Synthesis-secretion coupling of insulin: effect of aging

Synthesis-secretion coupling of insulin was measured in four age groups of perfused pancreases taken from Sprague-Dawley rats ranging in age from 2-12 months. The effect of long term (6 h) near-maximal glucose stimulation (300 mg/dl) on both insulin secretion and net insulinogenesis demonstrated an age-related increase in both parameters. Net insulinogenesis as well as total insulin secretion increased linearly as a function of aging. Compared to that in 2-month-old rats, total net insulin synthesis was more than 3-fold greater in 12-month-old rats, slightly less than 3-fold greater in 8-month-old rats, and twice as much in 4-month-old rats. Compared to that in 2-month-old rats, total glucose-stimulated insulin secretion was 3-fold greater in 12-month-old rats, approximately 2.2-fold greater in 8-month-old rats, and about 1.7-fold greater in 4-month-old rats. A shorter term (90 min) glucose stimulation at 150 mg/dl produced an age-related increase in insulin secretion which was relatively comparable to the higher glucose stimulus. Of equal importance is that fact that pancreases from the older rats exhibited the same degree of secretory responsiveness to changing glucose levels as did pancreases from the younger rats. Regardless of age, first phase insulin secretion was approximately twice as much in response to the higher glucose level as to the lower. Similarly, second phase insulin secretion was almost 3 times greater regardless of age. When normalized and reported in terms of insulin content, total insulin secretion was no different as a function of aging during the first 1 h of glucose stimulation (i.e. the first two phases of secretion), but it was significantly elevated in the third secretory phase (2-6 h) by the older rat groups. Total 6-h net insulinogenesis was also greater in the older rat groups. When normalized and reported in terms of total body weight, both insulin synthesis and total insulin secretion became comparable and showed no specific age-related difference. Thus, there is no indication that aging results in an uncoupling of relatively long term (6-h) insulin synthesis-secretion, since both glucose-induced responses parallel one another as a function of aging. Furthermore, reporting insulin secretion and synthesis on the basis of body weight, rather than age, totally normalizes synthesis-secretion coupling of insulin.