The MOR-1 opioid receptor regulates glucose homeostasis by modulating insulin secretion.
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.
Wen
Ting
T
Department of Cell Biology and Neuroscience, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
Peng
Bonnie
B
Pintar
John E
JE
D000818:Animals; D001823:Body Composition / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000235:genetics; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007328:Insulin; D017450:Receptors, Opioid, mu; D005947:Glucose