Therapeutic vaccine against IL-1ß improved glucose control in a mouse model of type 2 diabetes.

AIMS: Inflammation is strongly associated with the mechanism of ß-cell failure in type 2 diabetes mellitus (T2DM). Blockade of the key proinflammatory cytokine IL-1ß has been implicated as a promising therapeutic strategy for the prevention and treatment of type 2 diabetes. In this study, we developed an IL-1ß-targeted therapeutic vaccine consisting of an IL-1ß epitope peptide (A1ß) and assessed its efficacy on a diabetic KK-Ay mouse model. MAIN METHODS: KK-Ay mice were immunized with A1ß for three injections at a 2-week interval. The induced antibody titers, body weights and blood glucose levels were monitored every two weeks. Then the intraperitoneal glucose tolerance test and insulin tolerance test were performed. The ß-cell mass, ß-cell apoptosis and proliferation were evaluated by immunofluorescence. IL-1ß gene expression in islets was also measured by quantitative RT-PCR. KEY FINDINGS: A1ß immunization induced robust antibody responses, reduced body weight gain, improved glucose tolerance and insulin sensitivity in KK-Ay mice. Moreover, A1ß restored ß-cell mass, inhibited ß-cell apoptosis, enhanced ß-cell proliferation and downregulated IL-1ß expression. SIGNIFICANCE: The novel IL-1ß-targeted epitope vaccine has the therapeutic potential for T2DM.

Intravenous immunoglobulin improves glucose control and ß-cell function in human IAPP transgenic mice by attenuating islet inflammation and reducing IAPP oligomers.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by ß-cell loss, insulin resistance, islet inflammation and amyloid deposits derived from islet amyloid polypeptide (IAPP). Reducing toxic IAPP oligomers and inhibiting islet inflammation may provide therapeutic benefit in treating T2DM. Intravenous immunoglobulin (IVIg) is an efficient anti-inflammatory and immunomodulatory agent for the treatment of several autoimmune or inflammatory neurological diseases. However, whether IVIg has therapeutic potential on T2DM remains unclear. In present study, we showed that IVIg treatment significantly improved glucose control and insulin sensitivity, and prevented ß-cell apoptosis by lowering toxic IAPP oligomer levels, attenuating islet inflammation and activating autophagy in human IAPP transgenic mouse model. These results suggest that IVIg is a promising therapeutic potential for T2DM treatment.