced in islets of betaPKClambda(-/-) mice, and the expression of genes regulated by HNF3beta was also affected (that of Sur1 and Kir6.2 genes was reduced, whereas that of hexokinase 1 and hexokinase 2 genes was increased). Normalization of HNF3beta expression by infection of islets from betaPKClambda(-/-) mice with an adenoviral vector significantly reversed the defect in glucose-stimulated insulin secretion. These results indicate that PKClambda plays a prominent role in regulation of glucose-induced insulin secretion by modulating the expression of genes important for beta cell function.

After introducing biological DMARDs, increase of ccfDNA at 8 weeks was associated with improvement of disease activities. Compared with biomarkers reported, ccfDNA is able to predict the early therapeutic effects of biological DMARDs in RA patients.

A relatively small mass of macroencapsulated islet tissue can survive and function well enough to normalize glucose levels for at least 12 weeks. Maintenance of glucose levels in the near-normal range seems to have a beneficial influence on graft success. The finding of fasting hypoglycemia raises important clinical questions about islet dysfunction. Important limitations in the requirements for islet packing density in macroencapsulation have been defined. New approaches for improving islet packing density must be developed to make diffusion-dependent macroencapsulation more practical.

Abstract. Obesity and systemic oxidative stress are closely related. however data concerning the relationships between oxidative stress and body fat mass distribution are sparse. Anthropometric and metabolic profile was evaluated in 148 clinically healthy middle-aged women to assess the correlations between oxidative stress, fat mass distribution, adipokines, and inflammatory markers. Systemic oxidative stress was assessed by urinary creatinine-indexed 8-epi-prostaglandin F-2α (8-epi-PGF 2α ). Body fat mass distribution was examined by dual-energy X-ray absorptiometry (DXA). Lipid profile, adipokines and inflammatory markers including leptin, adiponectin, high sensitive C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α (TNF-α) were determined. We found body mass index (BMI), waist circumference (WC), both central and peripheral DXA-derived regional fat mass (FM) accumulations were positively correlated with 8-epi-PGF 2α . Leptin, hsCRP and PAI-1also positively associated with 8-epi-PGF 2α . after adjustment for BMI and WC, lower-body FM, total FM and PAI-1 retained significant association with 8-epi-PGF 2α . mutliple linear regression analyses indicated lower-body FM and PAI-1 were the two important predicators of 8-epi-PGF 2α . These results suggest that dXa-derived regional Fm indices, especially low extremity adiposity, are more closely associated with systemic oxidative stress than indirect anthropometric indices. Positive associations between 8-epi-PGF 2α and PAI-1, hsCRP, leptin support the notion that oxidative-stress-induced dysregulation of inflammation and adipokines may mediate the obesity-related metabolic derangement.

Aim:We determined the association of lower-body fat mass (LFM) and trunk fat mass (TFM) with cardiometabolic risk factors and adipokines in young, healthy, slim women. Methods: A total of 481 college female students underwent the following: regional body fat distribution as assessed by dual energy X-ray absorptiometry (DXA), a 75g oral glucose tolerance test (OGTT) and fasting blood sampling for measurement of lipids, lipoproteins, apolipoproteins (apo), liver enzymes and adipokines. Results: After adjusting for TFM, LFM was positively associated with HDL cholesterol, adiponectin, pre-heparin lipoprotein lipase and insulin sensitivity, as estimated by the Matsuda index, whereas it was negatively related to triglycerides, apo B, apo B/A1 ratio, small dense LDL, FFA, glucose and insulin at 2h during OGTT, area under the curve of insulin response during OGTT and the white blood cell count. Participants were divided into 9 groups according to tertiles of TFM and LFM. In the middle tertile of TFM, HDL cholesterol and adiponectin increased and triglycerides, apoB/A1 ratio and plasminogen-activator inhibitor-1 decreased from the low to high LFM tertiles. Gammaglutamyltransferase levels in middle and high LFM tertiles were lower than in the lower LFM tertile. Conclusion: For a given level of trunk fat mass, a higher lower-body fat mass is associated with an advantageous profile of not only blood lipoproteins but also serum adipokines, even in healthy, slim women in early adulthood. J Atheroscler Thromb, 2011; 18:365-372.

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The aim of this study was to assess whether the gender-specific pattern of fat mass (FM) distribution is related to gender differences in cardiometabolic risk factors. 207 healthy middle-aged Japanese were included in the study. We measured FM in the total body, trunk, and lower-body with dual-energy X-ray absorptiometry (DXA). The percentage of trunk FM (TFM) and lower-body FM (LFM) is noted as %TFM and %LFM, respectively. Other measurements included glucose and insulin during oral glucose tolerance test (OGTT), leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and systemic oxidative stress marker. Arterial properties were indicated by cardio-ankle vascular index (CAVI) and intima-media thickness (IMT) of the common carotid artery. The results showed that %TFM is higher whereas %LFM is lower in men than in women and men have a more atherogenic cardiometabolic profile. In both genders, %TFM (%LFM) is related to an unfavorable (favorable) cardiometabolic profile. In particular, the relation between %LFM and OGTT-derived insulin sensitivity index is stronger in women than in men. These findings suggested that in relatively healthy adults, android and gynoid pattern of FM distribution contributes to gender differences in cardiometabolic risk factors.