Effect of age on glucose-stimulated insulin release by the beta-cell of the rat.

Abstract

A B S T R A C T To assess the effect of age on 18-cell insulin release, collagenase-isolated islets of Langerhans were obtained from rats aged 2-18 mo and incubated with increasing concentrations of glucose. Similar islets were analyzed for insulin content or subjected to morphometric measurements to identify both the number of 13-cells and the volume of 8-granules per islet. In parallel studies, the islet content of intact pancreata was also determined. The results showed thatf1-cell number increased from 2,300 to 5,000 cells as rats aged from 2 to 18 mo and islet insulin content doubled. However, glucose-stimulated insulin release decreased progressively with age, and this was especially striking when considered in terms of the increase in number of,1-cells/islet; e.g., mean (±SEM) insulin secretion (nanounits per minute per ,8-cell) of islets incubated with 450 mg/dl of glucose was 1.3 (±0.2), 1.0 (±0.1), 0.4 (±0.05), and 0.3 (±0.01), respectively for 2-, 6-, 12-, and 18-mo-old rats. Thus, insulin secretion per 13-cell was decreased, despite increased stores of insulin per cell. These findings demonstrate that the aging process leads to a profound defect in glucose-stimulated insulin release from the ,8-cell. Whether this is a global secretory defect, or solely a failure ofthe ,3-cell to respond to glucose, remains to be defined.

Insufficient adaptive capability of pancreatic endocrine function in dexamethasone-treated ageing rats

“…Stimulation of insulin release in isolated islets from aged untreated rats highlights a diminished responsiveness to glucose alone or in combination with other secretagogues, in agreement with previous observations (Reaven et al 1979, Bergamini et al 1991, Inoue et al 1997. This reduced response was particularly remarkable in the islets from the oldest control group.…”

“…Several in vitro studies have indicated an impairment in insulin secretion with advancing age, since isolated islets from older rats do not release insulin as rapidly and efficiently as do islets from younger rats (Reaven et al 1979, Sartin et al 1986, despite partial compensation due to the development of islet hypertrophy and/or hyperplasia (Reaven et al 1979, Coordt et al 1995. On the other hand, studies in intact animals and man have generally shown that circulating insulin levels are either unchanged or even increased after a glucose challenge in senescence (Palmer & Ensinck 1975, De Fronzo 1979.…”

Length of metabolic normalization after rat islet cell transplantation depends on endocrine cell composition of graft and on donor age

“…The vicinity of glucagon-producing alpha cells could improve the survival of beta cells during culture or during the first posttransplantation days, thus leading to engraftment of a larger functional beta-cell mass than when the same number of beta cells is aggregated without alpha cells. The latter implants may -as a consequence -contain a marginally low beta-cell mass, and therefore become functionally inadequate at a later time, when insulin needs have increased as a result of the greater body weight and/or older age of the recipients [10,11,20]. It is also conceivable that the local release of glucagon amplifies the beta cells' secretory response to glucose, thus enhancing their homeostatic control.…”

Evaluation of rat insulin messenger RNA in pancreatic and extrapancreatic tissues

“…Using this method we have quantified insulin mRNA in islets, insulinoma cells adapted to culture and total pancreas. Because r-cell number and RNA content are known for rat islets [13,31], we can estimate the r-cell insulin mRNA copy number from the data presented S. J. Giddings et al: Extra pancreatic insulin gene expression here to range from 50-150,000 molecules per ceil. This estimate is similar to the copy numbers of other abundant mRNA's in differentiated tissues, (e. g. casein in mouse mammary gland [271, and ovalbumin in chick oviduct [28].…”