The islet ghrelin cell

Abstract

The islets of Langerhans are key regulators of glucose homeostasis and have been known as a structure for almost one and a half centuries. During the twentieth century several different cell types were described in the islets of different species and at different developmental stages. Six cell types with identified hormonal product have been described so far by the use of histochemical staining methods, transmission electron microscopy, and immunohistochemistry. Thus, glucagon-producing a-cells, insulin-producing b-cells, somatostatin-producing d-cells, pancreatic polypeptide-producing PP-cells, serotoninproducing enterochromaffin-cells, and gastrin-producing G-cells have all been found in the mammalian pancreas at least at some developmental stage. Species differences are at hand and age-related differences are also to be considered. Eleven years ago a novel cell type, the ghrelin cell, was discovered in the human islets. Subsequent studies have shown the presence of islet ghrelin cells in several animals, including mouse, rat, gerbils, and fish. The developmental regulation of ghrelin cells in the islets of mice has gained a lot of interest and several studies have added important pieces to the puzzle of molecular mechanisms and the genetic regulation that lead to differentiation into mature ghrelin cells. A body of evidence has shown that ghrelin is an insulinostatic hormone, and the potential for blockade of ghrelin signalling as a therapeutic avenue for type 2 diabetes is intriguing. Furthermore, ghrelin-expressing pancreatic tumours have been reported and ghrelin needs to be taken into account when diagnosing pancreatic tumours. In this review article, we summarise the knowledge about islet ghrelin cells obtained so far.

β1-Adrenergic receptor deficiency in ghrelin-expressing cells causes hypoglycemia in susceptible individuals

“…40-44]) and a majority (~69%) of the highly dispersed, far less numerous population of ghrelin cells in the duodenum (35). Other cells with Cre activity include Leydig cells of the testis, epithelial cells of the epididymis, and scarce cells within some pancreatic islets, all of which correspond to known ghrelin cell distribution patterns (44)(45)(46)(47)(48)(49). Germline transmission of the recombinant loxP-flanked Adrb1 gene was validated by PCR analysis of genomic DNA obtained by tail snips (Supplemental Figure 3, A ).…”

Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes

“…Ghrelin is released not only by P/D1 cells from the stomach but also by 3-cells from the pancreas (Wierup et al 2013). Only few 3-cells are present in each islet.…”

“…Only few 3-cells are present in each islet. Ghrelin inhibits insulin and somatostatin secretion, but increases glucagon release (Chuang et al 2011, Wierup et al 2013. In addition, this hormone potently stimulates growth hormone release from the anterior pituitary gland and stimulates appetite (Malik et al 2008).…”

Nutrient regulation of insulin secretion and action

“…Furthermore, T2DM is by far the most common form of the disease, representing about 90-95% of DM cases. Pancreatic islets are specialised and highly vascularised structures that monitor the nutrient contents of the blood stream and consist of mainly five cell types; a-cells, b-cells, d-cells, ghrelin cells (g-cells) and pancreatic peptide (PP)-secreting cells (Wierup et al 2014). Islets continually sample blood from the branches of the splenic and pancreaticoduodenal arteries (Gray's Anatomy 1995) and react to elevated dietary nutrients by directly secreting insulin from b-cells into the blood stream or glucagon from a-cells (in response to nutrient-deprived states such as fasting and starvation).…”

“…Islets continually sample blood from the branches of the splenic and pancreaticoduodenal arteries (Gray's Anatomy 1995) and react to elevated dietary nutrients by directly secreting insulin from b-cells into the blood stream or glucagon from a-cells (in response to nutrient-deprived states such as fasting and starvation). Interestingly, b-cells are the most studied cell of the islet and account for w50% of the islet cell mass in humans, while a-cells comprise about 35-40%, with the remainder made up of somatostatinsecreting d-cells, g-cells and PP-cells that play a regulatory function (Cabrera et al 2006, Rorsman & Braun 2013, Wierup et al 2014. As b-cells are responsible for the biosynthesis and distribution of insulin into the blood stream, they have an important clinical impact.…”