In:
PLOS ONE, Public Library of Science (PLoS), Vol. 19, No. 4 ( 2024-4-18), p. e0301496-
Abstract:
Obesity leads to insulin resistance (IR) and type 2 diabetes. In humans, low levels of the hormone prolactin (PRL) correlate with IR, adipose tissue (AT) dysfunction, and increased prevalence of T2D. In obese rats, PRL treatment promotes insulin sensitivity and reduces visceral AT adipocyte hypertrophy. Here, we tested whether elevating PRL levels with the prokinetic and antipsychotic drug sulpiride, an antagonist of dopamine D2 receptors, improves metabolism in high fat diet (HFD)-induced obese male mice. Sulpiride treatment (30 days) reduced hyperglycemia, IR, and the serum and pancreatic levels of triglycerides in obese mice, reduced visceral and subcutaneous AT adipocyte hypertrophy, normalized markers of visceral AT function (PRL receptor, Glut4, insulin receptor and Hif-1α), and increased glycogen stores in skeletal muscle. However, the effects of sulpiride reducing hyperglycemia were also observed in obese prolactin receptor null mice. We conclude that sulpiride reduces obesity-induced hyperglycemia by mechanisms that are independent of prolactin/prolactin receptor activity. These findings support the therapeutic potential of sulpiride against metabolic dysfunction in obesity.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0301496
DOI:
10.1371/journal.pone.0301496.g001
DOI:
10.1371/journal.pone.0301496.g002
DOI:
10.1371/journal.pone.0301496.g003
DOI:
10.1371/journal.pone.0301496.g004
DOI:
10.1371/journal.pone.0301496.g005
DOI:
10.1371/journal.pone.0301496.g006
DOI:
10.1371/journal.pone.0301496.g007
DOI:
10.1371/journal.pone.0301496.s001
DOI:
10.1371/journal.pone.0301496.s002
DOI:
10.1371/journal.pone.0301496.s003
DOI:
10.1371/journal.pone.0301496.s004
DOI:
10.1371/journal.pone.0301496.s005
DOI:
10.1371/journal.pone.0301496.r001
DOI:
10.1371/journal.pone.0301496.r002
DOI:
10.1371/journal.pone.0301496.r003
DOI:
10.1371/journal.pone.0301496.r004
DOI:
10.1371/journal.pone.0301496.r005
DOI:
10.1371/journal.pone.0301496.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2024
detail.hit.zdb_id:
2267670-3
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