Effect of islet hormones on secretin-stimulated exocrine secretion in isolated perfused rat pancreas

Abstract

To clarify the effect of islet hormones on pancreatic ductular cell function, we measured the exocrine secretion elicited by 10 pM secretin in the presence or absence of islet hormones using an isolated perfused rat pancreas model. Insulin significantly increased secretin-stimulated pancreatic juice secretion, but not protein secretion. The potentiating effect of insulin on pancreatic juice secretion was concentration-dependent, and the maximal effect was observed with 1 microM insulin. Ouabain, a specific Na+,K(+)-ATPase inhibitor, caused concentration-dependent inhibition of the potentiating effect of insulin without affecting secretin action. Glucagon (100 nM) significantly inhibited secretin-stimulated pancreatic juice secretion and also tended to inhibit protein secretion. A somatostatin analog, SMS 201-995 (10 nM) significantly inhibited both the pancreatic juice and protein secretion stimulated by secretin. The inhibitory effect of SMS 201-995 was concentration-dependent and was maximal at 1-10 nM. These results demonstrate that insulin potentiates the secretory response to secretin, at least partly by increasing Na+,K(+)-ATPase activity, whereas glucagon and somatostatin inhibit this response. Thus, pancreatic islet hormones regulate the secretory function of pancreatic ductular and centroacinar cells.

Insulin stimulates cationic amino acid transport activity in the isolated perfused rat pancreas

“…Although earlier studies of amino acid transport in pancreatic fragments and acini failed to demonstrate a regulatory role for insulin (Bieger, Weicker & Haymovits, 1979;Korc, Iwamoto, Sankaran, Williams & Goldfine, 1981), glucose and neutral amino acid transport, protein synthesis and exocrine secretion are stimulated by insulin (see Williams & Goldfine, 1985;Norman & Mann, 1987). Endogenous insulin, released in response to a vascular glucose challenge, potentiates cholecystokinin (CCK)-induced pancreatic secretion (Saito et al 1980), and exogenous insulin has been shown to increase secretin-stimulated pancreatic juice secretion (Hasegawa, Okabayashi, Koide, Kido, Okutani, Matsushita, Otsuki & Kasuga, 1993). Moreover, concentrations of insulin antiserum, known to abolish postprandial increases in plasma insulin, have been found to inhibit CCK-and secretin-mediated pancreatic secretion (Lee, Zhou, Ren, Chang & Chey, 1990;Lee, Lee, Kim, Chang & Chey, 1994).…”

Association between Endocrine Pancreas and Ductal System. More than an Epiphenomenon of Endocrine Differentiation and Development?

“…Insulin has a direct stimulatory action on fluid secretion. In isolated perfused rat pancreas, insulin significantly increases secretin-stim-Bertelli, Bendayan ulated pancreatic juice secretion, but not protein secretion (Hasegawa et al 1993). Anti-insulin antibodies, on the other hand, reduce spontaneous fluid secretion and suppress the increase evoked by a meal or by secretin/CCK infusion (Lee et al 1990).…”

“…However, the real physiological importance of this action is far from being established (Chey 1993). In isolated rat pancreas, glucagon significantly inhibits secretin-stimulated pancreatic juice secretion (Hasegawa et al 1993). In conscious rats, glucagon reduces caerulein-evoked pancreatic secretion in terms of the volume of pancreatic juice, bicarbonate, and protein output (Biedzinski et al 1987).…”

“…It inhibits secretin-induced pancreatic juice secretion in rat perfused pancreas (Hasegawa et al 1993) and reduces cyclic AMP increase in isolated guinea pig interlobular pancreatic ducts and in cultured duct epithelial monolayers (de Ondarza and Hootman 1995). Studies specifically designed to identify somatostatin receptors in duct cells have not been carried out.…”

“…They are no less important than the islet or acinar cells, insofar as they do not merely shape excretory ducts but in fact represent a third secretory component of the gland. Functional dealings between islets of Langerhans and ducts have been investigated particularly for the effects exerted by major islet hormones on fluid and bicarbonate secretion (reviewed in Case and Argent 1993;Hasegawa et al 1993). This type of study was almost abandoned 10 years ago.…”