In conclusion, our data indicate that the histaminergic system plays a vital role in the onset of hyperglycaemia health complications and that the use of the CNS-sparing histamine H3 receptor may be an essential tool in the prevention of nitrergic dysfunction in the myenteric plexus of the distal colon and, therefore, in diabetes-induced GI complications. This evidence concerns the gene HRH3 and diabetes mellitus.