As a proof of concept, we show that percutaneous delivery of NG from clinically licensed dermal patches placed above subcutaneously implanted microencapsulated hNORM-transgenic human cells provides precise, reversible and dynamic NO-triggered control of the expression of the therapeutic protein GLP-1, and can successfully treat experimental type 2 diabetes and obesity in mice over a prolonged period, without affecting parameters such as heart rate and blood pressure. The gene discussed is GCG; the disease is obesity due to melanocortin 4 receptor deficiency.