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The Glucagon-Like Peptides

Departments of Medicine and Physiology (T.J.K.), University of Alberta, Edmonton, Alberta, Canada T6G 2S2; and Laboratory of Molecular Endocrinology (J.F.H.), Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02114

I. Introduction

II. History of the Incretin Concept: Discovery of Gastric Inhibitory Polypeptide

III. Discovery of GLP-1

IV. Structures of GLPs and Family of Glucagon-Related Peptides

V. Tissue Distribution of the Expression of GLPs

A. Pancreatic -cells

B. Intestinal L cells

C. Central nervous system

VI. Proglucagon Biosynthesis

A. Organization/structure of the proglucagon gene

B. Regulation of glucagon gene expression

C. Posttranslational processing of proglucagon

VII. Regulation of GLP Secretion

A. Overview

B. Intracellular signals

C. Carbohydrates

D. Fats

E. Proteins

F. Endocrine

G. Neural

H. GLP-2

VIII. Metabolism of GLPs

A. GLP-1

B. GLP-2

IX. Physiological Actions of GLPs

A. Overview

B. Pancreatic islets

C. Counterregulatory actions of GLP-1 and leptin on ß-cells

D. Stomach

E. Lung

F. Brain

G. Liver, skeletal muscle, and fat

H. Pituitary, hypothalamus, and thyroid

I. Cardiovascular system

J. GLP-2

X. GLP Receptors

A. Structure

B. Signaling

C. Distribution

D. Regulation

E. GLP-2

XI. Pathophysiology of GLP-1

XII. GLP-1 as a Potential Treatment for Diabetes Mellitus

XIII. Future Directions