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Mol Endocrinol. 2009 May;23(5):671-8. doi: 10.1210/me.2008-0345. Epub 2009 Feb 12.

The MOR-1 opioid receptor regulates glucose homeostasis by modulating insulin secretion.

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Department of Cell Biology and Neuroscience, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.


In addition to producing analgesia, opioids have also been proposed to regulate glucose homeostasis by altering insulin secretion. A considerable controversy exists, however, regarding the contribution of the mu-opioid receptor (MOR-1) to insulin secretion dynamics. We employed congenic C57BL/6J MOR-1 knockout (KO) mice to clarify the role of MOR in glucose homeostasis. We first found that both sexes of MOR-1 KO mice weigh more than wild-type mice throughout postnatal life and that this increase includes preferentially increased fat deposition. We also found that MOR-1 KO mice exhibit enhanced glucose tolerance that results from insulin hypersecretion that reflects increased beta-cell mass and increased secretory dynamics in the MOR-1 mutant mice compared with wild type. Analysis of the isolated islets indicated that islet insulin hypersecretion is mediated directly by MOR expressed on islet cells via a mechanism downstream of ATP-sensitive K(+) channel activation by glucose. These findings indicate that MOR-1 regulates body weight by a mechanism that involves insulin secretion and thus may represent a novel target for new diabetes therapies.

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