Impaired glucose metabolism has long been associated with aging. Regardless of the cause, experts predict that 41.5% of people 65-74 years of age will experience impaired glucose tolerance of non-insulin dependent diabetes mellitus (NIDDM) in their lifetime. NIDDM and other pathological conditions involving disregulation of glucose metabolism that are more prevalent in the elderly present an enormous financial burden and untold suffering to millions. Despite the effects of numerous investigators studying this problem, there are still many unanswered questions, especially in regard to insulin stimulation and secretion during aging. Recently cytokines, such as interleukin-1beta (IL-1beta), have been shown to affect insulin secretion. We have shown that central injection of IL-1beta causes an inhibition of insulin secretion in spite of significantly elevated plasma glucose levels. This, coupled with the fact that levels of IL-1 changes during aging in humans and rats, lead us to propose that altered levels of IL-1 beta within the brain of old rats compared to young rats may be responsible for a disregulation of insulin secretion. To test this hypothesis, we intend to determine if there are age-dependent changes in IL-1beta levels in the rat brain. Studies will be undertaken in 24 hour fasted young-adult (5 month) and old (29 month) male Fischer 344 (F344) rats to determine the plasma levels of glucose, insulin, glucagon, IL-1beta, and central levels of IL-1beta at various times after an oral glucose load. Next, we will determine if there are age-dependent changes in the inhibition of insulin secretion produced by centrally injected rat recombinant IL-1beta (rrIL-1beta) by measuring the plasma levels of glucose, insulin, glucagon, and IL-1beta after intracerebroventricular (i.c.v.) Infection of IL-1beta. This research will lead to a better understanding of the alternations in glucose metabolism observed during aging and, possibly, to more effective treatments for this problem.
