Insulin and glucagon, the two key hormones that orchestrate fuel storage and use, are produced by the islet cells in the pancreas. Islet cells are distributed in clusters throughout the exocrine pancreas. Together, they comprise the endocrine pancreas. Diabetes mellitus, a heterogeneous disorder, is the most common disease of the endocrine pancreas. Affecting 9% of the world’s adult population in 2014, the prevalence of diabetes continues to increase worldwide, having already more than doubled over the past three decades. Pancreatic tumors secreting excessive amounts of specific islet cell hormones are far less common, but their clinical presentations underscore the important regulatory roles of each hormone.
NORMAL STRUCTURE & FUNCTION OF THE PANCREATIC ISLETS
The endocrine pancreas is composed of nests of cells (islets of Langerhans) that are distributed throughout the exocrine pancreas. This anatomic feature allows for their enzymatic isolation from the exocrine pancreas for islet cell transplantation. Although numbering in the millions, the multicellular islets comprise only 1% of the total pancreas. The endocrine pancreas has great reserve capacity; more than 70% of the insulin-secreting β cells must be lost before dysfunction occurs. Each of the four major islet cell types produces a different secretory product. Insulin-secreting β cells are the predominant cell type (60%). The majority of the remaining islet cells, glucagon-secreting α cells (30%) and somatostatin-secreting δ cells (<10%), secrete hormones that counter the effects of insulin. A fourth islet cell type, the pancreatic polypeptide (PP)–secreting cell (<1%), is primarily located in the posterior lobe of the head of the pancreas, an embryologically distinct region receiving a different blood supply.
The islets are much more highly vascularized than the exocrine pancreatic tissues (see Chapter 15), with at least one major arteriole supplying each islet. The majority of islet cells are closely apposed to the vasculature and to islet cells of opposing types, suggesting an important role for endocrine (via the microcirculation) and/or intra-islet paracrine (via the interstitium) effects on hormone release (Figure 18–1). Blood from the islets then drains into the hepatic portal vein. Thus, the islet cell hormones pass directly into the liver, a major site of action of glucagon and insulin, before proceeding into the systemic circulation, allowing for much higher hepatic than systemic levels of pancreatic hormones.
Schematic diagram indicating paracrine/endocrine regulation of islet cell hormones. Inhibition is indicated by a blunt line, stimulation by an arrow.
The islets are also abundantly innervated. Both parasympathetic and sympathetic axons enter the islets and either directly contact cells or terminate in the interstitial space between the cells. Neural regulation of islet cell hormone release, both directly through the sympathetic fibers and indirectly through the stimulation of catecholamine release by the adrenal medulla, plays a key role in glucose homeostasis during stress.