Uniphasic insulin responses to secretin stimulation in man

Abstract

A B S T R A C T Secretin-stimulated insulin release was studied in normal subjects. In response to rapid intravenous injections (pulses) of secretin, insulin levels reached a peak between 2 and 5 min and returned to basal levels with 15 min. In contrast to large glucose pulses, increasing secretin pulses did not elicit sustained or prolonged insulin responses. In addition, insulin responses to a pulse and infusion were essentially identical with that of a pulse alone. Increasing secretin pulses given in 1 day were associated with decreasing insulin responses but not when the same pulses of secretin were given over a 2 day period. When time was the sole variable, insulin responses progressively decreased after identical 15-U secretin pulses given every 30 min, but were unchanged when the interval was 105 min. These observations indicate that secretin in contrast to glucose stimulates insulin release which is uniphasic. They suggest that release occurs only from a stored, readily available pool. This insulin pool appears to be relatively small and can be discharged faster than it refills.

Stimulation of Insulin Secretion by Long-Chain Free Fatty Acids. A DIRECT PANCREATIC EFFECT

“…Grodsky, Landahl, Curry, and Bennett (16) suggested that this response represents the early release of preformed insulin granules followed by a slower phase of release related to de novo synthesis of insulin. The infusion of gastrointestinal hormones such as secretin, however, produces only uniphasic insulin responses (12,17).…”

Kinetics of insulin secretion to acute, repetitive stimulation of islets in vivo in sprague dawley rats

“…A study that did report β-cell exhaustion used secretin stimulation, where 35 healthy subjects with no family history of diabetes were assigned to five different protocols that included multiple pulses of secretin or glucose, at different time intervals. 9 Signs of exhaustion were evident in two groups: (1) 5 subjects that received 5 intravenous secretin injections of 10, 25, 75, 150 and 300 U, separated by 75 min intervals, and (2) 6 subjects receiving 4-15 U intravenous secretin pulses at 0, 105, 135 and 165 min.…”

“…In this study we have profiled the glucose-insulin dynamics in SD rats under 8 repeated pulses of glucose, with and without forskolin, for a period of 240 min. Previous studies in humans [5][6][7][8][9] or with isolated animal pancreata and islets 1,3,4 have not settled the issue of whether β-cells can be exhausted in vivo with physiological stimulations. As far as we know, this question has not been scrutinized in animal models, up till now.…”

Studies of secretin-stimulated insulin responses in man

“…The acute insulin responses to the four 150-U secretin pulses given at 30 min intervals progressively and significantly fell to each succeeding pulse (Table II, P < 0.05). The subsequent 5-g glucose pulse given 30 min after the final 150 U secretin pulse was associated with increased acute insulin responses (P < 0.02) and more rapid glucose disappearance rates (Table II, (4,5), it is pertinent to compare the patterns of responses during similar studies employing infusions of glucose (4), epinephrine (8), and propranolol (9). When the insulin responses to the small (15 U) secretin pulses are compared to those after a small (5 g) glucose pulse before, during, and after a glucose infusion as has been recently reported (4), important differences are readily noted.…”

“…Thus the acute insulin response to 5 g glucose was increased after secretin pretreatment (presecretin: 34.9±14.8; postsecretin: 50.5+22.5 AU/ml, P < 0.02) which suggests that INTRODUCTION Secretin stimulates insulin responses both in vitro and in vivo (1,2). In contrast to glucose-stimulated insulin responses which have been shown to be both multiphasic and multicompartmental (3,4), recent evidence suggests that secretin stimulates a characteristically uniphasic rapid insulin response derived from a small storage pool (5). The following studies were undertaken to evaluate further the mechanism of the secretin-stimulated insulin response.…”