The MOR-1 Opioid Receptor Regulates Glucose Homeostasis by Modulating Insulin Secretion
Open Access
- 1 May 2009
- journal article
- other
- Published by The Endocrine Society in Molecular Endocrinology
- Vol. 23 (5), 671-678
- https://doi.org/10.1210/me.2008-0345
Abstract
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 μ-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 β-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.Keywords
This publication has 45 references indexed in Scilit:
- Biphasic insulin secretion from freshly isolated or cultured, perifused rodent islets: comparative studies with rats and miceMetabolism, 2008
- Increased body weight in mice lacking mu-opioid receptorsNeuroReport, 2006
- Antinociceptive and Hypothermic Effects of Salvinorin A Are Abolished in a Novel Strain of κ-Opioid Receptor-1 Knockout MiceThe Journal of pharmacology and experimental therapeutics, 2006
- Oral Antidiabetic AgentsDrugs, 2005
- Opioid Receptor Involvement in Food Deprivation-Induced Feeding: Evaluation of Selective Antagonist and Antisense Oligodeoxynucleotide Probe Effects in Mice and RatsThe Journal of pharmacology and experimental therapeutics, 2004
- Obesity, leptin resistance, and the effects of insulin reductionInternational Journal of Obesity, 2004
- Myostatin Mutation Associated with Gross Muscle Hypertrophy in a ChildThe New England Journal of Medicine, 2004
- Molecular Regulation of AdipogenesisAnnual Review of Cell and Developmental Biology, 2000
- Retention of Supraspinal Delta-like Analgesia and Loss of Morphine Tolerance in δ Opioid Receptor Knockout MiceNeuron, 1999
- A deletion in the bovine myostatin gene causes the double–muscled phenotype in cattleNature Genetics, 1997