Radioimmunoassay of glucagon released from isolated guinea-pig islets of langerhans incubated in vitro

Jc, Edwards; Sl, Howell; Kw, Taylor

doi:10.1016/0304-4165(70)90028-0

Cited by 20 publications

(10 citation statements)

References 17 publications

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“…Glucagon release from isolated guinea pig islets of Langerhans incubated in vitro was unaffected by ketones (37). However, our in vivo data clearly demonstrate that physiological increases in serum ketones provoke a-cell secretion (Fig.…”

Section: Methodsmentioning

confidence: 49%

Effect of ketone bodies on glucose production and utilization in the miniature pig.

Müller¹,

Paschen²,

Seitz³

1984

J. Clin. Invest.

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As bstract. The effect of ketone bodies on glucose production (Ra) and utilization (Rd) was investigated in the 24-h starved, conscious unrestrained miniature pig. Infusing Na-DL-3-OH-butyrate (Na-DL-f-OHB) and thus shifting the blood pH from 7.40 to 7.56 resulted in a decrease of Ra by 52% and of Rd by 45%, as determined by the isotope dilution technique. Simultaneously, the concentrations of arterial insulin and glucagon were slightly enhanced, whereas the plasma levels of glucose, lactate, pyruvate, alanine, a-amino-N, and free fatty acids (FFA) were all reduced. Infusion ofNa-bicarbonate, which yielded a similar shift in blood pH, did not mimick these effects. Infusion of equimolar amounts of the ketoacid, yielding a blood pH of 7.35, induced similar metabolic alterations with respect to plasma glucose, Ra, Rd, and insulin; however, plasma alanine and a-amino-N increased.Infusing different amounts of Na-DL-3-OHB resulting in plasma steady state levels of ketones from 0.25 to 1.5 mM had similar effects on arterial insulin and glucose kinetics. No dose dependency was observed.Prevention of the Na-DL-3-OHB-induced hypoalaninemia by simultaneous infusion of alanine (1 ttmol/kg X min) did not prevent hypoglycemia.Infusion of Na-DL-l-OHB plus insulin (0.4 mU/kg in plasma glucose and Ra; however, on infusion of somatostatin plus Na-DL-3-OHB, hypoglycemia and the reduced Ra were maintained.In the anaesthetized 24-h starved miniature pig, Na-DL-3-OHB infusion decreased the hepatic exchange for glucose, lactate, and FFA, whereas the exchange for glycerol, alanine, and a-amino-N as well as liver perfusion rate were unaffected. Simultaneously, portal glucagon and insulin as well as hepatic insulin extraction rate were elevated. Leg exchange for glucose, lactate, glycerol, alanine, a-amino-N, and FFA were decreased, while ketone body utilization increased.Repeated infusion of Na-DL-3-OHB at the fourth, fifth, and sixth day of starvation in the conscious, unrestrained mini-pig resulted in a significant drop in urinary nitrogen (N)-excretion. However, this effect was mimicked by infusing equimolar amounts of Na-bicarbonate. In contrast, when only the ketoacid was given, urinary Nexcretion accelerated.To summarize: (a) Ketone bodies decrease endogenous glucose production via an insulin-dependent mechanism; in addition, ketones probably exert a direct inhibitory action on gluconeogenesis. The ketone bodyinduced hypoalaninemia does not contribute to this effect. (b) The counterregulatory response to hypoglycemia is reduced by ketones. (c) As a consequence of the decrease in Ra, glucose utilization declines during ketone infusion.(d) The insulin-stimulated MCR for glucose is not affected by ketones. (e) Ketones in their physiological moiety do not show a protein-sparing effect.

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Section: Methodsmentioning

confidence: 49%

Effect of ketone bodies on glucose production and utilization in the miniature pig.

Müller¹,

Paschen²,

Seitz³

1984

J. Clin. Invest.

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“…The effects of free fatty acids are unclear since inhibitory and stimulatory effects have been reported (see below). Ketone bodies (β-hydroxybutyrate and acetoacetate) inhibit glucagon secretion (Edwards et al 1969(Edwards et al , 1970Ikeda et al 1987). By contrast, most amino acids stimulate glucagon release, but their glucagonotropic effects vary between the different types of amino acids (Rocha et al 1972).…”

Section: Nutrientsmentioning

confidence: 94%

“…Most of the old studies performed in vivo or in vitro, and in animal species or in man, have reported clear inhibitory effects of free fatty acids (FFAs) on glucagon secretion (Edwards et al 1969(Edwards et al , 1970Gerich et al 1974bGerich et al , 1976aSeyffert and Madison 1967;Gross and Mialhe 1974;Luyckx et al 1975), but see also (Andrews et al 1975). However, more recent studies performed in vitro demonstrated glucagonotropic effects of FFA.…”

Section: Fatty Acidsmentioning

confidence: 96%

Physiological and Pathophysiological Control of Glucagon Secretion by Pancreatic α-Cells

Gilon¹,

Cheng-Xue²,

Lai³

et al. 2014

Islets of Langerhans

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“…The animals, who had free access to food until the time of the experiment, were killed by a blow on the head immediately prior to removal of the pancreas. Islets were isolated by the collagenase technique [6,7,8]. Small pieces originating from three pancreases were incubated in Hanks' solution which included 26 mg collagenase (CLS IV Worthington Biochemical Corporation, New Jersey, USA.)…”

Section: Separation Of Guinea-pig Isletsmentioning

confidence: 99%

Possible role of endogenous prostaglandins in glucagon secretion by isolated guinea-pig islets

Luyckx

Lefèbvre

1978

Diabetologia

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Previous studies have demonstrated that prostaglandins stimulate glucagon secretion in vitro and in vivo. The present work was aimed at investigating the influence of two inhibitors of prostaglandin synthesis, isopropyl-2 nicotinoyl-3 indole (L8027) and indomethacin, on basal and arginine- or noradrenaline-stimulated glucagon release from isolated guinea-pig islets incubated in the absence of glucose. L8027 (10(-4) and 10(-5) mol/l) did not alter basal glucagon release, blocked almost completely the glucagon response to arginine (10(-2) mol/l), had no effect on the glucagon release induced by noradrenaline (10(-4) mol/l), but reduced the stimulatory effect of a lower concentration of noradrenaline (5.10(-7) mol/l). The kinetic study of this inhibitory effect demonstrated that (1) it necessitates preincubation of the islets with L8027 for 30 minutes before the addition of arginine, (2) after a short preincubation period (30 minutes) in the presence of L8027, removal of the inhibitor at the time of arginine stimulation resulted in enhanced glucagon response, (3) on the contrary, after a prolonged incubation period (75 min) with arginine and L8027, the inhibitory effect remained transiently detectable after removal of L8027. Indomethacin similarly blocked arginine- and noradrenaline-induced glucagon secretion. These results suggest that an intra-insular synthesis of prostaglandins is involved in the A cell response to arginine and noradrenaline.

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Radioimmunoassay of glucagon released from isolated guinea-pig islets of langerhans incubated in vitro

Cited by 20 publications

References 17 publications

Effect of ketone bodies on glucose production and utilization in the miniature pig.

Effect of ketone bodies on glucose production and utilization in the miniature pig.

Physiological and Pathophysiological Control of Glucagon Secretion by Pancreatic α-Cells

Possible role of endogenous prostaglandins in glucagon secretion by isolated guinea-pig islets

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