Effects of chronic antagonism of endocannabinoid-1 receptors on glucose tolerance and insulin action in skeletal muscles of lean and obese zucker rats

Katherine A. Lindborg, Stephan Jacob, Erik J Henriksen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background/Aims: Antagonism of the endocannabinoid receptor-1 (CB1R) directly improves whole-body metabolic parameters of insulin resistance. The present investigation determined the effects of chronic CB1R antagonism on whole-body and skeletal-muscle insulin action in insulin-sensitive lean and insulin-resistant obese Zucker rats. Methods: Animals were either fed ad libitum or in pairs, or treated with SR141716 (10 mg/kg i.p. for 14 days). Results: Food intake was significantly reduced (p < 0.05) after initial SR141716 treatment and remained decreased in both lean and obese animals until day 13. Fasting plasma glucose decreased (24%) and insulin increased (43%) in lean SR141716-treated (24%) rats compared to lean ad libitum-fed controls, but not in the corresponding obese groups. Fasting plasma free fatty acids were reduced by CB1R antagonism in lean (21%) and obese (42%) animals. Whole-body insulin sensitivity was increased (36%) in obese SR141716-treated rats compared to obese ad libitum-fed controls, which was associated with reduced insulin secretion during an oral glucose tolerance test. Insulin-stimulated glucose transport activity in the soleus was greatest in the respective SR141716-treated lean and obese groups compared to the corresponding ad libitum- and pair-fed controls. Chronic SR141716 treatment did not induce alterations in signaling factors associated with the regulation of glucose transport [protein kinase B (Akt), glycogen synthase kinase-3β, 5′-AMP-dependent protein kinase, or p38 mitogen-activated protein kinase] in the soleus. Conclusions: These results indicate that, while the chronic treatment with CB1R antagonism markedly diminished food intake in lean and obese Zucker rats, there are also significant metabolic improvements in whole-body and skeletal-muscle insulin action mediated by CB1R antagonism through mechanisms independent of reduced caloric intake.

Original languageEnglish (US)
Pages (from-to)31-44
Number of pages14
JournalCardioRenal Medicine
Volume1
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

rimonabant
Zucker Rats
Endocannabinoids
Skeletal Muscle
Insulin
Insulin Resistance
Fasting
Eating
Glycogen Synthase Kinase 3
Glucose
Proto-Oncogene Proteins c-akt
Facilitative Glucose Transport Proteins
p38 Mitogen-Activated Protein Kinases
Adenosine Monophosphate
Glucose Tolerance Test
glucose receptor
Energy Intake
Nonesterified Fatty Acids
Protein Kinases

Keywords

  • CB1 receptor
  • Insulin resistance
  • Soleus muscle
  • SR141716
  • Zucker rat

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Urology

Cite this

Effects of chronic antagonism of endocannabinoid-1 receptors on glucose tolerance and insulin action in skeletal muscles of lean and obese zucker rats. / Lindborg, Katherine A.; Jacob, Stephan; Henriksen, Erik J.

In: CardioRenal Medicine, Vol. 1, No. 1, 01.2011, p. 31-44.

Research output: Contribution to journalArticle

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