Home LiteratureArticle Details
PMID: 11581309 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Central melanocortin receptors regulate insulin action.

The Journal of clinical investigation ·Vol. 108 ·No. 7 ·2001-10-00 ·Pages 1079-85

Obici S, Feng Z, Tan J, Liu L, Karkanias G, Rossetti L

Abstract

Energy balance and insulin action are tightly coregulated. Leptin regulates energy intake and expenditure partly by modulation of the melanocortin pathway in the hypothalamus. Here we demonstrate potent effects of the melanocortin pathway on insulin action and body distribution of adiposity. Conscious rats received week-long infusions of either a melanocortin receptor agonist, alpha-melanocyte-stimulating hormone (alpha-MSH), or antagonist, SHU9119, in the third cerebral ventricle while food intake was maintained constant in each group. alpha-MSH decreased intra-abdominal fat and markedly enhanced the actions of insulin on both glucose uptake and production, while SHU9119 exerted opposite effects. Our findings elucidate a neuroendocrine network that is likely to play a central role in the coupling of energy intake and insulin action.

MeSH Terms
Animals Glucose/metabolism Hypothalamus/metabolism Insulin/metabolism Insulin Receptor Substrate Proteins Intracellular Signaling Peptides and Proteins Male Melanocyte-Stimulating Hormones/adverse effects,pharmacology Oligodeoxyribonucleotides, Antisense Phosphoproteins/metabolism Phosphorylation Rats Rats, Sprague-Dawley Receptor, Melanocortin, Type 3 Receptor, Melanocortin, Type 4 Receptors, Corticotropin/agonists,antagonists & inhibitors,metabolism Receptors, Peptide/agonists,antagonists & inhibitors,genetics,metabolism Signal Transduction alpha-MSH/adverse effects,pharmacology
Chemicals
Insulin Insulin Receptor Substrate Proteins Intracellular Signaling Peptides and Proteins Irs1 protein, rat Irs2 protein, rat Oligodeoxyribonucleotides, Antisense Phosphoproteins Receptor, Melanocortin, Type 3 Receptor, Melanocortin, Type 4 Receptors, Corticotropin Receptors, Peptide SHU 9119 alpha-MSH Melanocyte-Stimulating Hormones Glucose
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Obici S
Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York, USA 10461.
Feng Z
Tan J
Liu L
Karkanias G
Rossetti L
References (32)
32 references, click to expand
  1. Stability, clearance, and disposition of intraventricularly administered oligodeoxynucleotides: implications for therapeutic application within the central nervous system.
    Proc Natl Acad Sci U S A. 1993 May 15;90(10):4665-9 PMID: 8506315
  2. What if Minkowski had been ageusic? An alternative angle on diabetes.
    Science. 1992 Oct 30;258(5083):766-70 PMID: 1439783
  3. Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur.
    Proc Natl Acad Sci U S A. 1995 May 23;92(11):4728-32 PMID: 7761391
  4. Effects of the obese gene product on body weight regulation in ob/ob mice.
    Science. 1995 Jul 28;269(5223):540-3 PMID: 7624776
  5. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks.
    Science. 1995 Jul 28;269(5223):546-9 PMID: 7624778
  6. Recombinant ob protein reduces feeding and body weight in the ob/ob mouse.
    J Clin Invest. 1995 Oct;96(4):2065-70 PMID: 7560100
  7. Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice.
    Diabetes. 1996 Apr;45(4):531-5 PMID: 8603777
  8. Identification of targets of leptin action in rat hypothalamus.
    J Clin Invest. 1996 Sep 1;98(5):1101-6 PMID: 8787671
  9. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome.
    Nature. 1997 Jan 9;385(6612):165-8 PMID: 8990120
  10. Targeted disruption of the melanocortin-4 receptor results in obesity in mice.
    Cell. 1997 Jan 10;88(1):131-41 PMID: 9019399
  11. Effects of leptin on insulin sensitivity in normal rats.
    Endocrinology. 1997 Aug;138(8):3395-401 PMID: 9231793
  12. Acute stimulation of glucose metabolism in mice by leptin treatment.
    Nature. 1997 Sep 25;389(6649):374-7 PMID: 9311777
  13. Short term effects of leptin on hepatic gluconeogenesis and in vivo insulin action.
    J Biol Chem. 1997 Oct 31;272(44):27758-63 PMID: 9346919
  14. Inhibition of food response to intracerebroventricular injection of leptin is attenuated in rats with diet-induced obesity.
    Diabetes. 1997 Nov;46(11):1782-5 PMID: 9356026
  15. Independent and additive effects of central POMC and leptin pathways on murine obesity.
    Science. 1997 Nov 28;278(5343):1641-4 PMID: 9374468
  16. Leptin activates PI-3 kinase in C2C12 myotubes via janus kinase-2 (JAK-2) and insulin receptor substrate-2 (IRS-2) dependent pathways.
    Diabetologia. 1997 Nov;40(11):1358-62 PMID: 9389430
  17. Melanocortin receptors in leptin effects.
    Nature. 1997 Nov 27;390(6658):349 PMID: 9389472
  18. Leptin selectively decreases visceral adiposity and enhances insulin action.
    J Clin Invest. 1997 Dec 15;100(12):3105-10 PMID: 9399957
  19. 13C/31P NMR studies on the mechanism of insulin resistance in obesity.
    Diabetes. 1998 Mar;47(3):381-6 PMID: 9519743
  20. A nutrient-sensing pathway regulates leptin gene expression in muscle and fat.
    Nature. 1998 Jun 18;393(6686):684-8 PMID: 9641678
  21. Identification of SOCS-3 as a potential mediator of central leptin resistance.
    Mol Cell. 1998 Mar;1(4):619-25 PMID: 9660946
  22. Type 2 diabetes--who is conducting the orchestra?
    Nat Genet. 1998 Nov;20(3):223-5 PMID: 9806535
  23. Intracerebroventricular leptin regulates hepatic but not peripheral glucose fluxes.
    J Biol Chem. 1998 Nov 20;273(47):31160-7 PMID: 9813020
  24. Characterization of the neuroanatomical distribution of agouti-related protein immunoreactivity in the rhesus monkey and the rat.
    Endocrinology. 1999 Mar;140(3):1408-15 PMID: 10067869
  25. The effect of leptin on Lep expression is tissue-specific and nutritionally regulated.
    Nat Med. 1999 Aug;5(8):895-9 PMID: 10426312
  26. Decreased visceral adiposity accounts for leptin effect on hepatic but not peripheral insulin action.
    Am J Physiol. 1999 Aug;277(2 Pt 1):E291-8 PMID: 10444425
  27. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy.
    Nature. 1999 Sep 2;401(6748):73-6 PMID: 10485707
  28. The central melanocortin system can directly regulate serum insulin levels.
    Endocrinology. 2000 Sep;141(9):3072-9 PMID: 10965876
  29. Positional cloning of the mouse obese gene and its human homologue.
    Nature. 1994 Dec 1;372(6505):425-32 PMID: 7984236
  30. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats.
    J Clin Invest. 1987 May;79(5):1510-5 PMID: 3571496
  31. Metabolic implications of body fat distribution.
    Diabetes Care. 1991 Dec;14(12):1132-43 PMID: 1773700
  32. Insulin resistance in visceral obesity.
    Int J Obes. 1991 Sep;15 Suppl 2:109-15 PMID: 1794931
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI12954
Published
2001-10-00
Pages
1079-85
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC200952
Subset
IM
Grants
NIDDK NIH HHS · R01 DK045024 · United States
NIDDK NIH HHS · DK-48321 · United States
NIDDK NIH HHS · DK-45024 · United States
NIDDK NIH HHS · R01 DK048321 · United States
NIDDK NIH HHS · P30 DK020541 · United States
NIDDK NIH HHS · DK-20541 · United States
NIDDK NIH HHS · P60 DK020541 · United States
NIDDK NIH HHS · R37 DK048321 · United States
Corrections
CommentIn
PMID: 11581296
External Links
PubMed source DOI: 10.1172/JCI12954 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2