Combination therapy of systemic and local metformin improves imiquimod-induced psoriasis-like lesions with type 2 diabetes: the role of AMPK/KGF/STAT3 axis.

CONTEXT: Insulin resistance and a disturbed lipid profile are common associations with type 2 diabetes mellitus (T2DM) and different skin diseases, particularly psoriasis (PsO).

OBJECTIVES

We investigated potential therapeutic mechanisms of metformin in a murine animal model of psoriasiform lesions in T2DM.

MATERIALS AND

METHODS

Forty-two rats were randomly divided into control, PsO, and type II DM (T2DM) groups. After confirmation of DM, the type II diabetic rats were allocated into T2DM+ PsO, T2DM+ PsO+ systemic metformin (S. met), T2DM+ PsO+ topical metformin (T. met)), and T2DM+ PsO + combined metformin (C. met). PsO was induced by topical imiquimod.

RESULTS

Systemic administration of the cornerstone antidiabetic drug, metformin, was able to improve insulin resistance and lipid profile. At molecular levels, both topical and systemic metformin significantly increased AMP-activated protein kinase (AMPK), and lowered keratinocyte growth factor (KGF) / "Signal transducer and activator of transcription" (STAT)3 protein levels, and the IL-17RA and IL-17RC gene expression.

CONCLUSION

Although its glucose-controlling effect was not optimum, T.met gel served anti-psoriatic and anti-inflammatory effects.