Age and obesity linked abberations in glucose metabolism and insulin-responsiveness associated with the development of age-related adult onset diabetes are well known, however the etiology of these phenomena is unknown. From existing reports and preliminary investigations the applicant proposes the following: 1) That lactate within normal physiological concentrations is capable of modulating insulin-stimulated glucose metabolism such that a net """"""""glucose-sparing"""""""", with subsequent hyperglycemia, hyper-insulinemia, and eventual insulin-resistance, can occur. 2) That age and/or obesity associated changes in the adipose-tissue metabolism of lactate occur, resulting in chronically elevated lactate levels, resultant """"""""glucose-sparing"""""""" and the sequellae leading to adult onset diabetes. 3) That the dietary induced abberations in glucose metabolism associated with increased sucrose consumption may be mediated through the chronic overproduction of lactate from the fructose component of sucrose and the subsequent effects of elevated lactate levels. The applicant proposes to investigate these phenomena utilizing in vitro studies on fat cells prepared from obese and aging rat models to study age and obesity related changes in net lactate release, lactate effects on glucose intermediary metabolism, insulin dose responses, total glucose utilization, glucose analogue uptake, and insulin binding; in situ studies on the net production and release of lactate under various metabolic conditions; and in vivo probes examining: the relationship among adiposity, age, nutrition, and circulating lactate levels; short and long term effects of elevated lactate levels on glucose tolerance and peripharal uptake of glucose.
| West, D B; Prinz, W A; Francendese, A A et al. (1987) Adipocyte blood flow is decreased in obese Zucker rats. Am J Physiol 253:R228-33 |
