Abstract.
Aims/hypothesis:
To study the effects of a specific glucagon receptor antagonist (Bay 27–9955), on plasma glucose concentrations and rates of glucose production in response to hyperglucagonaemia in humans.
Methods:
The study was conducted as a two-dose [Low Dose Bay 27–9955 70 mg, (n = 6), High Dose Bay 27–9955 200 mg, (n = 8)], double blind, placebo controlled, crossover study. Basal glucose production was measured after an overnight fast with [6,6-2H]. At 0 min Bay 27–9955 or placebo was administeredand at 120 min an infusion of somatostatin [0.1 μg · (kg · min)–1], insulin [24 pmol · (m2· min)–1] and glucagon [3 ng · (kg · min)–1] was initiated.
Results:
Basal plasma glucose concentrations were about 5 mmol/l and basal rates of glucose production were about 13 μmol · (kg · min)–1. During the hyperglucagonaemic period, plasma glucagon concentrations doubled to 100 pg/ml, plasma glucose concentration increased by 75 % to a peak of about 10 mmol/l and glucose production doubled to about 23 μmol · (kg · min)–1 (p < 0.0001 vs basal). In the High Dose Group these effects of glucagon were markedly blunted, plasma glucose concentrations were 7.6 ± 1.1 mmol/l (p = 0.012 vs placebo) and rates of glucose production increased minimally to 15.3 ± 1.9 μmol · (kg-min)–1 (p < 0.0003 vs placebo]. In the Low Dose Group, there was a proportional decrease in the effects of Bay 27–9955 on these parameters.
Conclusion/interpretation:
Bay 27–9955 is an effective and safe glucagon antagonist in humans. Given the potentially important role of glucagon in increasing glucose production and gluconeogenesis in patients with Type II (non-insulin-dependent) diabetes mellitus this agent could represent an innovative class of therapeutic agents for the disease. [Diabetologia (2001) 44: 2018–2024]
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Received: 3 July 2001 and in revised form: 27 July 2001
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Petersen, K., Sullivan, J. Effects of a novel glucagon receptor antagonist (Bay 27–9955) on glucagon-stimulated glucose production in humans. Diabetologia 44, 2018–2024 (2001). https://doi.org/10.1007/s001250100006
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DOI: https://doi.org/10.1007/s001250100006