Evidence of Extrapancreatic Glucagon Secretion in Man

Asger Lund; Jonatan I Bagger; Nicolai J Wewer Albrechtsen; Mikkel Christensen; Magnus Grøndahl; Bolette Hartmann; Elisabeth R Mathiesen; Carsten P Hansen; Jan H Storkholm; Gerrit van Hall; Jens F Rehfeld; Daniel Hornburg; Felix Meissner; Matthias Mann; Steen Larsen; Jens J Holst; Tina Vilsbøll Lauritsen; Filip K Knop

doi:10.2337/db15-1541

Evidence of Extrapancreatic Glucagon Secretion in Man

Asger Lund, Jonatan I Bagger, Nicolai J Wewer Albrechtsen, Mikkel Christensen, Magnus Grøndahl, Bolette Hartmann, Elisabeth R Mathiesen, Carsten P Hansen, Jan H Storkholm, Gerrit van Hall, Jens F Rehfeld, Daniel Hornburg, Felix Meissner, Matthias Mann, Steen Larsen, Jens J Holst, Tina Vilsbøll Lauritsen, Filip K Knop

89 Citations (Scopus)

Abstract

Glucagon is believed to be a pancreas-specific hormone, and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from a-cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy control subjects to a 75-g oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. We applied novel analytical methods of plasma glucagon (sandwich ELISA and mass spectrometry-based proteomics) and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gastrointestinal tract elicits significant hyperglucagonemia in these patients. These findings emphasize the existence of extrapancreatic glucagon (perhaps originating from the gut) in man and suggest that it may play a role in diabetes secondary to total pancreatectomy.

Original language	English
Journal	Diabetes
Volume	65
Issue number	3
Pages (from-to)	585-597
Number of pages	13
ISSN	0012-1797
DOIs	https://doi.org/10.2337/db15-1541
Publication status	Published - Mar 2016

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Lund, A., Bagger, J. I., Wewer Albrechtsen, N. J., Christensen, M., Grøndahl, M., Hartmann, B., Mathiesen, E. R., Hansen, C. P., Storkholm, J. H., van Hall, G., Rehfeld, J. F., Hornburg, D., Meissner, F., Mann, M., Larsen, S., Holst, J. J., Lauritsen, T. V., & Knop, F. K. (2016). Evidence of Extrapancreatic Glucagon Secretion in Man. Diabetes, 65(3), 585-597. https://doi.org/10.2337/db15-1541

Lund, A, Bagger, JI, Wewer Albrechtsen, NJ, Christensen, M, Grøndahl, M, Hartmann, B , Mathiesen, ER, Hansen, CP, Storkholm, JH, van Hall, G , Rehfeld, JF, Hornburg, D, Meissner, F, Mann, M, Larsen, S, Holst, JJ , Lauritsen, TV & Knop, FK 2016, 'Evidence of Extrapancreatic Glucagon Secretion in Man', Diabetes, vol. 65, no. 3, pp. 585-597. https://doi.org/10.2337/db15-1541

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title = "Evidence of Extrapancreatic Glucagon Secretion in Man",

abstract = "Glucagon is believed to be a pancreas-specific hormone, and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from a-cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy control subjects to a 75-g oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. We applied novel analytical methods of plasma glucagon (sandwich ELISA and mass spectrometry-based proteomics) and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gastrointestinal tract elicits significant hyperglucagonemia in these patients. These findings emphasize the existence of extrapancreatic glucagon (perhaps originating from the gut) in man and suggest that it may play a role in diabetes secondary to total pancreatectomy.",

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AU - Lund, Asger

AU - Bagger, Jonatan I

AU - Wewer Albrechtsen, Nicolai J

AU - Christensen, Mikkel

AU - Grøndahl, Magnus

AU - Hartmann, Bolette

AU - Mathiesen, Elisabeth R

AU - Hansen, Carsten P

AU - Storkholm, Jan H

AU - van Hall, Gerrit

AU - Rehfeld, Jens F

AU - Hornburg, Daniel

AU - Meissner, Felix

AU - Mann, Matthias

AU - Larsen, Steen

AU - Holst, Jens J

AU - Lauritsen, Tina Vilsbøll

AU - Knop, Filip K

N1 - Erratum. Evidence of Extrapancreatic Glucagon Secretion in Man. Diabetes 2016;65:585–597

PY - 2016/3

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N2 - Glucagon is believed to be a pancreas-specific hormone, and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from a-cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy control subjects to a 75-g oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. We applied novel analytical methods of plasma glucagon (sandwich ELISA and mass spectrometry-based proteomics) and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gastrointestinal tract elicits significant hyperglucagonemia in these patients. These findings emphasize the existence of extrapancreatic glucagon (perhaps originating from the gut) in man and suggest that it may play a role in diabetes secondary to total pancreatectomy.

AB - Glucagon is believed to be a pancreas-specific hormone, and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from a-cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy control subjects to a 75-g oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. We applied novel analytical methods of plasma glucagon (sandwich ELISA and mass spectrometry-based proteomics) and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gastrointestinal tract elicits significant hyperglucagonemia in these patients. These findings emphasize the existence of extrapancreatic glucagon (perhaps originating from the gut) in man and suggest that it may play a role in diabetes secondary to total pancreatectomy.

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JO - Diabetes

JF - Diabetes

IS - 3

ER -

Evidence of Extrapancreatic Glucagon Secretion in Man

Abstract

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