Inhibition of Insulin Secretion by Somatostatin

Alberti, K. G. M. M.; Christensen, N. J.; Christensen, Søren; Hansen, Aa. Prange; Iversen, Johan; Lundbæk, K; Seyer‐Hansen, K.; Ørskov, Hans

doi:10.1016/s0140-6736(73)92873-0

Cited by 474 publications

(179 citation statements)

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“…Finally, reduction of insulin release by the tumour in response to leucine plus theophylline was achieved using either adrenaline or somatostatin. Both agents inhibit insulin secretion by islet tissue [36][37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Insulin secretion by a transplantable rat islet cell tumour

et al. 1981

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Summary. Investigation of the subcellular and molecular components of insulin secretion has been made difficult by the small quantities of material available. The recent development of a transplantable rat islet cell tumour of high insulin content and state of differentiation suggested a system more amenable to analysis. To validate the tumour as a model of secretion we have studied its release of insulin. In acute experiments in vitro immunoreactive insulin release was increased by leucine, glucagon, theophylline and dibutyryl cyclic AMP, though not by glucose. Leucine (20 mmol/1) plus theophylline (5 mmol/1) caused an abrupt, sustained and rapidly reversible stimulation of two-to fivefold. The response was inhibited by antagonists of cellular oxidative phosphorylation (cyanide, 2,4--dinitrophenol, antimycin A), calcium flux (EGTA, verapamil, Mg2 § calmodulin (trifluoperazine), microtubules (vinblastine, colchicine) and by adrenaline and somatostatin. These findings suggest that the tumour secretes insulin by an exocytotic mechanism similar to that of normal islet tissue. Key words: Islet cell tumour, B cell, insulin secretionThe pancreatic B cell has proved difficult to investigate at the subcellular and molecular levels. The classical strategy of subcellular fractionation, purification and reassembly has been greatly hindered by the shortage of starting material [3,4]. In this context the description recently of a transplantable rat islet cell tumour is of considerable interest. The tumour contains large amounts of insulin and consists predominantly of well-granulated cells the morphology of which closely resembles that of rat B cells [1,2].That this islet cell tumour might offer a largescale model of insulin secretion is an attractive possibility. Realisation of this potential, however, depends upon establishing that the tumour is indeed capable of the exocytosis of insulin. We here report a series of experiments in which the characteristics of insulin release by the turnout were defined. The effect of putative secretagogues, the dynamics of insulin release, and the influence of potentiators and inhibitors of secretion are described. Materials and MethodsThe islet cell tumour [1, 2] was maintained by serial subcutaneous transplantation within a colony of inbred albino NEDH strain rats [2]. BuffersTissue was handled in a Krebs Ringer solution [5] containing NaC1 115mmol/1, KC1 5.0mmol/1, NaI-ICO 3 24mmol/1, MgC12 1.0 mmol/1 and CaC12 2.5 mmol/1, freshly equilibrated with 5% CO 2 95% 02. Except where specified glucose 2.8 mmol/l, bovine plasma albumin (Armour Pharmaceuticals, Eastbourne, UK) 1.0 mg/ml, and 5.0 mmol/1 each of sodium pyruvate, monosodium glutamate and disodium fumarate were included (using 95 mmol/l NaC1 to maintain the final sodium ion concentration at 139 mmol/ 1). When individual experiments required further additions the osmolality of control buffers was balanced using sucrose.Chemicals were purchased from Fisons Scientific Apparatus, Loughborough, UK and British Drug House Chemicals, Poole,...

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Section: Discussionmentioning

confidence: 99%

Insulin secretion by a transplantable rat islet cell tumour

et al. 1981

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“…A third level of sociologic organisation was recognised in the interactions of pancreatic B cells with environmental signals That the secretory function of B cells may be influenced by products from surrounding islet non-B cells was already suggested in the sixties by Young [73] and by Samols et al [74] for glucagon, and by Lernmark and Hellman [75] for an inhibitory islet substance later identified as somatostatin [76,77]. Experimental evidence for both types of indirect islet cell interactions has been largely indirect and controversial [50].…”

Section: Synergistic Interaction With Environmental Signalsmentioning

confidence: 99%

The biosociology of pancreatic B cells

1987

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“…While investigating the effect of somatostatin on GH release, several groups made the unexpected observation that the peptide also inhibited insulin release [1,57,35,39,69,18,32,33,62,29,34]. This was particularly interesting in view of the hypothesis that impaired insulin release is a primary derangement in diabetes mellitus.…”

Section: On Endocrine Functionsmentioning

confidence: 99%