TY - JOUR

T1 - Treatment of Type 2 Diabetes and Obesity on the Basis of the Incretin System

T2 - The 2021 Banting Medal for Scientific Achievement Award Lecture

AU - Holst, Jens Juul

N1 - © 2021 by the American Diabetes Association.

PY - 2021

Y1 - 2021

N2 - In my lecture given on the occasion of the 2021 Banting Medal for Scientific Achievement, I briefly described the history of the incretin effect and summarized some of the developments leading to current therapies of obesity and diabetes based on the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). In the text below, I discuss in further detail the role of these two hormones for postprandial insulin secretion in humans on the basis of recent studies with antagonists. Their direct and indirect actions on the β-cells are discussed next as well as their contrasting actions on glucagon secretion. After a brief discussion of their effect on insulin sensitivity, I describe their immediate actions in patients with type 2 diabetes and emphasize the actions of GLP-1 on β-cell glucose sensitivity, followed by a discussion of their extrapancreatic actions, including effects on appetite and food intake in humans. Finally, possible mechanisms of action of GIP-GLP-1 coagonists are discussed, and it is concluded that therapies based on incretin actions are likely to change the current hesitant therapy of both obesity and diabetes.

AB - In my lecture given on the occasion of the 2021 Banting Medal for Scientific Achievement, I briefly described the history of the incretin effect and summarized some of the developments leading to current therapies of obesity and diabetes based on the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). In the text below, I discuss in further detail the role of these two hormones for postprandial insulin secretion in humans on the basis of recent studies with antagonists. Their direct and indirect actions on the β-cells are discussed next as well as their contrasting actions on glucagon secretion. After a brief discussion of their effect on insulin sensitivity, I describe their immediate actions in patients with type 2 diabetes and emphasize the actions of GLP-1 on β-cell glucose sensitivity, followed by a discussion of their extrapancreatic actions, including effects on appetite and food intake in humans. Finally, possible mechanisms of action of GIP-GLP-1 coagonists are discussed, and it is concluded that therapies based on incretin actions are likely to change the current hesitant therapy of both obesity and diabetes.

U2 - 10.2337/dbi21-0026

DO - 10.2337/dbi21-0026

M3 - Journal article

C2 - 34711671

VL - 70

SP - 2468

EP - 2475

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -