Effects of Adrenergic and Cholinergic Agents Upon Insulin Secretion<i>in Vitro</i>

Malaisse, Willy; Malaisse‐Lagae, Francine; Wright, Paul J.; Ashmore, James

doi:10.1210/endo-80-5-975

Cited by 254 publications

(80 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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“…Direct stimulation of the pancreatic islets through their vagal innervation seems most likely as both fl-adrenergic and cholinergic stimulation of pancreatic islets enhances insulin release [15][16][17][18]. However involvement of a humoral loop through stimulation of gastro-intestinal hormone release cannot be entirely dismissed.…”

Section: Discussionmentioning

confidence: 99%

Early insulin release following suckling in neonatal lambs and rabbits

Porter

Bassett

1979

Diabetologia

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“…It has been known for some time that both stimulation of parasympathetic nerves and direct application of acetylcholine (ACh) stimulate insulin release [3][4][5] and glucose-induced electrical activity [6].…”

Section: Introductionmentioning

confidence: 99%

Muscarinic receptor modulation of glucose‐induced electrical activity in mouse pancreatic B‐cells

Santos

Rojas

1989

FEBS Letters

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Acetyicholine (1-10/zM) depolarized the membrane and stimulated glucose-induced bursts of electrical activity in mouse pancreatic B-cells. The acetylcholine effects were mimicked by muscarine while nicotine had no effect on membrane potential. Pirenzepine, an antagonist of the classical M l-type muscarinic receptors, but not gallamine (1-100 gM), an antagonist of the classical M2-type receptors, antagonized the acetylcholine action on glucose-induced electrical activity (ICs0 =0.25/zM). Bethanechol, an agonist of the classical M2-type musearinic receptors, was approximately 100 times less effective than acetylcholine in stimulating the electrical activity. In addition, acetylcholine (1/~M) induced a marked increase (25%) in input resistance to the B-cell membrane. The results indicate that acetylcholine exerted its effects on the B-cell membrane by inhibiting K + conductance via activation ofa musearinic receptor subtype distinct from the classical M2-type receptor.

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Effects of Adrenergic and Cholinergic Agents Upon Insulin Secretionin Vitro

Cited by 254 publications

References 1 publication

Insulin secretion by a transplantable rat islet cell tumour

Insulin secretion by a transplantable rat islet cell tumour

Early insulin release following suckling in neonatal lambs and rabbits

Muscarinic receptor modulation of glucose‐induced electrical activity in mouse pancreatic B‐cells

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