Unchanged Arginine-Induced Stimulation of Insulin, Glucagon, Growth Hormone, and Prolactin after Pretreatment with Indomethacin in Normal Man*

Vierhapper, H.; Bratusch-Marrain, P.; Waldhäusl, W.

doi:10.1210/jcem-50-6-1131

Cited by 19 publications

(4 citation statements)

References 23 publications

(25 reference statements)

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“…Blood glucose, plasma NEFA, C-peptide, insulin and glucagon were totally unaffected by the two doses of indomethacin, both in the basal state and during the differing rates of arginine infusion. This observation is in agreement with the results of a similar study performed in healthy volunteers [33] but are in sharp contrast with those of studies in vitro which showed that indomethacin abolishes arginine-induced glucagon secretion by isolated guinea-pig islets [18,21]. A possible explanation for this discrepancy between the studies in vivo and in vitro is the fact that plasma concentrations of indomethacin in the present study were in the range of 10 nmol/ml and about 90% of the drug in the circulation is bound to plasma albumin and thus biologically unavailable.…”

Section: Discussionsupporting

confidence: 93%

Failure of indomethacin to affect arginine-induced C-peptide and glucagon release in insulin-treated diabetics

Luyckx

Lefèbvre

1981

Diabetologia

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Summary. Fourteen insulin-treated diabetics were submitted to an arginine infusion test performed with either 11.7 or 5.85mgkg -t min -1 arginine monohydrochloride infused during 40 rain with or without previous oral administration of a low (75 + 50 mg) or a high (75 mg + 3 mg/kg) dose of indomethacin. Blood glucose, plasma non-esterified fatty acids, insulin, C-peptide and glucagon were determined at regular intervals before, during and after the arginine infusion. These parameters were totally unaffected by the two doses of indomethacin both in the basal state and during the arginine infusions at the two loads tested. Eight subjects had a basal C-peptide level above 0.07 pmol/ml and a mean (_+ SEM) maximal rise of 0.21 + 0.04 pmol/ml during the arginine infusion, whereas the remaining six patients had virtually zero values throughout the tests. The arginineinduced plasma glucagon rise was similar for the two rates of arginine infusion; the sum of the increments in plasma glucagon averaged 877 + 120 and 647 + 92pg/ml (p > 0.1) for the high and low rates of arginine infusion, respectively. The magnitude of the blood glucose rise appeared independent of the amount of arginine infused. Confirming previous reports, we found that the blood glucose rise after arginine was three to four times higher in subjects without C-peptide than in subjects with C-peptide. The mean glucagon response did not differ significantly between subjects with or without C-peptide. Thus, residual B cell function determines the magnitude of the blood glucose rise but not the glucagon response after intravenous arginine.Key words: Insulin-treated diabetics, intravenous arginine, insulin, glucagon, C-peptide, indomethacin, prostaglandins.Exogenous prostaglandins stimulate glucagon secretion in vitro [13,25] and in vivoin animals [27] andin man [8]. Moreover, previous studies from our laboratory using isolated guinea-pig islets incubated in vitro support the view that intra-insular synthesis of prostaglandins is involved in the stimulus-secretion coupling of pancreatic A cells [17][18][19][20][21].Since suppression of glucagon secretion may be considered as a therapeutic goal of diabetic management, at least under certain conditions [14], it is of interest to investigate the possible effect of inhibitors of prostaglandin synthesis in diabetic subjects. The present work was therefore designed to investigate arginine-induced glucagon secretion in insulin-treated diabetic subjects before and after the administration of moderate or high doses of indomethacin. The influence of indomethacin on residual insulin secretion was also assessed by measuring C-peptide plasma levels during the arginine infusions. Indeed, Robertson and his group [2,22,26] have reported that blocking the synthesis of prostaglandins by sodium salicylate intravenous infusion improved the insulin response to glucose in Type 2 (insulin independent) diabetics. In addition we attempted to correlate the magnitude of the blood glucose rise induced by arginine infusion with the insulin-...

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Section: Discussionsupporting

confidence: 93%

Failure of indomethacin to affect arginine-induced C-peptide and glucagon release in insulin-treated diabetics

Luyckx

Lefèbvre

1981

Diabetologia

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“…After a 15-minute baseline period, L-arginine (30 g; 1 g/min) was infused intravenously over 30 minutes (29). Venous blood samples were taken at Ϫ15, 0, 15, 30, 45, 60, 90, and 120 minute(s) for measurement of leptin, insulin, C-peptide, glucagon, FFAs, and glucose.…”

Section: Arginine Infusionmentioning

confidence: 99%

Reduction of Plasma Leptin Concentrations by Arginine but Not Lipid Infusion in Humans

et al. 2002

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STINGL, HARALD, WOLFGANG RAFFESBERG, PETER NOWOTNY, WERNER WALDHÄ USL, AND MICHAEL RODEN. Reduction of plasma leptin concentrations by arginine but not lipid infusion in humans. Obes Res. 2002; 10:1111-1119. Objective: We examined short-term effects of arginine infusion on plasma leptin in diabetic and healthy subjects. Research Methods and Procedures: Arginine stimulation tests were performed in C-peptide negative type 1 [DM1; hemoglobin A 1c ; 7.3 Ϯ 0.3%], hyperinsulinemic type 2 diabetic (DM2; 7.6 Ϯ 0.7%), and nondiabetic subjects (CON; 5.4 Ϯ 0.1%). Results: Fasting plasma leptin correlated linearly with body mass index among all groups (r ϭ 0.61, p ϭ 0.001). During arginine infusion, peak plasma insulin was lower in DM1 than in DM2 (p Ͻ 0.05) and CON (p Ͻ 0.01). Plasma leptin decreased within 30 minutes by ϳ11% in DM1 (p Ͻ 0.001), DM2 (p Ͻ 0.01), and CON (p Ͻ 0.005), slowly returning to baseline thereafter. Plasma free fatty acids (FFAs) were higher in DM1 (0.6 Ϯ 0.1 mM) and DM2 (0.6 Ϯ 0.1 mM) than in CON (0.4 Ϯ 0.1 mM, p Ͻ 0.05) and transiently declined by ϳ50% (p Ͻ 0.05) at 45 minutes in all groups before rebounding toward baseline. To examine the direct effects of FFAs on plasma leptin, we infused healthy subjects with lipid/heparin and glycerol during fasting, and somatostatin-insulin (ϳ35 pM) -glucagon (ϳ90 ng/mL) clamps were performed. In both protocols, plasma leptin continuously declined by ϳ25% (p Ͻ 0.05) during 540 minutes without any difference between the high and low FFA conditions. Discussion: Arginine infusion transiently decreased plasma leptin concentrations both in insulin-deficient and hyperinsulinemic diabetic patients, indicating a direct inhibitory effect of the amino acid but not of insulin or FFAs.

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“…In healthy subjects a stimulatory action of ASA has been described for insulin secretion in response to intravenous glucose and arginine [5,6]. In contrast, other inhibitors of PG synthesis, such as indomethacin decrease [7,8] or fail to affect insulin secretion [9]. As to tissue sensitivity to insulin, it has recently been demonstrated that ASA, apart from enhancing insulin secretion, impairs glucose metabolism, whereas ibuprofen fails to alter glucose disposal [5].…”

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confidence: 99%

Acetyl-salicylic acid impairs insulin-mediated glucose utilization and reduces insulin clearance in healthy and non-insulin-dependent diabetic man

et al. 1985

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The effect of acetyl-salicylic acid (ASA, 3 g per day for 3 days) on glucose utilization and insulin secretion was studied in healthy volunteers and Type 2 diabetic patients using the hyperglycaemic and euglycaemic insulin clamp technique. When in healthy subjects arterial plasma glucose was acutely raised and maintained at +7 mmol/l above fasting level, the plasma insulin response was enhanced by ASA (70 +/- 7 vs. 52 +/- 7 mU/l), whereas the plasma C-peptide response was identical. Despite higher insulin concentrations, glucose utilization was not significantly altered (control, 61 +/- 7; ASA, 65 +/- 6 mumol X kg-1 X min-1) indicating impairment of tissue sensitivity to insulin by ASA. Inhibition of prostaglandin synthesis was not likely to be involved in the effect of ASA, since insulin response and glucose utilization were unchanged following treatment with indomethacin. In the euglycaemic insulin (1 mU X kg-1 X min-1) clamp studies, glucose utilization was unaltered by ASA despite higher insulin concentrations achieved during constant insulin infusion (103 +/- 4 vs. 89 +/- 4 mU/l). In Type 2 diabetic patients, fasting hyperglycaemia (10.6 +/- 1.1 mmol/l) and hepatic glucose production (15 +/- 2 mumol X kg-1 X min-1) fell upon ASA treatment (8.6 +/- 0.7 mmol/l; 13 +/- 1 mumol X kg-1 X min-1). During the hyperglycaemic clamp study, the plasma response of insulin, but not of C-peptide, was enhanced by ASA, whereas tissue sensitivity to insulin was reduced by 30 percent.(ABSTRACT TRUNCATED AT 250 WORDS)

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Unchanged Arginine-Induced Stimulation of Insulin, Glucagon, Growth Hormone, and Prolactin after Pretreatment with Indomethacin in Normal Man*

Cited by 19 publications

References 23 publications

Failure of indomethacin to affect arginine-induced C-peptide and glucagon release in insulin-treated diabetics

Failure of indomethacin to affect arginine-induced C-peptide and glucagon release in insulin-treated diabetics

Reduction of Plasma Leptin Concentrations by Arginine but Not Lipid Infusion in Humans

Acetyl-salicylic acid impairs insulin-mediated glucose utilization and reduces insulin clearance in healthy and non-insulin-dependent diabetic man

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