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198-OR: The Stimulatory Effect of Glucagon on Insulin Secretion Is Glucose Dependent in Healthy Human Subjects

Publication ,  Conference
GRAY, SM; ZHANG, G-F; BENNETT, W; TONG, J; CAMPBELL, J; D’ALESSIO, DA
Published in: Diabetes
June 1, 2021

Glucagon is generally considered to be a counter-regulatory hormone with a primary role to raise blood glucose concentrations by increasing endogenous glucose production (EGP). However, recent preclinical findings support a paracrine action of glucagon to act directly on pancreatic beta cells to promote nutrient-stimulated insulin secretion. In mice, the divergent actions of glucagon are dependent on glycemic status: during fasting glucagon acts predominantly at the liver to raise blood glucose, whereas in the fed state when glycemia is elevated, the insulinotropic effects predominate to lower glucose. These mechanistic findings have not been extended to human physiology. Therefore, we designed a study to test the hypothesis that in healthy humans glucagon actions are also dependent on ambient glycemia. Subjects received glucagon (100 ng/kg) during fasting euglyemia or experimental hyperglycemia (~150 mg/dl) on separate days. On both days, glycemia was maintained for 60 min prior to a glucagon infusion for an additional 60 min. Blood glucose was monitored at bedside and plasma samples were analyzed for C-peptide and di-deuterated glucose enrichment to calculate HGP. During fasting euglycemia, blood glucose was 85 mg/dl and glucagon elicited an increase to a 60 minute average of 132 mg/dl with a peak at ~156 mg/dl at the end of the infusion. Concordant with increased glycemia was an immediate increase in HGP (1.8x) and a delayed increase in C-peptide AUC (1.5x). For the hyperglycemia studies, blood glucose was maintained at 150 mg/dl before and during glucagon administration. Here, glucagon caused a rapid and robust increase in C-peptide AUC (4x) and a more gradual increase in HGP (2x). This glycemic-dependent behavior of glucagon suggests a physiologic role to promote prandial insulin secretion in healthy subjects. This raises the possibility that this incretin function of glucagon plays a role in β-cell function in diabetic subjects.

Duke Scholars

Published In

Diabetes

DOI

EISSN

1939-327X

ISSN

0012-1797

Publication Date

June 1, 2021

Volume

70

Issue

Supplement_1

Publisher

American Diabetes Association

Related Subject Headings

  • Endocrinology & Metabolism
  • 32 Biomedical and clinical sciences
  • 11 Medical and Health Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
GRAY, S. M., ZHANG, G.-F., BENNETT, W., TONG, J., CAMPBELL, J., & D’ALESSIO, D. A. (2021). 198-OR: The Stimulatory Effect of Glucagon on Insulin Secretion Is Glucose Dependent in Healthy Human Subjects. In Diabetes (Vol. 70). American Diabetes Association. https://doi.org/10.2337/db21-198-or
GRAY, SARAH M., G. U. O. -. F. A. N. G. ZHANG, W. I. L. L. I. A. M. BENNETT, J. E. N. N. Y. TONG, J. O. N. A. T. H. A. N. CAMPBELL, and DAVID A. D’ALESSIO. “198-OR: The Stimulatory Effect of Glucagon on Insulin Secretion Is Glucose Dependent in Healthy Human Subjects.” In Diabetes, Vol. 70. American Diabetes Association, 2021. https://doi.org/10.2337/db21-198-or.
GRAY SM, ZHANG G-F, BENNETT W, TONG J, CAMPBELL J, D’ALESSIO DA. 198-OR: The Stimulatory Effect of Glucagon on Insulin Secretion Is Glucose Dependent in Healthy Human Subjects. In: Diabetes. American Diabetes Association; 2021.
GRAY, SARAH M., et al. “198-OR: The Stimulatory Effect of Glucagon on Insulin Secretion Is Glucose Dependent in Healthy Human Subjects.” Diabetes, vol. 70, no. Supplement_1, American Diabetes Association, 2021. Crossref, doi:10.2337/db21-198-or.
GRAY SM, ZHANG G-F, BENNETT W, TONG J, CAMPBELL J, D’ALESSIO DA. 198-OR: The Stimulatory Effect of Glucagon on Insulin Secretion Is Glucose Dependent in Healthy Human Subjects. Diabetes. American Diabetes Association; 2021.

Published In

Diabetes

DOI

EISSN

1939-327X

ISSN

0012-1797

Publication Date

June 1, 2021

Volume

70

Issue

Supplement_1

Publisher

American Diabetes Association

Related Subject Headings

  • Endocrinology & Metabolism
  • 32 Biomedical and clinical sciences
  • 11 Medical and Health Sciences