Brent Wright, Brigham Young University
Life Sciences
Diabetes is one of the leading causes of death among Americans and is a major health concern worldwide. Nearly one in four Americans aged 65 or older are diabetic. Type 1 and Type 2 diabetes both result in reduced functional β-cell mass, which regulates the storage and secretion of insulin. Increased functional β-cell mass could essentially cure diabetes. We have shown that Nkx6.1 overexpression induces proliferation of 2-month-old primary rat β-cells but fails to induce replication of 8-month-old primary β-cells, as measured by 3H- thymidine incorporation is age-dependent. Cell cycle activator and inhibitor mRNA levels were measured in young and aged untreated islets and islets transduced with AdCMV-BGal or AdCMV-Nkx6.1. This data demonstrated a significant increase in mRNA expression of cell cycle inhibitors p21 and p57 of the CIP/KIP family in young islets transduced with Nkx6.1. However, p21 and p57 mRNA showed no significant increase in aged islets. Cdk2 and cyclin E1 mRNA expression showed a similar trend for young and aged islets. The increased expression of Cdk2, a necessary factor for transition from G1 to S phase, could provide possible explanation for increased proliferation in young islets. Fluctuating mRNA levels of key cell cycle components in aged islets, provides a possible explanation for the decreased effectiveness of Nkx6.1 in inducing proliferation in aged islets.