Immunoneutralization of Somatostatin, Insulin, and Glucagon Causes Alterations in Islet Cell Secretion in the Isolated Perfused Human Pancreas

Abstract

The variation in hormonal responses to immunoneutralization during stimulated and nonstimulated glucose conditions suggests that a dynamic association exists between the pancreatic cells.

Function and expression of somatostatin receptors of the endocrine pancreas

“…It has been postulated that the postabsorptive increase of SST secretion may provide a mechanism to prevent excessive glucagon secretion (D'Alessio et al, 1989;Klaff and Taborsky, Jr. 1987). However, the role of pancreatic SST in inhibiting glucagon secretion may be more relevant in the basal state, because anti-SST enhanced glucagon output from the perfused human pancreas only at low glucose concentrations (Brunicardi et al, 2001;Kleinman et al, 1994). The physiological relevance of the inhibition of insulin secretion by SST at high glucose could be a prevention of postabsorptive insulin hypersecretion, providing a mechanism to protect against development of postprandial hypoglycemia.…”

“…Among the stimuli of SST secretion from intestinal and pancreatic D-cells, glucose, amino acids such arginine, isoleucine, as well as, ketone bodies, and hormones (CCK, gastrin, secretin) were identified (Hermansen 1980). Insulin stimulates SST secretion at high glucose concentrations, only (Brunicardi et al, 2001). Since SST can directly suppress insulin synthesis and release (see below), it appears that insulin clamps its own secretion by stimulating SST release.…”

Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells

“…Human islets contain about 10% delta cells, which is twice the proportion of mouse islets [1]. Pancreatic somatostatin has no major direct effect on glucose metabolism, but is a potent paracrine inhibitor of both insulin and glucagon secretion [2,3]. Paracrine regulation of insulin and glucagon release is facilitated by the delta cells being distributed throughout the islet in man rather than confined to the islet periphery, as in rodents [4].…”

Extracorporeal perfusion of isolated organs of large animals – Bridging the gap between in vitro and in vivo studies

“…Reported diluents have been cell free solutions (Domingo-Pech et al, 1991;Wagner et al, 2003;Erasmus et al, 2006;Friebe et al, 2013b) or autologous plasma (Patan et al, 2009;Patan-Zugaj et al, 2012, which comes with the added benefit of increasing oncotic pressure. As cell free solutions are associated with low oncotic pressure, resulting in edema formation and weight gain, adding plasma expanders such as plasma proteins (Verbeke et al, 1968;Roets et al, 1974;Patan et al, 2009) and purified albumin (Rehfeld et al, 1982;Barthel et al, 1989;Riviere et al, 1989;Brunicardi et al, 2001) perfused specimens thus reflects the degree of ischemia/reperfusion injury (Petrasek et al, 1994;Adham et al, 1997) and the integrity of the microvasculature (Müller et al, 2013). Excessive edema formation results in rapidly progressive deterioration of organ function, which renders it unsuitable for transplantation and research alike (Verbeke et al, 1972).…”