Comparison of Alpha- and Beta-Cell Secretory Responses in Islets Isolated with Collagenase and in the Isolated Perfused Pancreas of Rats

Norfleet, W. T.; Pagliara, Anthony S.; Haymond, Morey W.; Matschinsky, Franz M.

doi:10.2337/diab.24.11.961

Cited by 37 publications

(14 citation statements)

References 5 publications

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“…Thus, for recognition, the hexose must have an equatorial hydroxyl group at C-2. The inability of D-mannose to induce release of GLI or GLP-1 is in contrast to its ability to stimulate insulin release from pancreatic B-cells (24,25) and to suppress arginine-induced glucagon release from pancreatic A-cells (26). Even droxyl group at C-3 is replaced by a methoxy group, as in 3-0-methyl-D-glucose, the compound can stimulate the releases of GLI and GLP-1.…”

Section: Discussionmentioning

confidence: 86%

Relationship between molecular structures of sugars and their ability to stimulate the release of glucagon-like peptide-1 from canine ileal loops.

Shima

Suda

Nishimoto

et al. 1990

Acta Endocrinologica

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The structure-activity relationship of sugars inducing secretion of glucagon-like peptide-1 from the gut was examined using intestinal loops prepared from the terminal portion of the ileum of dogs. The plasma glucagon-like peptide-1 concentration in a mesenteric vein draining only the looped region of the intestine was increased after infusion of 139 mmol/l solutions of D\ x=r eq-\ glucose, D-galactose, D-glucuronic acid, 3-0-methyl-D\x=req-\ glucose, maltose, sucrose or maltitol into the intestinal lumen, but not after infusion of solutions of D-fructose, D-fucose, D-mannose, D-xylose or lactose. The increases in plasma glucagon-like peptide-1 concentration correlated with the corresponding increases in glucagon-like immunoreactivity induced by these sugars. The plasma glucose level of the regional mesenteric vein increased significantly from the basal level after instillation of D\ x=r eq-\ glucose, but not after instillation of other sugars. It is suggested that cells of the gut have a glucose sensor for release of products of the glucagon gene and that this sensor has specific steric requirements. The sugars that induced glucagon-like peptide-1 release share the molecular features of electron density near C(6), an equatorial hydroxyl at C(2), and an axial hydroxyl at C(1), which could account for their recognition by the glucose sensor to initiate the releases of glucagon-like peptide-1 and glucagon-like immunoreactivity.Gut glucagon-related peptides are distributed in enteroendocrine L cells throughout the gastroin¬ testinal tract, with highest concentrations localized in the distal small intestine and the colon (1-3). The precursor molecule proglucagon contains, in addi¬ tion to the amino acid sequence of the hormone glucagon and glicentin-related polypeptide (proglucagon(l-30)), a sequence of further 96 amino acids. The latter fragment contained two glucagon-like peptides, glucagon-like peptide (GLP)-l (proglucagon(72-108)) and glucagon-like peptide-2 (proglucagon(126-159)), which were flanked by basic dipeptides, potential post-translational cleavage sites (4,5) Proglucagon is shown to be processed into glicentin (proglucagon 1-69) (6) and the two glucagon-like peptides in the ileum. Recently, the complete amino acid sequences of human and porcine gut GLP-1 have been shown to correspond to that of proglucagon(78-107) amide (7) which was the product of further cleavage and amidation of proglucagon(72-108). A synthetic peptide corresponding to proglucagon(78-107) amide has been reported to have several interesting effects: at physiological concentrations it strongly stimulates insulin secretion (8,9) suppresses gluca¬ gon secretion (10,11), and inhibits acid secretion (12). GLP-1 immunoreactivity has been shown to be released into the circulation after a mixed meal and in response to a glucose load (13). Thus, GLP-1 has been suggested to play an important role in carbohydrate metabolism as an "incretin". How¬ ever, the mechanism of its secretion from the in¬ testinal tract is not known.To clarify this point...

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Section: Discussionmentioning

confidence: 86%

Relationship between molecular structures of sugars and their ability to stimulate the release of glucagon-like peptide-1 from canine ileal loops.

Shima

Suda

Nishimoto

et al. 1990

Acta Endocrinologica

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“…In humans, infusion of SST decreased arginine-stimulated plasma insulin and glucagon levels in a dose-dependent manner (Skamene and Patel 1984). In the isolated-perfused rat pancreas, perifused rat islets, and cultured islets, SST inhibits GSIS as well as arginine-stimulated glucagon secretion (Norfleet et al 1975;Fujimoto 1981;Bolaffi et al 1990). Recently, an additional peptide of the SST preprohormone, neuronostatin, has been identified and also found to inhibit GSIS in rat islets (Salvatori et al 2014).…”

Section: Peptide Infusionmentioning

confidence: 99%

Glicentin-related pancreatic polypeptide inhibits glucose-stimulated insulin secretion from the isolated pancreas of adult male rats

et al. 2015

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Peptides derived from the glucagon gene Gcg, for example, glucagon and glucagon‐like peptide 1 (GLP‐1), act as physiological regulators of fuel metabolism and are thus of major interest in the pathogenesis of diseases, such as type‐2 diabetes and obesity, and their therapeutic management. Glicentin‐related pancreatic polypeptide (GRPP) is a further, 30 amino acid Gcg‐derived peptide identified in human, mouse, rat, and pig. However, the potential glucoregulatory function of this peptide is largely unknown. Here, we synthesized rat GRPP (rGRPP) and a closely related peptide, rat GRPP‐like peptide (rGRPP‐LP), and investigated their actions in the liver and pancreas of adult male rats by employing isolated‐perfused organ preparations. Rat GRPP and rGRPP‐LP did not affect glucose output from the liver, but both elicited potent inhibition of glucose‐stimulated insulin secretion (GSIS) from the rat pancreas. This action is unlikely to be mediated by glucagon or GLP‐1 receptors, as rGRPP and rGRPP‐LP did not stimulate cyclic adenosine monophosphate (cAMP) production from the glucagon or GLP‐1 receptors, nor did they antagonize glucagon‐ or GLP‐1‐stimulated cAMP‐production at either receptor. GRPP and GRPP‐LP may be novel regulators of insulin secretion, acting through an as‐yet undefined receptor.

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“…Collagenase exposure may, in large part, be responsible for this observed alteration in CCK-8S sensitivity. A similar reduction in responsiveness of collagenase islets to various agents, including peptide hormones, has been previously documented (25,26). Furthermore, the physiological involvement of CCK in meal-induced insulin secretion in unstressed rats has been emphasized in a recent report (27).…”

Section: Discussionmentioning

confidence: 75%

Stimulatory Effects of Cholecystokinin on Isolated Perifused Islets Inhibited by L 364718 Potent and Specific Antagonist

Zawalich

Diaz²,

Zawalich³

1988

Diabetes

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The influence of L 364718 on islet responsiveness to sulfated cholecystokinin (CCK-8S) was investigated. In islets whose inositol-containing phospholipids were prelabeled during a 2-h incubation period, subsequent exposure to L 364718 (1 nM) significantly impaired the secretion of insulin usually noted in response to 200 nM CCK-8S in the simultaneous presence of 7 mM glucose. A higher level of the antagonist (10 nM) completely abolished insulin secretion. L 364718 (1-10 nM) reduced the efflux of 3H from myo-[2-3H]-inositol prelabeled islets in parallel with the reduction in secretion. L 364718 (10 nM) significantly reduced the accumulation of 3H-containing inositol phosphates usually noted with CCK-8S addition. L 364718, at levels 10- to 100-fold greater than those necessary to attenuate CCK-8S-induced insulin secretion, had no adverse effect on the insulin secretory response of freshly isolated islets to 10 mM glucose alone, 5 mM D-glyceraldehyde, 15 mM alpha-ketoisocaproate, or 50 ng/ml gastric inhibitory polypeptide. L 364718 (1000 nM) had no adverse influence on carbamylcholine (1 mM)-induced phosphoinositide hydrolysis. These results establish L 364718 as a potent and highly selective antagonist of cholecystokinin's stimulatory actions on beta-cells. Because of its potency, selectivity, and oral effectiveness, in vivo studies with L 364718, aimed at unraveling the pleiotropic effects of CCK-8S on glucose and insulin homeostasis, seem feasible.

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Comparison of Alpha- and Beta-Cell Secretory Responses in Islets Isolated with Collagenase and in the Isolated Perfused Pancreas of Rats

Cited by 37 publications

References 5 publications

Relationship between molecular structures of sugars and their ability to stimulate the release of glucagon-like peptide-1 from canine ileal loops.

Relationship between molecular structures of sugars and their ability to stimulate the release of glucagon-like peptide-1 from canine ileal loops.

Glicentin-related pancreatic polypeptide inhibits glucose-stimulated insulin secretion from the isolated pancreas of adult male rats

Stimulatory Effects of Cholecystokinin on Isolated Perifused Islets Inhibited by L 364718 Potent and Specific Antagonist

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