Extrapancreatic insulin-producing cells in multiple organs in diabetes

• DOI: 10.1073/pnas.0308690100
• Publication Date: 2004-02-25T04:03:03Z
• Authors: Hideto Kojima; Mineko Fujimiya; Kazuhiro Matsumura; Tamio Nakahara; Manami Hara; Lawrence Chan
• Keywords: Proinsulin

Insulin-producing cells normally occur only in the pancreas and thymus. Surprisingly, we found widespread insulin mRNA protein expression different diabetic mouse rat models, including streptozotocin-treated mice rats, ob / mice, fed high-fat diets. We detected proinsulin- insulin-positive liver, adipose tissue, spleen, bone marrow, thymus; many also produced glucagon, somatostatin, pancreatic polypeptide. By situ nucleic acid hybridization, diabetic, but not nondiabetic, liver exhibited transcript-positive cells, indicating that was synthesized by these cells. In transgenic express GFP driven promoter, streptozotocin-induced diabetes led to appearance of GFP-positive marrow; fluorescent signals showed complete concordance with presence immunoreactive proinsulin. Hyperglycemia glucose injections nondiabetic within 3 days. Bone marrow transplantation experiments most extrapancreatic proinsulin-producing originated from marrow. Immunoreactive were extrapancreatic, extrathymic production occurs more than one species. These observations have implications for regulation gene expression, modulation self-tolerance strategies generation insulin-producing treatment diabetes.