Fast-acting insulin aspart in Japanese patients with type 1 diabetes: Faster onset, higher early exposure and greater early glucose-lowering effect relative to insulin aspart.

Introduction: Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with two added excipients (niacinamide and L-arginine) in order to obtain accelerated absorption after subcutaneous dosing. The present study compared the pharmacokinetic/pharmacodynamic characteristics of faster aspart vs IAsp in Japanese patients with type 1 diabetes.

Materials And Methods: In a randomized, double-blind, cross-over design, 43 participants were given faster aspart and IAsp (0.

PKC-θ exists in an oxidized inactive form in naive human T cells.

PKC-θ plays a central role in TCR-induced IL-2 production and T-cell proliferation. The aim of the present study was to analyse how PKC-θ is regulated in human T cells during T-cell activation and differentiation. We show that PKC-θ is found in a high-molecular disulfide-linked complex in naïve T cells, and that PKC-θ most likely is inactive in this form.

Activated human CD4+ T cells express transporters for both cysteine and cystine.

Because naïve T cells are unable to import cystine due to the absence of cystine transporters, it has been suggested that T cell activation is dependent on cysteine generated by antigen presenting cells. The aim of this study was to determine at which phases during T cell activation exogenous cystine/cysteine is required and how T cells meet this requirement. We found that early activation of T cells is independent of exogenous cystine/cysteine, whereas T cell proliferation is strictly dependent of uptake of exogenous cystine/cysteine.

Polymorphisms of the T cell receptor CD3delta and CD3epsilon chains affect anti-CD3 antibody binding and T cell activation.

T cell receptor (TCR) structure and function have been thoroughly studied for decades. Production and analyses of knock-out and knock-in mice with mutations in the CD3 chains have contributed significantly to these studies. The generation of such gene-modified mice relies on the availability of suitable embryonic stem (ES) cell lines.

TCR down-regulation controls T cell homeostasis.

TCR and cytokine receptor signaling play key roles in the complex homeostatic mechanisms that maintain a relative stable number of T cells throughout life. Despite the homeostatic mechanisms, a slow decline in naive T cells is typically observed with age. The CD3gamma di-leucine-based motif controls TCR down-regulation and plays a central role in fine-tuning TCR expression and signaling in T cells.

TCR down-regulation controls virus-specific CD8+ T cell responses.

The CD3gamma di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3gamma di-leucine-based motif in physiological T cell responses. In this study, we show that the expansion in numbers of virus-specific CD8(+) T cells is impaired in mice with a mutated CD3gamma di-leucine-based motif.

Cellular dynamics in the draining lymph nodes during sensitization and elicitation phases of contact hypersensitivity.

Background: The different role of various immunological effector cells in contact hypersensitivity (CHS) is receiving increased attention. During the past decade, the involvement of different cell types in CHS has been investigated by the use of antibody-induced depletion of specific subtypes of immunological cells and by studying knockout mice lacking one or more of these immunological cell populations.

Objectives: To develop a method for studying the collective cellular dynamics of immune cells in the draining lymph nodes during CHS in intact animals.