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Metabolism

Glucose-Dependent Insulinotropic Polypeptide

A Bifunctional Glucose-Dependent Regulator of Glucagon and Insulin Secretion in Humans

  1. Mikkel Christensen1,2⇓,
  2. Louise Vedtofte1,
  3. Jens J. Holst2,
  4. Tina Vilsbøll1 and
  5. Filip K. Knop1
  1. 1Diabetes Research Division, Department of Internal Medicine F, Gentofte Hospital, Copenhagen, Denmark
  2. 2Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark
  1. Corresponding author: Mikkel Christensen, mch{at}dadlnet.dk.
Diabetes 2011 Dec; 60(12): 3103-3109. https://doi.org/10.2337/db11-0979
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Abstract

OBJECTIVE To evaluate the glucose dependency of glucose-dependent insulinotropic polypeptide (GIP) effects on insulin and glucagon release in 10 healthy male subjects ([means ± SEM] aged 23 ± 1 years, BMI 23 ± 1 kg/m2, and HbA1c 5.5 ± 0.1%).

RESEARCH DESIGN AND METHODS Saline or physiological doses of GIP were administered intravenously (randomized and double blinded) during 90 min of insulin-induced hypoglycemia, euglycemia, or hyperglycemia.

RESULTS During hypoglycemia, GIP infusion caused greater glucagon responses during the first 30 min compared with saline (76 ± 17 vs. 28 ± 16 pmol/L per 30 min, P < 0.008), with similar peak levels of glucagon reached after 60 min. During euglycemia, GIP infusion elicited larger glucagon responses (62 ± 18 vs. −11 ± 8 pmol/L per 90 min, P < 0.005). During hyperglycemia, comparable suppression of plasma glucagon (−461 ± 81 vs. −371 ± 50 pmol/L per 90 min, P = 0.26) was observed with GIP and saline infusions. In addition, during hyperglycemia, GIP more than doubled the insulin secretion rate (P < 0.0001).

CONCLUSIONS In healthy subjects, GIP has no effect on glucagon responses during hyperglycemia while strongly potentiating insulin secretion. In contrast, GIP increases glucagon levels during fasting and hypoglycemic conditions, where it has little or no effect on insulin secretion. Thus, GIP seems to be a physiological bifunctional blood glucose stabilizer with diverging glucose-dependent effects on the two main pancreatic glucoregulatory hormones.

  • Received July 14, 2011.
  • Accepted September 2, 2011.
  • © 2011 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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Diabetes: 60 (12)

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December 2011, 60(12)
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Glucose-Dependent Insulinotropic Polypeptide
Mikkel Christensen, Louise Vedtofte, Jens J. Holst, Tina Vilsbøll, Filip K. Knop
Diabetes Dec 2011, 60 (12) 3103-3109; DOI: 10.2337/db11-0979

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Glucose-Dependent Insulinotropic Polypeptide
Mikkel Christensen, Louise Vedtofte, Jens J. Holst, Tina Vilsbøll, Filip K. Knop
Diabetes Dec 2011, 60 (12) 3103-3109; DOI: 10.2337/db11-0979
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