Studies of secretin-stimulated insulin responses in man

Abstract

A B S T R A C T Recent studies have suggested that secretin, like glucose, stimulates a rapid insulin response from a small storage pool. In order to evaluate the mechanism of the secretin-stimulated insulin response, small (15 U) rapidly administered intravenous injections (pulses) of secretin were given before, during, and after a 20 hr 300 mg/min glucose infusion. Contrary to previous studies demonstrating that the acute insulin response to a small (5 g) pulse of glucose given 45 ;min after the start of the glucose infusion was significantly diminished compared to the response to the preinfusion pulse, the acute insulin response (2-5 min Aimmuno-reactive insulin IAU/ml) to 15-U secretin pulses exhibited a greater than twofold increase (before: 31.1±15.4; during: 71.2+40.4, /LU/ml, mean ±sD, P < 0.02). The increased response to secretin was also found after 20 hr of continuous glucose infusion, but was not observed 1 hr after cessation of the infusion when plasma glucose levels returned to control values. Thus, this increased response to secretin was glucose dependent.Four 150-U secretin pulses given at 30 min intervals elicited progressively and significantly diminished acute insulin responses with each succeeding pulse, consistent with depletion of the small storage pool. Similar to the observation that the magnitude of the insulin response to secretin was glucose dependent, the glucose-stimulated output appeared to be secretin dependent. 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 This work was presented in part at

Somatostatin blockade of acute and chronic stimuli of the endocrine pancreas and the consequences of this blockade on glucose homeostasis.

“…Among pharmacologic inhibitors of insulin secretion, propranolol, mannoheptulose, and 2-deoxy-glucose are not able to inhibit as many diverse stimuli for insulin release as somatostatin (25,(27)(28)(29). Diazoxide and diphenylhydantoin are widely effective inhibitors of insulin secretion (25,30), but their in vivo effectiveness does not match that of somatostatin (31,32).…”

Does Secretin Control Insulin Secretion?

“…This could also be due to the diversity of the insulin poois upon which the two substances react. Lerner and Porte (1972) suggest that glucose and secretin stimulate functionally sep-arate storage pools of insulin, but that the acute response to either stimulus is partly determined by exposure to the other. Moreover the response to glucose is biphasic, while that to secretin is uniphasic (Lerner and Porte, 1970).…”

“…The interpretation of these results was therefore difficult and controversial. Some authors tlemonstrated a stimulation in normal subjects (Dupré et al 1969;Lerner and Porte, 1972), in obese diabetics (Enk, 1976), in obese non diabetics (Enk et al, 1976) and even in diabetics (Halter and Porte, 1976), with a common insulin secretion in spite of increased threshold to glucose. In contrast other authors did not find any effect either in vitro (Telib and Pfeiffer, 1970) or in vivo (Fahrenkrug et al, 1978;O'Connor et al, 1976).…”

The Effect of the β‐Receptor Blockade (Propranolol) on the Endocrine and Exocrine Pancreatic Function in Man after the Administration of Intestinal Hormones (Secretin and Cholecystokinin‐Pancreozymin)

“…As a stimulation of the a-receptor leads to an inhibition, and the stimulation of the ,B-receptor leads to a rise in insulin secretion (Porte, 1967), the inhibiting effect of adrenalin is probably due to its predominant stimulation of the a-receptor. Recently Lerner and Porte (1972) found that neither epinephrine nor propranolol have an effect on secretin-induced insulin secretion. The fact that Lerner injected a different amount of SC from us, and also that his investigation conditions were slightly different (Lerner gave the second SC injection 55 min.…”