Back to Search
Start Over
Effects of intravenous AICAR (5-aminoimidazole-4-carboximide riboside) administration on insulin signaling and resistance in premature baboons, Papio sp
- Source :
- PLoS ONE, PLoS ONE, Vol 13, Iss 12, p e0208757 (2018)
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
Abstract
- Premature baboons exhibit peripheral insulin resistance and impaired insulin signaling. 5' AMP-activated protein kinase (AMPK) activation improves insulin sensitivity by enhancing glucose uptake (via increased glucose transporter type 4 [GLUT4] translocation and activation of the extracellular signal-regulated kinase [ERK]/ atypical protein kinase C [aPKC] pathway), and increasing fatty acid oxidation (via inhibition of acetyl-CoA carboxylase 1 [ACC]), while downregulating gluconeogenesis (via induction of small heterodimer partner [SHP] and subsequent downregulation of the gluconeogenic enzymes: phosphoenolpyruvate carboxykinase [PEPCK], glucose 6-phosphatase [G6PASE], fructose- 1,6-bisphosphatase 1 [FBP1], and forkhead box protein 1 [FOXO1]). The purpose of this study was to investigate whether pharmacologic activation of AMPK with AICAR (5-aminoimidazole-4-carboximide riboside) administration improves peripheral insulin sensitivity in preterm baboons. 11 baboons were delivered prematurely at 125±2 days (67%) gestation. 5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1. 6 animals were in the placebo group. Euglycemic hyperinsulinemic clamps were performed at 5±2 and 14±2 days of life. Key molecules potentially altered by AICAR (AMPK, GLUT4, ACC, PEPCK, G6PASE, FBP1, and FOXO1), and the insulin signaling molecules: insulin receptor (INSR), insulin receptor substrate 1 (IRS-1), protein kinase B (AKT), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were measured using RT-PCR and western blotting. AICAR infusion did not improve whole body insulin-stimulated glucose disposal in preterm baboons (12.8±2.4 vs 12.4±2.0 mg/(kg·min), p = 0.8, placebo vs AICAR). One animal developed complications during treatment. In skeletal muscle, AICAR infusion did not increase phosphorylation of ACC, AKT, or AMPK whereas it increased mRNA expression of ACACA (ACC), AKT, and PPARGC1A (PGC1α). In the liver, INSR, IRS1, G6PC3, AKT, PCK1, FOXO1, and FBP1 were unchanged, whereas PPARGC1A mRNA expression increased after AICAR infusion. This study provides evidence that AICAR does not improve insulin sensitivity in premature euglycemic baboons, and may have adverse effects.
- Subjects :
- Male
0301 basic medicine
Physiology
medicine.medical_treatment
Muscle Proteins
FOXO1
Monkeys
Fatty Acids, Nonesterified
Biochemistry
Random Allocation
Endocrinology
0302 clinical medicine
Baboons
Medicine and Health Sciences
Insulin
Post-Translational Modification
Phosphorylation
Musculoskeletal System
Mammals
Multidisciplinary
biology
Organic Compounds
Chemistry
Muscles
Monosaccharides
Eukaryota
Liver
Vertebrates
Physical Sciences
Medicine
Administration, Intravenous
Female
Anatomy
Glycogen
Research Article
Primates
medicine.medical_specialty
Science
Carbohydrates
030209 endocrinology & metabolism
03 medical and health sciences
Insulin resistance
Internal medicine
Old World monkeys
medicine
Animals
Hypoglycemic Agents
RNA, Messenger
Muscle, Skeletal
Protein kinase B
Diabetic Endocrinology
Endocrine Physiology
Organic Chemistry
Insulin Signaling
Organisms
Chemical Compounds
Biology and Life Sciences
Proteins
AMPK
Ribonucleotides
Aminoimidazole Carboxamide
medicine.disease
Hormones
IRS1
Insulin receptor
Glucose
030104 developmental biology
Skeletal Muscles
Animals, Newborn
Amniotes
biology.protein
Insulin Resistance
GLUT4
Papio
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....c79d68421a66872dc4ac03b77f888a6d