Distribution and density of melatonin receptors in human main pancreatic islet cell types

Recent investigations of our group established that melatonin modulates hormone secretion of pancreatic islets via melatonin receptor types MT 1 and MT 2. Expression of MT 1 and MT 2 has been shown in mouse, rat, and human pancreatic islets as well as in the β‐, α‐, and δ‐cell lines INS ‐1, α TC 1.9, and QGP ‐1. In view of these earlier investigations, this study was performed to analyze in detail the distribution and density of melatonin receptors on the main islet cell types in human pancreatic tissue obtained from nondiabetic and type 2 diabetic patients. Immunohistochemical analysis established the presence of MT 1 and MT 2 in β‐, α‐, and δ‐cells, but notably, with differences in receptor density. In general, the lowest MT 1 and MT 2 receptor density was measured in α‐cells compared to the 2 other cell types. In type 2 diabetic islets, MT 1 and MT 2 receptor density was increased in δ‐cells compared to normoglycemic controls. In human islets in batch culture of a nondiabetic donor, an increase of somatostatin secretion was observed under melatonin treatment while in islets of a type 2 diabetic donor, an inhibitory influence could be observed, especially in the presence of 5.5 mmol/L glucose. These data suggest the following: i) cell‐type‐specific density of MT 1 and MT 2 receptors in human pancreatic islets, which should be considered in context of the hormone secretion of islets, ii) the influence of diabetes on density of MT 1 and MT 2 as well as iii) the differential impact of melatonin on somatostatin secretion of nondiabetic and type 2 diabetic islets.