Endocrine pancreas mechanisms

Nishida, K., Shimoda, S., Ichinose, K., Araki, E., and Shichiri, M. (2009) What is artificial endocrine pancreas Mechanism and history. World Journal of Gastroenterology, 15 (33), 4105-4110. 

Chemistry, mechanism, and effects Glucagon is the product of the A cells of the endocrine pancreas. Like insulin, glucagon is a peptide but unlike insulin, glucagon acts on G protein-coupled receptors. Activation of glucagon receptors, which are located in heart, smooth muscle, and liver, stimulates adenylyl cyclase and increases intracellular cAMP. This results in increases in the heart rate and the force of contraction, increased hepatic glycogenolysis and gluconeogenesis and relaxation of smooth muscle. The smooth muscle effect is particularly marked in the gut. 

Gomez-Acebo, J., Parrilla, R., and Candela, L. R., 1968, Fine structure of the A and D cells of the rabbit endocrine pancreas in vivo and incubated in vitro. I. Mechanism of secretion of the A cells, J. Cell. Biol. 36 33. 

Insulin, which is formed in the B cells of the pancreas, has both endocrine and paracrine effects. As a hormone with endocrine effects, it regulates glucose and fat metabolism. Via a paracrine mechanism, it inhibits the synthesis and release of glucagon from the neighboring A cells. 

Gastric acid secretion can be inhibited by several mechanisms including acid in the stomach (pH 3 inhibits gastrin release), acid in the duodenum, the presence of fat in the pancreas, and hypertonic fluids or hyperglycemia. Somatostatin, a hormone produced by antral mucosal endocrine cells (D cells), inhibits the release of gastrin by directly inhibiting the parietal cells. Somatostatin is also present in other GI tissue and the pancreas. C cells, endocrine cells in the proximal small intestine, secrete secretin in response to mucosal acidification, which also decreases gastric secretion. 

To further characterize the toxicity and investigate its possible mechanism, a 14-day time-course study in the rat was conducted to allow for the observation of the lesion development and progression (Brenneman et al., 2014). Light microscopic (i.e., histochemical and IHC with quantification) and ultrastructural (i.e., TEM) examination showed that the injury appeared to originate as degeneration and loss of endothelial cells in the capillaries at the exocrine-endocrine interface. This injury was not associated with any increases in traditional or exploratory serum biomarkers of exocrine injury nor any evidence of endocrine dysfunction as assessed via an OGTT however, it was associated with an increase in EMPs that was not pancreas specific. 

Significance and Mode of Action.— Langdon Brown has suggested that the animal autacoids are the survival of the primitive chemical apparatus which regulated the organism before the evolution of a central nervous system, which, when it arose, became allied to the pre-existing endocrine system in two ways. The sympathetic mechanism became associated with the adrenal, thyroid and pituitary glands the parasympathetic mechanism became associated with the insular tissue of the pancreas and with the choline bases. 

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