Secretion of Insulin During Aging

Abstract

ecognition of and response to environmental challenge are expressed in part by the availability and efficacy of circulating hormones for R the modulation of intermediary metabolism in target cells. One example of such adaptive capability that changes during aging is the impact of dietary glucose on its insulin-sensitive metabolism by liver and peripheral tissues. This paper provides a critical review of published research that addresses the pivotal role of insulin secretion in that adaptive sequence during aging.According to most, but not all, published reports, the regulation of insulin secretion by glucose changes during aging. However, interpretation of these data is complicated by numerous factors, most prominent of which include 1) the extent to which it is possible to evaluate insulin secretion in vivo by measurement of hormone levels in peripheral blood; 2) the distribution of functionally heterogeneous populations of pancreatic islets of Langerhans; 3) distinctions between growth, obesity, and aging; and 4) the frequent failure to acknowledge relevant, previously published literature. The present paper will examine these data both in the context of such complications and from the perspective of the pursuit of further insight into the fundamental biological processes of aging that are expressed in the absence of disease and inappropriate lifestyle. ALTERED RESPONSIVENESS TO GLUCOSE IN VIVOWhen the pancreas recognizes and responds to an increased level of blood glucose, insulin is secreted into the portal vein and through it is transported immediately to the liver. Within the liver insulin exerts certain of its hormonal actions and also is metabolized. The proportion of insulin molecules that escapes its hepatic metabolism is distributed throughout the peripheral circu-From the Institute of Gerontology, The University of Michigan, Ann Arbor, Michigan. Address correspondence and reprint requests to Richard C. Adelman, PhD, Institute of Gerontology, The University of Michigan, 300 N. Ingalls, Ann Arbor, MI 48109-2007.lation and tissues. Therefore, assessment of insulin secretion by the pancreas into the circulation can be approximated most accurately in portal vein blood.The concentration of insulin in portal vein blood is the net result of its secretion into the blood by the pancreas and its extraction from the blood by the liver at early points during the secretory response, although recirculation of secreted insulin complicates matters increasingly with the passage of time. However, the concentration of insulin in peripheral blood at any given time represents the far more complex net result of its pancreatic secretion, hepatic clearance, uptake and clearance through peripheral tissues, recirculation, and disposition within the blood. Therefore, consideration of peripheral blood insulin levels during aging in the context of the regulation of insulin secretion is excluded from this review, although previous work by Chen et al,' for example, is particularly relevant in this regard.The pattern of insulin respo...

Effect of inhibition of α-glucosidase on age-related glucose intolerance and pancreatic atrophy in rats

“…Therefore, it is likely that the mesenteric fat depot increased and thereby insulin resistance ensued in the A12-28W group. Although many studies have examined the effect of aging on insulin secretory function, there is a great deal of variability in the outcome of these studies [39]. In our study, insulin secretory function evaluated by the insulinogenic index at IVGTT was unaltered with increasing age in the control group, and acarbose treatment showed no influence on the insulinogenic index (data not shown).…”

Decrease in Glucose-Stimulated Insulin Secretion With Aging Is Independent of Insulin Action

“…In light of a functional decrease in insulin secretion with aging, it is rather interesting that islet number, islet size, and secretory granules are actually increased in old SD rats compared with young animals (29,30). Despite the increased size of the islets, the release of insulin in response to glucose is decreased in old age in vitro (31)(32)(33)(34).…”

Aging and insulin secretion

“…Many studies have examined the effects of aging on pancreatic ␤-cell function in humans, although there is a great deal of variability in the outcomes of these studies (1). This variability may be due to multiple factors, including the small magnitude of the age effect, the use of different measures of insulin secretion, and confounding factors associated with aging such as obesity, decreased physical activity, and concomitant insulin resistance.…”