Inhibition by somatostatin of insulin release from isolated pancreatic islets

Okamoto, Hiroshi; Noto, Yutaka; Miyamoto, Susumu; Mabuchi, Hiroshi; Takeda, Ryoyu

doi:10.1016/0014-5793(75)81080-5

Cited by 36 publications

(14 citation statements)

References 10 publications

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“…The doses that were effective (1-10 ug/ml) were similar to those used in the perfused rat pancreas to inhibit insulin release (14). Furthermore, unlike the contradictory results concerning the disappearance of the release-suppressing effect of somatostatin (14,46,48,63) in isolated islets, the inhibition of insulin biosynthesis and the release-suppressing effect were still present in our isolated islets obtained after a brief exposure to low doses of collagenase. This observation suggests a direct effect of somatostatin on the beta cell.…”

mentioning

confidence: 47%

Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin.

García¹,

Jarrousse²,

Rosselin³

1976

J. Clin. Invest.

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A B S T R A C T The purpose of the present study was to investigate the regulation of insulin biosynthesis during the perinatal period. The incorporation of [3H]leucine into total immunoreactive insulin (IRI) and into IRI fractions was measured by a specific immunoprecipitation procedure after incubation, extraction, and gel filtration in isolated 3-day-old rat pancreases without prior isolation of islets. IRI fractions were identified by their elution profile, their immunological properties, and their ability to compete with the binding of "I-insulin in rat liver plasma membranes. No specific incorporation of [3H]leucine was found in the IRI eluted in the void volume, making it unlikely that this fraction behaves as a precursor of (pro)insulin in this system. In all conditions tested, the incorporation of [8H]leucine was linearly correlated with time. Optimal concentration of glucose (11 mM cose and was not modified by any further increase in glucose concentrations up to 27.5 mM. Theophylline or dbcAMP at 10 mM concentration did not reverse the somatostatin inhibitory effect on either insulin biosynthesis or release. Somatostatin also inhibited both processes in isolated islets from the 3-day-old rat pancreas. High Ca"+ concentration in the incubation medium reversed the inhibitory effect of somatostatin on glucoseinduced insulin biosynthesis as well as release. In both systems the inhibitory effect of somatostatin on insulin biosynthesis and release correlated well. Glipizide (10-100 ,M) and tolbutamide (400 ELM) inhibited the stimulatory effect of glucose, dbcAMP, and theophylline on [8H]leucine incorporation into IRI. The concentrations of glipizide that were effective in inhibiting [3H]leucine incorporation into IRI were smaller than those required to inhibit the phosphodiesterase activity in isolated islets of 3-day-old rat pancreas.These data suggest the following conclusions: (a) the role of the cAMP-phosphodiesterase system on insulin biosynthesis is likely to be greater in newborns than in adults; (b) the greater effectiveness of glucose and the cAMP system on insulin biosynthesis than on insulin release might possibly be related to the rapid accumulation of pancreatic IRI which is observed in the perinatal period; (c) somatostatin, by direct interaction with the endocrine tissue, can inhibit glucose and cAMPinduced insulin biosynthesis as well as release; calcium reverses this inhibition; (d) sulfonylureas inhibit insulin biosynthesis in newborn rat pancreas an effect which has

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mentioning

confidence: 47%

Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin.

García¹,

Jarrousse²,

Rosselin³

1976

J. Clin. Invest.

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“…When an excess amount of albumin or a protease inhibitor, aprotinin, was added to the medium for collagenase-treatment of rat pancreas, islets with considerable secreting ability were obtained (4). It was further observed that reduction of the incubation period with collagenase elevated that capability.…”

Section: Isolation Of Langerhans Islets From Rat Pancreasmentioning

confidence: 97%

“…Results represent the mean --+ S.E. in #U of insulin released in 4 incubation flasks (4). A flask contained 6 isolated islets.…”

Section: Isolation Of Langerhans Islets From Rat Pancreasmentioning

confidence: 99%

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Regulation of proinsulin synthesis in pancreatic islets and a new aspect to insulin-dependent diabetes

Okamoto

1981

Mol Cell Biochem

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146

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“…Fifteen islets, prepared from normal male Wistar rat pancreas by the collagenase digestion method [9], were preincubated at 37°C for 45 min in 25 ~1 KrebsRinger bicarbonate solution [ 10,l l] supplemented with 20 mM glucose. To this preincubated mixture 25 fi Krebs-Ringer bicarbonate solution, containing 5 yCi [3H]leucine, was added and the incubation was further continued at 37°C for 1.25-10 min.…”

Section: Experiments With Isolated Pancreatic Isletsmentioning

confidence: 99%

Synthesis of preproinsulin with RNA preparation of streptozotocin‐nicotinamide induced B‐cell tumor

Itoh

Okamoto

1977

FEBS Letters

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Inhibition by somatostatin of insulin release from isolated pancreatic islets

Cited by 36 publications

References 10 publications

Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin.

Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin.

Regulation of proinsulin synthesis in pancreatic islets and a new aspect to insulin-dependent diabetes

Synthesis of preproinsulin with RNA preparation of streptozotocin‐nicotinamide induced B‐cell tumor

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