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Glucose-dependent insulinotropic polypeptide is a pancreatic polypeptide secretagogue in humans

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@article{1b4f1ab887724062bd0f0ee985e78f82,
title = "Glucose-dependent insulinotropic polypeptide is a pancreatic polypeptide secretagogue in humans",
abstract = "BACKGROUND: Glucose-dependent insulinotropic polypeptide(GIP) has been suggested to stimulate the secretion of pancreatic polypeptide(PP), an islet hormone thought to regulate gut motility, appetite and glycemia.OBJECTIVE: To determine whether human GIP1-42 (hGIP) stimulates PP secretion.METHOD: As glycemia modulates the secretion of PP, we measured plasma PP concentrations from two studies in healthy men(n=10) and in patients with type 2 diabetes (T2D)(n=12), where hGIP1-42 had been administered intravenously during fasting glycemia, hyperglycemia(12mmol/L) and insulin-induced hypoglycemia (targets: 2.5mmol/L(healthy)/3.5mmol/L(T2D)). Porcine GIP1-42 (pGIP) was also infused intra-arterially in isolated porcine pancreata(n=4).RESULTS: Mean fasting plasma glucose concentrations were ~5mmol/L(healthy) and ~8mmol/L(T2D).At fasting glycemia, PP concentrations were higher during intravenous hGIP1-42 infusion compared with saline in healthy men (mean(SEM), net iAUCs0;30min 403(116) vs. -6(57) pmol/L×min,p=0.004) and in patients with T2D (905(177) vs. -96(86)pmol/L×min,p=0.009). During hyperglycemic clamping, PP concentrations were significantly higher during hGIP1-42 infusion compared with saline in patients with T2D (771(160) vs. -183(117)pmol/L×min,p=0.001), but not in healthy individuals (-8(86) vs. -57(53)pmol/L×min,p=0.69). When PG levels were declining in response to exogenous insulin, PP concentrations were higher during hGIP1-42 infusion compared with saline in healthy individuals (294(88) vs. -82(53)pmol/L×min,p=0.0025), but not significantly higher in patients with T2D(586(314) vs. -120(53),p=0.070). At target hypoglycemia , PP levels surged in both groups during both hGIP1-42 and saline infusions.In isolated pancreata, pGIP1-42 increased PP output in the pancreatic venous effluent (baseline vs. infusion, 24(5) vs. 79(16)pmol/min x min,p=0.044).CONCLUSION: GIP1-42 increases plasma PP secretion in healthy individuals, patients with T2D and isolated porcine pancreata. Hyperglycemia blunts the stimulatory effect of hGIP1-42 in healthy individuals, but not in patients with T2D.",
author = "Simon Veedfald and Louise Vedtofte and Kirsa Skov-Jeppesen and Deacon, {Carolyn F} and Bolette Hartmann and Tina Vilsb{\o}ll and Knop, {Filip K} and Christensen, {Mikkel B} and Holst, {Jens J}",
note = "{\circledC} Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2019",
month = "10",
day = "26",
doi = "10.1210/clinem/dgz097",
language = "English",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The/Endocrine Society",

}

RIS

TY - JOUR

T1 - Glucose-dependent insulinotropic polypeptide is a pancreatic polypeptide secretagogue in humans

AU - Veedfald, Simon

AU - Vedtofte, Louise

AU - Skov-Jeppesen, Kirsa

AU - Deacon, Carolyn F

AU - Hartmann, Bolette

AU - Vilsbøll, Tina

AU - Knop, Filip K

AU - Christensen, Mikkel B

AU - Holst, Jens J

N1 - © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2019/10/26

Y1 - 2019/10/26

N2 - BACKGROUND: Glucose-dependent insulinotropic polypeptide(GIP) has been suggested to stimulate the secretion of pancreatic polypeptide(PP), an islet hormone thought to regulate gut motility, appetite and glycemia.OBJECTIVE: To determine whether human GIP1-42 (hGIP) stimulates PP secretion.METHOD: As glycemia modulates the secretion of PP, we measured plasma PP concentrations from two studies in healthy men(n=10) and in patients with type 2 diabetes (T2D)(n=12), where hGIP1-42 had been administered intravenously during fasting glycemia, hyperglycemia(12mmol/L) and insulin-induced hypoglycemia (targets: 2.5mmol/L(healthy)/3.5mmol/L(T2D)). Porcine GIP1-42 (pGIP) was also infused intra-arterially in isolated porcine pancreata(n=4).RESULTS: Mean fasting plasma glucose concentrations were ~5mmol/L(healthy) and ~8mmol/L(T2D).At fasting glycemia, PP concentrations were higher during intravenous hGIP1-42 infusion compared with saline in healthy men (mean(SEM), net iAUCs0;30min 403(116) vs. -6(57) pmol/L×min,p=0.004) and in patients with T2D (905(177) vs. -96(86)pmol/L×min,p=0.009). During hyperglycemic clamping, PP concentrations were significantly higher during hGIP1-42 infusion compared with saline in patients with T2D (771(160) vs. -183(117)pmol/L×min,p=0.001), but not in healthy individuals (-8(86) vs. -57(53)pmol/L×min,p=0.69). When PG levels were declining in response to exogenous insulin, PP concentrations were higher during hGIP1-42 infusion compared with saline in healthy individuals (294(88) vs. -82(53)pmol/L×min,p=0.0025), but not significantly higher in patients with T2D(586(314) vs. -120(53),p=0.070). At target hypoglycemia , PP levels surged in both groups during both hGIP1-42 and saline infusions.In isolated pancreata, pGIP1-42 increased PP output in the pancreatic venous effluent (baseline vs. infusion, 24(5) vs. 79(16)pmol/min x min,p=0.044).CONCLUSION: GIP1-42 increases plasma PP secretion in healthy individuals, patients with T2D and isolated porcine pancreata. Hyperglycemia blunts the stimulatory effect of hGIP1-42 in healthy individuals, but not in patients with T2D.

AB - BACKGROUND: Glucose-dependent insulinotropic polypeptide(GIP) has been suggested to stimulate the secretion of pancreatic polypeptide(PP), an islet hormone thought to regulate gut motility, appetite and glycemia.OBJECTIVE: To determine whether human GIP1-42 (hGIP) stimulates PP secretion.METHOD: As glycemia modulates the secretion of PP, we measured plasma PP concentrations from two studies in healthy men(n=10) and in patients with type 2 diabetes (T2D)(n=12), where hGIP1-42 had been administered intravenously during fasting glycemia, hyperglycemia(12mmol/L) and insulin-induced hypoglycemia (targets: 2.5mmol/L(healthy)/3.5mmol/L(T2D)). Porcine GIP1-42 (pGIP) was also infused intra-arterially in isolated porcine pancreata(n=4).RESULTS: Mean fasting plasma glucose concentrations were ~5mmol/L(healthy) and ~8mmol/L(T2D).At fasting glycemia, PP concentrations were higher during intravenous hGIP1-42 infusion compared with saline in healthy men (mean(SEM), net iAUCs0;30min 403(116) vs. -6(57) pmol/L×min,p=0.004) and in patients with T2D (905(177) vs. -96(86)pmol/L×min,p=0.009). During hyperglycemic clamping, PP concentrations were significantly higher during hGIP1-42 infusion compared with saline in patients with T2D (771(160) vs. -183(117)pmol/L×min,p=0.001), but not in healthy individuals (-8(86) vs. -57(53)pmol/L×min,p=0.69). When PG levels were declining in response to exogenous insulin, PP concentrations were higher during hGIP1-42 infusion compared with saline in healthy individuals (294(88) vs. -82(53)pmol/L×min,p=0.0025), but not significantly higher in patients with T2D(586(314) vs. -120(53),p=0.070). At target hypoglycemia , PP levels surged in both groups during both hGIP1-42 and saline infusions.In isolated pancreata, pGIP1-42 increased PP output in the pancreatic venous effluent (baseline vs. infusion, 24(5) vs. 79(16)pmol/min x min,p=0.044).CONCLUSION: GIP1-42 increases plasma PP secretion in healthy individuals, patients with T2D and isolated porcine pancreata. Hyperglycemia blunts the stimulatory effect of hGIP1-42 in healthy individuals, but not in patients with T2D.

U2 - 10.1210/clinem/dgz097

DO - 10.1210/clinem/dgz097

M3 - Journal article

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

ER -

ID: 58246605