Machi Kanna

Peptidyl-prolyl Cis/Trans Isomerase NIMA-interacting 1 Associates with Insulin Receptor Substrate-1 and Enhances Insulin Actions and Adipogenesis

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a unique enzyme that associates with the pSer/Thr-Pro motif and catalyzes cis-trans isomerization. We identified Pin1 in the immunoprecipitates of overexpressed IRS-1 with myc and FLAG tags in mouse livers and confirmed the association between IRS-1 and Pin1 by not only overexpression experiments but also endogenously in the mouse liver. The analysis using deletion- and point-mutated Pin1 and IRS-1 constructs revealed the WW domain located in the N terminus of Pin1 and Ser-434 in the SAIN (Shc and IRS-1 NPXY binding) domain of IRS-1 to be involved in their association. Subsequently, we investigated the role of Pin1 in IRS-1 mediation of insulin signaling. The overexpression of Pin1 in HepG2 cells markedly enhanced insulin-induced IRS-1 phosphorylation and its downstream events: phosphatidylinositol 3-kinase binding with IRS-1 and Akt phosphorylation. In contrast, the treatment of HepG2 cells with Pin1 siRNA or the Pin1 inhibitor Juglone suppressed these events. In good agreement with these in vitro data, Pin1 knock-out mice exhibited impaired insulin signaling with glucose intolerance, whereas adenoviral gene transfer of Pin1 into the ob/ob mouse liver mostly normalized insulin signaling and restored glucose tolerance. In addition, it was also demonstrated that Pin1 plays a critical role in adipose differentiation, making Pin1 knock-out mice resistant to diet-induced obesity. Importantly, Pin1 expression was shown to be up-regulated in accordance with nutrient conditions such as food intake or a high-fat diet. Taken together, these observations indicate that Pin1 binds to IRS-1 and thereby markedly enhances insulin action, essential for adipogenesis.

Macrophage foam cell formation is augmented in serum from patients with diabetic angiopathy

The differentiation of macrophages into cytokine-secreting foam cells plays a critical role in the development of diabetic angiopathy. J774.1, a murine macrophage cell line, reportedly differentiates into foam cells when incubated with oxidized LDL, ApoE-rich VLDL or WHHLMI (myocardial infarction-prone Watanabe heritable hyperlipidemic) rabbit serum. In this study, serum samples from Type 2 diabetic patients were added to the medium with J774.1 cells and the degree of foam cell induction was quantified by measuring lipid accumulation. These values were calculated relative to the activities of normal and WHHLMI rabbit sera as 0% and 100%, respectively, and termed the MMI (Macrophage Maturation Index). These MMI values reflected intracellular lipids, including cholesteryl ester assayed by GC/MS. Statistical analysis revealed MMI to correlate positively and independently with serum triglycerides, the state of diabetic retinopathy, nephropathy and obesity, but negatively with administration of alpha-glucosidase inhibitors or thiazolidinediones. Taken together, our results suggest that this novel assay may be applicable to the identification of patients at risk for rapidly progressive angiopathic disorders.

Ethanol Production from Hydrothermal Pretreated Empty Fruit Bunches

Separate hydrolysis and fermentation (SHF) is the common process in producing ethanol from lignocellulosic biomass. Nowadays, simultaneous saccharification and fermentation (SSF) process has been seen as potential process for producing ethanol with shortens process time with higher yield of ethanol. Hence, in the current work, the utilization of empty fruit bunches (EFB) in SSF process was studied. In order to improve saccharification reactivity of EFB, hydrothermal pretreatment at 180 and 220 °C was used to pretreat EFB. The findings showed that SSF has the potential in producing ethanol from EFB.