Insulin, glucagon and somatostatin in the perfused rat pancreas and the effects of HB 699 (4-(2-(5-chloro-2 metoxy-benzamido)-ethyl)-benzoic acid)

1981 ◽  
Vol 98 (4) ◽  
pp. 573-579 ◽  
Author(s):  
Suad Efendić ◽  
Franz Enzmann ◽  
Mark Gutniak ◽  
Anita Nylén ◽  
Manfred Zoltobrocki
Keyword(s):  
Benzoic Acid ◽  
Insulin Release ◽  
Basal Insulin ◽  
Glucagon Secretion ◽  
Inhibitory Effect ◽  
Glucagon Release ◽  
Stimulatory Action ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas

Abstract. HB 699 (100 μg/ml), almost identical with the left residue of the sulphonylurea glibenclamide, enhanced basal insulin and somatostatin release from the perfused rat pancreas. The compound also augmented both the early and the late insulin release stimulated by 6.7 mm glucose, while with 16.7 and 33.3 mm glucose only late insulin release was increased. Furthermore, HB699 enhanced both phases of glucose induced somatostatin release irrespective of whether 6.7, 16.7 or 33.3 mM glucose were used. As for glucagon release, HB 699 suppressed basal and arginine stimulated glucagon secretion. The present findings imply that the sulphonylurea moiety of glibenclamide is not a prerequisite for its stimulatory action on insulin and somatostatin release. It is suggested that the enhanced somatostatin release mediates the inhibitory effect of the compound on glucagon release.

STUDIES ON THE MECHANISM OF SOMATOSTATIN ACTION ON INSULIN RELEASE

1976 ◽  
Vol 81 (4) ◽  
pp. 753-761 ◽  
Author(s):  
S. Efendić ◽  
A. Claro ◽  
R. Luft
Keyword(s):  
Insulin Release ◽  
Basal Insulin ◽  
Potent Inhibitor ◽  
Glucagon Release ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas

ABSTRACT In man, 3 μg per kg per 90 min of linear somatostatin significantly inhibited basal as well as arginine induced insulin and glucagon release. One μg per kg per 90 min of somatostatin significantly inhibited basal insulin release but not basal glucagon release or arginine induced insulin and glucagon release. In the perfused rat pancreas, as little as one ng per ml of perfusate of somatostatin significantly inhibited arginine induced insulin but not glucagon release, while 10 ng per ml of somatostatin by more than 50 per cent reduced the effect of arginine on insulin and glucagon release. Thus, linear somatostatin seemed to be a slightly more potent inhibitor of insulin than of glucagon release in man and in the perfused rat pancreas.

Mechanism of sympathetic neural regulation of insulin, somatostatin, and glucagon secretion

1990 ◽  
Vol 258 (1) ◽  
pp. E220-E227 ◽  
Author(s):  
T. Kurose ◽  
Y. Seino ◽  
S. Nishi ◽  
K. Tsuji ◽  
T. Taminato ◽  
...  
Keyword(s):  
Glucagon Secretion ◽  
Fold Increase ◽  
Splanchnic Nerve ◽  
Stimulatory Action ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas ◽  
Adrenergic Mechanism ◽  
Adrenergic Activation ◽  
Splanchnic Nerve Stimulation ◽  
Stimulation Of

The effects of electrical stimulation of the left splanchnic nerve on insulin, somatostatin, and glucagon secretion from the isolated perfused rat pancreas were investigated. Electrical splanchnic nerve stimulation (SNS), performed by square-wave impulses, produced a 25% decrease in effluent flow and a 10-fold increase in perfusate norepinephrine. Both insulin and somatostatin output in the presence of 16.7 mM glucose were inhibited during SNS by 85 and 56% of the basal value, respectively. Glucagon output in the presence of 5.5 mM glucose was stimulated 20-fold by SNS. Perfusion with 10(-6) M propranolol further decreased insulin and somatostatin output during SNS, when expressed as the total decrement beneath basal during stimulation. The glucagon response to SNS tended to be enhanced, although not significantly, by simultaneous infusion of 10(-6) M propranolol. However, 10(-6) M phentolamine (Phe) attenuated the SNS-induced inhibition of insulin and somatostatin output by 50 and 40%, respectively. However, insulin output remained decreased after SNS with Phe. The SNS-induced glucagon response was completely abolished by 10(-6) M Phe alone or by 10(-6) M Phe plus 10(-6) M propranolol. With 10(-6) M Phe plus 10(-6) M propranolol, insulin and somatostatin output remained decreased after SNS. These results suggest that insulin and somatostatin secretions induced by glucose are inhibited during SNS through the alpha-adrenergic mechanism and also that the beta-adrenergic mechanism exerts a stimulatory action. SNS-induced glucagon secretion occurs mainly through alpha-adrenergic activation.(ABSTRACT TRUNCATED AT 250 WORDS)

STUDIES ON THE INHIBITORY EFFECT OF SOMATOSTATIN ON GLUCOSE INDUCED INSULIN RELEASE IN THE ISOLATED PERFUSED RAT PANCREAS

1975 ◽  
Vol 78 (3) ◽  
pp. 510-515 ◽  
Author(s):  
S. Efendić ◽  
R. Luft
Keyword(s):  
Insulin Release ◽  
Response Curve ◽  
Insulin Dose ◽  
Inhibitory Effect ◽  
Hormone Release ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas ◽  
Isolated Perfused Rat Pancreas ◽  
The Right ◽  
Competitive Nature

ABSTRACT Somatostatin, the recently discovered growth hormone release-inhibiting hormone in the hypothalamus, also inhibited glucose induced insulin release from the isolated perfused rat pancreas. The lowest effective dose of somatostatin was 1 ng/ml of perfusate. By increasing the dose to 100 ng/ml an almost complete inhibition of basal as well as stimulated insulin release was obtained. The inhibition of glucose stimulated insulin release mediated by somatostatin might be of competitive nature since somatostatin seemed to dislocate the glucose-insulin dose-response curve to the right.

Stimulatory effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on insulin and glucagon release from the isolated perfused rat pancreas

1993 ◽  
Vol 129 (5) ◽  
pp. 473-479 ◽  
Author(s):  
Chizuko Yokota ◽  
Koichi Kawai ◽  
Shinichi Ohashi ◽  
Yasuko Watanabe ◽  
Seiji Suzuki ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Dependent Manner ◽  
Glucagon Release ◽  
Perfused Rat Pancreas ◽  
Pancreas Perfusion ◽  
Rat Pancreas ◽  
Pituitary Adenylate Cyclase ◽  
Stimulation Of

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.

Alpha-2 adrenergic agonism stimulates islet glucagon release from perfused rat pancreas: possible involvement of alpha-2A adrenergic receptor subtype

1992 ◽  
Vol 127 (3) ◽  
pp. 279-283 ◽  
Author(s):  
Hiroshi Hirose ◽  
Hiroshi Maruyama ◽  
Katsuhiko Itoh ◽  
Kazunori Koyama ◽  
Koichi Kido ◽  
...  
Keyword(s):  
Insulin Release ◽  
Adrenergic Receptor ◽  
Receptor Subtype ◽  
Glucagon Release ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas ◽  
Selective Antagonist ◽  
Alpha Adrenoceptor ◽  
Selective Agonists ◽  
Subtype Selective

Although insulin release is known to be inhibited by alpha-2 adrenergic agonism, the effect of alpha adrenergic agonism on islet glucagon release remains controversial. Alpha-2 adrenoceptors are subdivided into alpha-2A and alpha-2B subtypes using receptor binding methods or cloning methodology. This study was designed to confirm the involvement of the alpha-2 adrenoceptor and its subtypes in glucagon release from the isolated, perfused rat pancreas. Both the alpha-2A preferential agonist oxymetazoline and the non-subtype-selective alpha-2 agonist clonidine induced concentration-dependent stimulation of glucagon release, starting at 10−8 and 10−7 mol/l, respectively (p<0.01). In contrast, neither of the two alpha-1 selective agonists, methoxamine and phenylephrine, at concentrations up to 10−6 mol/l affected glucagon release. Furthermore, the non-subtype-selective alpha-2 antagonist rauwolscine at concentrations of 10−6 and 10−5 mol/l and the alpha-1 and alpha-2A selective antagonist WB-4101 at 10−5 mol/l showed significant antagonism of 10−7 mol/l clonidine-induced glucagon release versus corresponding controls. Neither the alpha-1 and alpha-2B selective antagonist prazosin nor the alpha-2B preferential antagonist chlorpromazine, at concentrations up to 10−5 mol/l, antagonized the effects of clonidine. None of the eight drugs, at the concentrations tested, affected insulin release with 5.5 mmol/l glucose. These results suggest that in rats islet glucagon release induced by alpha adrenoceptor agonism is mediated through alpha-2 adrenoceptors, possibly the alpha-2A subtype.

Sign in / Sign up

Export Citation Format

Share Document