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.
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).
Table 18–1 Islet Cells of the Endocrine Pancreas. |Favorite Table|Download (.pdf)
Table 18–1 Islet Cells of the Endocrine Pancreas.
|Cell Type||Developmental Transcription Factors ||Secretory Products||Islet Composition (%)|
|α||PAX6, MAFB||Glucagon, proglucagon, glucagon-like peptides
|β||PAX6, NKX2.2, NKX6.1, MAFB, PDX1||Insulin, C peptide, proinsulin, amylin, γ-aminobutyric
|PP||Pancreatic polypeptide||(< 1%)|
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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