The effects of NN414, a SUR1/Kir6.2 selective potassium channel opener, in healthy male subjects.

The aim of the present study was to investigate the effect of a single dose of NN414 (a selective SUR1/Kir6.2 potassium channel opener). Sixty-four healthy male subjects were enrolled at 8 dose levels (0.

Coupling of oral human or porcine insulin to the B subunit of cholera toxin (CTB) overcomes critical antigenic differences for prevention of type I diabetes.

Our earlier investigations have demonstrated a critical difference in the efficacy of orally administered porcine compared to human or mouse insulin (no effect) in preventing type I diabetes in two distinct experimental models. Based on these findings one has to assume that certain insulins might not be suitable for the induction of oral 'tolerance'/bystander suppression, which might be one cause for recent failures in human oral antigen trials. Here we demonstrate that coupling to the non-toxic subunit of cholera toxin (CTB) can abolish these differences in efficacy between human and porcine insulin.

The cholera toxin B subunit is a mucosal adjuvant for oral tolerance induction in type 1 diabetes.

When conjugated to various proteins, the nontoxic B-chain of cholera toxin (CTB) significantly increases the ability of these proteins to induce immunological tolerance after oral administration. Here, we investigated if a nonconjugated form of CTB enhances the induction of immune tolerance after oral insulin administration. Induction of immunological tolerance was studied after oral administration of insulin preparations in three mouse models; an insulin/ovalbumin coimmunization model, a model of virus-induced diabetes in transgenic RIP-LCMV-NP mice and in nonobese diabetic (NOD) mice serving as a model of spontaneous diabetes.

A new model for analyzing immunomodulation of T cell responses induced by oral administration of islet cell antigens.

Based on the coimmunization of BALB/c mice with insulin and ovalbumin, we here describe a feasible efficacy model for analyzing the tolerogenic effect of the oral administration of sequestered antigens-for example, islet-specific proteins such as insulin and GAD65.

Diagnostic role of antibodies to glutamic acid decarboxylase in latent autoimmune diabetes mellitus in adults.

Objective: To investigate the diagnostic role of antibodies to glutamic acid decarboxylase (GAD65-Ab) in latent autoimmune diabetes of adults (LADA) and the frequency of GAD-Ab in Chinese patients initially diagnosed as non-insulin-dependent diabetes mellitus (NIDDM).

Methods: Forty-five control subjects and 195 consecutive inpatients initially classified as NIDDM with > or = 35 years of age at onset and nonketotic history for > 6 months after diagnosis, were recruited. In vitro transcripted and translated recombinant human 35S-GAD65 was used in radioligand assay of GAD-Ab.