**7. The cells of the pancreas**

Histologically, the adult pancreas consists of endocrine and exocrine cells, but these cells can change their state of differentiation in response to various stimuli (e.g., injury or stress). The *exocrine* portion of the pancreas produces and releases enzymes that digest proteins and lipids. In contrast, the *endocrine* portion produces hormones such as insulin and glucagon, which control blood glucose levels. During the cephalic phase of digestion, even before food enters the mouth, digestive enzymes and insulin are secreted to regulate and coordinate metabolic processes.

Over millions of years of evolution, large portions of what we today call the pancreas evolved originally from just exocrine tissue. As a result of this evolution, endocrine cells form encapsulated boundaries called islets of Langerhans, that separate the endocrine and exocrine acini within the pancreas [15].

Moreover, many cell types are present within these evolved islets: the alpha (α), beta (β), and delta (δ) cells produce the vital hormones glucagon, insulin, and somatostatin, respectively. A fourth cell type, known as the pancreatic polypeptide (PP)

### **Figure 1.**

*Schematic diagram showing the interaction of islet cells. Evidence points to the transdifferentiation (light blue arrow) of α-cells (red) via stimulation by gamma aminobutyric acid (GABA), and δ-cells (pink) into insulinproducing β-cells (green). It is unknown whether the replacement of β-cells by α-cells is able to take the place of hub β-cells (light blue) which influence the function of other β-cells (yellow arrows). Somatostatin released from δ-cells can inhibit the release of glucagon, insulin, and pancreatic polypeptide from α-, β-, and PP cells (purple), respectively. Pancreatic polypeptide released from PP cells can inhibit the release of glucagon. Ghrelin released from ghrelin-positive islet cells (orange) can inhibit insulin and somatostatin secretion.*

cell has the significant function of inhibiting glucagon release. Yet other cell types, ghrelin-positive cells, are mainly found in the gut and in the islet to inhibit insulin and somatostatin secretion and regulate the secretion of glucagon, PP, and somatostatin (**Figure 1**) [16]. Evidence in the literature, and discussed in detail by Da Silva Xavier [16], suggests transdifferentiation of α-cells via stimulation by gamma-aminobutyric acid and δ-cells into insulin-containing β (like)-cells. It is unknown whether the replenishment of β-cells from the transdifferentiation of α-cells is able to replace hub (stem) β-cells which influence the function of other β-cells (**Figure 1**) [16]. In any case, the pancreas does appear to have some reserve capacity for the regeneration of β-cells but this may be overwhelmed in DM.

In fact, the most abundant cells in the islets of Langerhans are the β-cells, comprising 55% of the cell number, and it has been suggested that they interact with other endocrine cells to influence the secretion of hormones [8]. Moreover, because the β-cells produce insulin they are the most critical pancreatic cell type involved in the etiology DM. It is therefore timely at this point to look at insulin production in more detail.
