TY - JOUR

T1 - The Role of Glucagon in the Pathophysiology and Treatment of Type 2 Diabetes

AU - Hædersdal, Sofie

AU - Lund, Asger

AU - Knop, Filip K

AU - Vilsbøll, Tina

N1 - Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

PY - 2018

Y1 - 2018

N2 - Type 2 diabetes is a disease involving both inadequate insulin levels and increased glucagon levels. While glucagon and insulin work together to achieve optimal plasma glucose concentrations in healthy individuals, the usual regulatory balance between these 2 critical pancreatic hormones is awry in patients with diabetes. Although clinical discussion often focuses on the role of insulin, glucagon is equally important in understanding type 2 diabetes. Furthermore, an awareness of the role of glucagon is essential to appreciate differences in the mechanisms of action of various classes of glucose-lowering therapies. Newer drug classes such as dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists improve glycemic control, in part, by affecting glucagon levels. This review provides an overview of the effect of glucose-lowering therapies on glucagon on the basis of an extensive PubMed literature search to identify clinical studies of glucose-lowering therapies in type 2 diabetes that included assessment of glucagon. Clinical practice currently benefits from available therapies that impact the glucagon regulatory pathway. As clinicians look to the future, improved treatment strategies are likely to emerge that will either use currently available therapies whose mechanisms of action complement each other or take advantage of new therapies based on an improved understanding of glucagon pathophysiology.

AB - Type 2 diabetes is a disease involving both inadequate insulin levels and increased glucagon levels. While glucagon and insulin work together to achieve optimal plasma glucose concentrations in healthy individuals, the usual regulatory balance between these 2 critical pancreatic hormones is awry in patients with diabetes. Although clinical discussion often focuses on the role of insulin, glucagon is equally important in understanding type 2 diabetes. Furthermore, an awareness of the role of glucagon is essential to appreciate differences in the mechanisms of action of various classes of glucose-lowering therapies. Newer drug classes such as dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists improve glycemic control, in part, by affecting glucagon levels. This review provides an overview of the effect of glucose-lowering therapies on glucagon on the basis of an extensive PubMed literature search to identify clinical studies of glucose-lowering therapies in type 2 diabetes that included assessment of glucagon. Clinical practice currently benefits from available therapies that impact the glucagon regulatory pathway. As clinicians look to the future, improved treatment strategies are likely to emerge that will either use currently available therapies whose mechanisms of action complement each other or take advantage of new therapies based on an improved understanding of glucagon pathophysiology.

KW - Diabetes Mellitus, Type 2/metabolism

KW - Glucagon/metabolism

KW - Humans

KW - Hypoglycemic Agents/pharmacology

KW - Insulin/metabolism

U2 - 10.1016/j.mayocp.2017.12.003

DO - 10.1016/j.mayocp.2017.12.003

M3 - Review

C2 - 29307553

VL - 93

SP - 217

EP - 239

JO - Mayo Clinic Proceedings

JF - Mayo Clinic Proceedings

SN - 0025-6196

IS - 2

ER -