GIP-induced cAMP production is blunted when rat or human pancreatic islets are cultured under conditions of high glucose, and treatment of isolated islets with the proteasomal inhibitors lactacystin or MG-132 prevents glucose-stimulated downregulation of Gipr, and preserves GIP-induced cAMP production, suggesting that hyperglycemia promotes degradation of GIPR by stimulating its ubiquitination [170]. The gene discussed is GIPR; the disease is Hyperglycemia.