The hepatopancreatic complex, along with the gall bladder, is responsible for the integrated digestion and subsequent processing of most dietary nutrients (Figure 1). The pancreas contributes to both the digestive and endocrine systems of vertebrates. It is both an endocrine gland that produces several important hormones, including insulin, glucagon, and somatostatin (see Table1), as well as an exocrine gland, secreting pancreatic digestive enzymes (chymotrypsin and trypsin, amylase and lipase, as well as bicarbonate) that pass to the small intestine. These enzymes help in the further breakdown of the protein, carbohydrates, and fat in the chyme.
Fig1. Gross anatomical features of a human pancreas, liver, biliary system, intestinal duodenum, and stomach.
Table1. Hormones Secreted by the Pancreas
Anatomically, the pancreas has distinct dorsal (rear side) and ventral (front side) lobes. The pancreas can be divided into lobules that (a) contain the exocrine acinar glands that contain pancreatic digestive enzymes and (b) the endocrine islets of Langerhans that contain insulin, glucagon, and somatostatin for secretion. The endocrine protein of the pancreas constitutes only 1–2% of the weight of the gland.
Figure 2A lists the major biological function(s) of the five hormones secreted by the pancreas. Also shown schematically is the proportion of the human pancreas islet cells dedicated to the secretion of insulin, glucagon, somatostatin, and the smaller amounts of pancreatic polypeptide (PP) and gastrin.
Fig2. Schematic diagram of the cell types of a human pancreatic islet. (A) Illustration of the relative proportion of cells that secrete insulin (B cells), glucagon (A cells), somatostatin (D cells), pancreatic polypeptide (PP cells), and gastrin (G cells). The hormones are secreted and taken up into the pancreatic arteriole/capillary/venule system which ultimately delivers them to distal target organs (defined by the presence of their cognate receptor) where biological responses are then generated. The major biological functions of each hormone are listed in the green box.
1. Cells of the Pancreatic Islets
In both humans and rats, pancreatic islets are com posed of at least three major cell types: they are the α or A (glucagon-secreting) cells, the β or B (insulin-secreting) cells, and the δ or D cells (somatostatin secreting cells). By histological staining with neutral red it has been estimated that there are 13,500 or 890,000 islets, respectively, in the rat and human pancreas. The islets in the rat pancreas range in diameter from 50 to 400 μm. The distribution of cells in a typical rat islet is 15–18% α, 75–80% β, and 2–10% δ. The islets are surrounded by a basement membrane that encloses all three cell types (see Figure 2B).
The pancreatic β-cell also produces a neuropeptide like molecule known as amylin or islet amyloid poly peptide (IAPP). Amylin is a 37 amino acid peptide with a sequence homology to calcitonin (see Chapter 9). It is cosecreted with insulin in a ratio of 1 amylin to 100 insulin molecules. It was first described as a major protein component of the amyloid deposits that are found in the islets of elderly type I diabetics. The physiological function of amylin is believed to be linked to satiety, which is the quality or state of being fed or gratified beyond capacity.
The pancreas of humans and 13 other species also secretes pancreatic polypeptide (PP). The physiologic function of PP is to stimulate the secretion of gastric acid (HCl) by parietal cells of the stomach.
2. Vascularization and Innervation of Pancreatic Islets
The arterial supply of the pancreas arises from the splenic, hepatic, and mesenteric arteries, and venous drainage is into the splenic and mesenteric veins. Each islet is normally vascularized by 1–3 arterioles, which abruptly terminate into capillaries, and 1–6 venules, depending upon the size of the islet (see Figure 2B). Morphological studies of the islets indicate that their endocrine cells are arranged so that each islet cell is adjacent to a capillary. This permits the rapid trans fer of the secreted hormones into the general vascular system.
The capillaries present in the pancreatic islets comprise endothelial cells that are fenestrated to permit the rapid uptake of the peptide hormones. The hormonal products secreted by islet cells into the surrounding extracellular fluid must traverse the basement membrane of the endothelium before entering the bloodstream.
Both adrenergic and cholinergic nerve fibers are present in both the acinar and the islet regions of the pancreas. Stimulation of the parasympathetic nervous system leads to insulin secretion and inhibition of glucagon secretion, irrespective of whether the stimuli occur at the lateral hypothalamic nuclei, the motor nuclei of the vagus, or the mixed pancreatic nerves. Stimulation of the sympathetic nervous system or application of epinephrine likewise can stimulate glucagon production and inhibit insulin secretion. The hypothalamus appears to play the major integrating role in the balance between sympathetic and parasympathetic regulation of the islet.
