Decreased Reg I expression underlies age-related impairment of glucose tolerance

• DOI: 10.1016/j.jss.2003.08.069
• Publication Date: 2003-10-15T13:18:13Z
• Authors: E. Kandil; H. Zhang; D. Beckles; Y. Lin; G. Callender; C. Muller; V. Ocasio; M. Zenilman
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences

Abstract Introduction: Diabetes mellitus has been shown to be inversely correlated with pancreatic Reg I gene expression. We hypothesized that with aging, endogenous Reg I expression decreases as glucose tolerance worsens in elderly rats. Methods: The effects of age were investigated by subjecting twelve- and one-month-old female Wistar rats (n = 5 per group) to intraperitoneal glucose tolerance tests (IPGTT, 1 gm/kg D-glucose). We also examined the role of Reg I in young animals by selective blockade of its expression. Monoclonal anti-Reg I antibody (2.5 mg/kg) was chronically infused into the circulation of young animals using subcutaneous osmotic pumps for 7 days; normal mouse IgG was used as a treatment control (n = 5 per group). Pancreatic mRNA and protein levels of Reg I were determined by real-time PCR and Western blot, respectively. Glucose levels were then measured and glucose area under the curve (GAUC) was determined. Results: GAUC was significantly lower in the younger experimental group than in the aged animals (P Conclusion: Decreased Reg I expression in aging rats contributes to their worsening glucose tolerance, suggesting that Reg I gene upregulation might improve glucose tolerance in the elderly.