Tris (Hydroxymethyl) Aminomethane (THAM) Induced Stimulation of Insulin Release by Islets of Langerhans Previously Isolated from Rat Pancreas

Rat pancreas perfusion was performed to study the effects of pituitary adenylate cyclase activating polypeptide (PACAP) on pancreatic hormone release. Under the perfusate glucose concentration of 5.5 mmol/l, 0.1 nmol/l PACAP27 significantly stimulated both insulin and glucagon release. The degree of stimulation was in a dose dependent manner. The stimulation of insulin release was clearly dependent on the perfusate glucose concentration, when compared with 2.8, 5.5 and 8.3 mmol/l. The potency of PACAP38 on the stimulation of insulin release was greater than that of PACAP27 at 5.5 mmol/l of perfusate glucose concentration, but not at 8.3 mmol/l. No differences for glucagon and cAMP release were found between the two peptides. PACAP's stimulatory effects on insulin and glucagon release were completely abolished by an equimolar and ten times lower concentration of somatostatin, respectively. The physiologic significance of these potent effects of PACAP's islet hormones release must be clarified by further studies.

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Studies on the interaction of staphylococcal δ-haemolysin with isolated islets of Langerhans

Biochemical Journal ◽

10.1042/bj2040111 ◽

1982 ◽

Vol 204 (1) ◽

pp. 111-125 ◽

Cited By ~ 3

Author(s):

N G Morgan ◽

W Montague

Keyword(s):

Insulin Release ◽

Islets Of Langerhans ◽

Culture Media ◽

Islet Cells ◽

Phosphodiesterase Inhibitor ◽

Maximal Response ◽

Artificial System ◽

Small Surface ◽

Dose Dependent ◽

Stimulation Of

delta-Haemolysin, a small surface-active polypeptide purified from the culture media of Staphylococcus aureus, was observed to stimulate the release of insulin from isolated rat islets of Langerhans. This effect was dose-dependent and saturable, with the half-maximal response elicited by a delta-haemolysin concentration of 10 micrograms/ml. Stimulation of insulin release by delta-haemolysin (10 micrograms/ml) was not dependent on the presence of glucose in the incubation medium, but was augmented by increasing concentrations of the sugar. The release of insulin in response to delta-haemolysin could be inhibited by depletion of extracellular Ca2+ or by adrenaline (epinephrine) (10 microM) and was readily reversible when delta-haemolysin was removed from the medium. In addition, the response was potentiated by incubation with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.2 mM). These observations suggest that delta-haemolysin induced a true activation of the beta-cell secretory mechanism. Stimulation of islets of Langerhans with delta-haemolysin was found to be associated with a modest increase in intracellular cyclic AMP levels, although the adenylate cyclase activity of islet homogenates was not increased by delta-haemolysin. delta-Haemolysin was observed to induce a dose-dependent net accumulation of 45Ca2+ by islet cells and to stimulate the efflux of 45Ca2+ from preloaded islets. The efflux of 45Ca2+ was modest in size and short-lived, but dramatically increased in medium depleted fo 40Ca2+. Incubation in the presence of verapamil augmented delta-haemolysin-induced 45Ca2+ efflux and insulin secretion. delta-Haemolysin was found to be a potent 45Ca2+-translocating ionophore in an artificial system. This response was dose-dependent and could be augmented by verapamil. In addition, phosphatidylcholine (25 micrograms/ml) was found to inhibit both delta-haemolysin induced 45Ca2+ translocation and insulin release in a precisely parallel manner. These studies suggest that the ability of delta-haemolysin to stimulate insulin release may be due, in part, to the facilitation of Ca2+ entry into the beta-cells of islets of Langerhans, mediated directly by an ionophoretic mechanism.

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Action of cholecystokinin analogues on exocrine and endocrine rat pancreas

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1986.250.4.g405 ◽

1986 ◽

Vol 250 (4) ◽

pp. G405-G411

Author(s):

M. Otsuki ◽

Y. Okabayashi ◽

A. Ohki ◽

T. Oka ◽

M. Fujii ◽

...

Keyword(s):

Amino Acid ◽

Insulin Release ◽

Pancreatic Enzyme ◽

Exocrine Secretion ◽

Amino Acid Residues ◽

Isolated Perfused Pancreas ◽

Pancreatic Acini ◽

Rat Pancreas ◽

Pancreatic Exocrine ◽

Stimulation Of

In the present study we have examined the abilities of cholecystokinin-(26-33)-amide [CCK-(26-33)-NH2, CCK-8], nonsulfated CCK-(26-33)-NH2 (desulfated CCK-8), CCK-(30-33)-NH2 (CCK-4), CCK-(26-33)-OH (deamidated CCK-8), and succinyl CCK-(27-31)-NH2 (Suc-Des-Asp6,Phe7-CCK-7) to stimulate exocrine pancreatic secretion from both isolated pancreatic acini and isolated perfused pancreas. We have also compared this action with their ability to cause insulin release. The modification of either the N- or C-terminal amino acid residues of CCK-8 decreased in potency, but the magnitude of the stimulation of enzyme secretion caused by a maximally effective peptide concentration was the same. The minimal effective concentration of CCK-8, desulfated CCK-8, and CCK-4 for insulin release from the isolated rat pancreas in the presence of 8.3 mM glucose was the same as that for pancreatic exocrine secretion. In contrast, the concentrations of deamidated CCK-8 and Suc-Des-Asp6,Phe7-CCK-7 required to produce insulin release were 5-10 times higher than those required to cause stimulation of pancreatic enzyme and juice secretion. It is concluded therefore that the N-terminal 4-amino acid residues or the C-terminal 2-amino acid residues of CCK-8 are not essential for biological activity but do contribute to its potency. In addition, the C-terminal 2-amino acid residues and an amide group in the C-terminal phenylalanine residue of CCK-8 appear to be important determinants of the insulin-releasing activity of the CCK peptides.

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