INTRODUCTION

Insulin is a peptide hormone composed of 51 amino acids that is synthesized, packaged, and secreted in pancreatic beta cells. The mechanisms of insulin secretion and measurements of beta cell function in normal subjects and patients with various diseases will be reviewed here. The function of the insulin receptor after binding insulin and the mechanisms of insulin action are discussed separately. (See "Structure and function of the insulin receptor" and "Insulin action".)

ANATOMY

Pancreatic beta cells are found in the islets of Langerhans, which are of various size and contain a few hundred to a few thousand endocrine cells. Islets are anatomically and functionally separate from pancreatic exocrine tissue (which secretes pancreatic enzymes and fluid directly into ducts that drain into the duodenum). Normal subjects have about one million islets that in total weigh 1 to 2 grams and constitute 1 to 2 percent of the mass of the pancreas.

Islets vary in size from 50 to 300 micrometers in diameter. They are composed of several types of cells. At least 70 percent are beta cells, which are localized in the core of the islet. These cells are surrounded by alpha cells that secrete glucagon, smaller numbers of delta cells that secrete somatostatin, and PP cells that secrete pancreatic polypeptide (figure 1). All of the cells communicate with each other through extracellular spaces and through gap junctions. This arrangement allows cellular products secreted from one cell type to influence the function of downstream cells. As an example, insulin secreted from beta cells suppresses glucagon secreted from alpha cells.

A neurovascular bundle containing arterioles and sympathetic and parasympathetic nerves enters each islet through the central core of beta cells. The arterioles branch to form capillaries that pass between the cells to the periphery of the islet and then enter the portal venous circulation.

INSULIN SYNTHESIS AND SECRETION

Insulin is synthesized as preproinsulin in the ribosomes of the rough endoplasmic reticulum. Preproinsulin is then cleaved to proinsulin, which is transported to the Golgi apparatus where it is packaged into secretory granules located close to the cell membrane. Proinsulin is cleaved into equimolar amounts of insulin and C-peptide in the secretory granules (figure 2). The process of insulin secretion involves fusion of the secretory granules with the cell membrane and exocytosis of insulin, C-peptide, and proinsulin.