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Insulin and glucagon, the two key hormones that orchestrate fuel storage and utilization, 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 that affects 8% of the population in the United States and more than 20% of individuals between the ages of 65 and 74 years, is the most common disease associated with disordered secretion of hormones of the endocrine pancreas. Pancreatic tumors that secrete excessive amounts of specific islet cell hormones are far less common, but their clinical presentations underscore the important regulatory roles of each hormone.

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Anatomy & Histology

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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 (Table 18–1). Insulin-secreting β cells are the predominant cell type. The majority of the remaining islet cells, glucagon-secreting α cells and somatostatin-secreting δ cells, secrete hormones that counter the effects of insulin. A fourth major islet cell type, the pancreatic polypeptide-secreting PP cell, is primarily located in islets within the posterior lobe of the head of the pancreas, an embryologically distinct region receiving a different blood supply. Current limitations associated with islet cell transplantation have stimulated interest in the potential use of stem cell–derived islet cells and, with this, a renewed interest in elucidating transcription factors critical for the differentiation of specific endocrine (vs. exocrine) pancreatic cells from a single progenitor (Table 18–1).

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Table Graphic Jump Location
Table 18–1 Islet Cells of the Endocrine Pancreas.
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The islets are much more highly vascularized than the exocrine pancreatic tissues. At least one major arteriole supplies each islet and is lined with islet cells whose secretory products exert intraislet, paracrine, or endocrine effects on hormone release (Figure 18–1). Blood from the islets then drains into the hepatic portal vein. Thus, the islet cell secretory products pass directly into the liver, a major site of action of glucagon and insulin, before proceeding into the systemic circulation.

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