Tags

Type your tag names separated by a space and hit enter

Activation of insulin signaling and energy sensing network by AICAR, an AMPK activator in insulin resistant rat tissues.
J Basic Clin Physiol Pharmacol. 2015 Nov; 26(6):563-74.JB

Abstract

BACKGROUND

The energy status of the cell is regulated by the energy sensing network constituted by AMP-activated protein kinase (AMPK), the NAD+-dependent type III deacetylase silence information regulator T1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). This study investigates the potential effect of 5-aminoimidazole-4-carboximide-1-b-D-ribofuranoside (AICAR), an AMPK activator on insulin signaling and energy sensing network in insulin resistant rats.

METHODS

Adult male albino Wistar rats with body weight of 150-180 g were fed high-fructose diet (HFD) for 60 days to induce insulin resistance. Rats fed HFD were divided into two and were treated or untreated with AICAR (0.7 mg/kg bw, i.p.) for the last 2 weeks.

RESULTS

Insulin resistant rats displayed increased glucose and insulin levels and reduced tyrosine phosphorylation of insulin resistance receptor and insulin receptor substrate 1. The downstream signaling and glucose transport were also affected. Phosphorylation of AMPK, SIRT1 protein abundance and mRNA expression of PGC-1α were reduced. Treatment with AICAR reduced hyperglycemia and hyperinsulinemia and improved the activation of the key molecules of insulin signaling. Improved action of energy sensing network was noted after AICAR treatment. AICAR showed higher binding affinity with Akt (-8.2 kcal/mol) than with AMPK or insulin receptor (-8.0 kcal/mol) in the in silico study.

CONCLUSIONS

The findings suggest that AICAR, the AMPK activator, influences insulin signaling proteins and molecules involved in energy modulation during insulin resistance.

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26124049

Citation

Radika, Mutlur Krishnamoorthy, and Carani Venkatraman Anuradha. "Activation of Insulin Signaling and Energy Sensing Network By AICAR, an AMPK Activator in Insulin Resistant Rat Tissues." Journal of Basic and Clinical Physiology and Pharmacology, vol. 26, no. 6, 2015, pp. 563-74.
Radika MK, Anuradha CV. Activation of insulin signaling and energy sensing network by AICAR, an AMPK activator in insulin resistant rat tissues. J Basic Clin Physiol Pharmacol. 2015;26(6):563-74.
Radika, M. K., & Anuradha, C. V. (2015). Activation of insulin signaling and energy sensing network by AICAR, an AMPK activator in insulin resistant rat tissues. Journal of Basic and Clinical Physiology and Pharmacology, 26(6), 563-74. https://doi.org/10.1515/jbcpp-2014-0122
Radika MK, Anuradha CV. Activation of Insulin Signaling and Energy Sensing Network By AICAR, an AMPK Activator in Insulin Resistant Rat Tissues. J Basic Clin Physiol Pharmacol. 2015;26(6):563-74. PubMed PMID: 26124049.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of insulin signaling and energy sensing network by AICAR, an AMPK activator in insulin resistant rat tissues. AU - Radika,Mutlur Krishnamoorthy, AU - Anuradha,Carani Venkatraman, PY - 2014/11/14/received PY - 2015/04/23/accepted PY - 2015/7/1/entrez PY - 2015/7/1/pubmed PY - 2016/8/30/medline SP - 563 EP - 74 JF - Journal of basic and clinical physiology and pharmacology JO - J Basic Clin Physiol Pharmacol VL - 26 IS - 6 N2 - BACKGROUND: The energy status of the cell is regulated by the energy sensing network constituted by AMP-activated protein kinase (AMPK), the NAD+-dependent type III deacetylase silence information regulator T1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). This study investigates the potential effect of 5-aminoimidazole-4-carboximide-1-b-D-ribofuranoside (AICAR), an AMPK activator on insulin signaling and energy sensing network in insulin resistant rats. METHODS: Adult male albino Wistar rats with body weight of 150-180 g were fed high-fructose diet (HFD) for 60 days to induce insulin resistance. Rats fed HFD were divided into two and were treated or untreated with AICAR (0.7 mg/kg bw, i.p.) for the last 2 weeks. RESULTS: Insulin resistant rats displayed increased glucose and insulin levels and reduced tyrosine phosphorylation of insulin resistance receptor and insulin receptor substrate 1. The downstream signaling and glucose transport were also affected. Phosphorylation of AMPK, SIRT1 protein abundance and mRNA expression of PGC-1α were reduced. Treatment with AICAR reduced hyperglycemia and hyperinsulinemia and improved the activation of the key molecules of insulin signaling. Improved action of energy sensing network was noted after AICAR treatment. AICAR showed higher binding affinity with Akt (-8.2 kcal/mol) than with AMPK or insulin receptor (-8.0 kcal/mol) in the in silico study. CONCLUSIONS: The findings suggest that AICAR, the AMPK activator, influences insulin signaling proteins and molecules involved in energy modulation during insulin resistance. SN - 2191-0286 UR - https://www.unboundmedicine.com/medline/citation/26124049/Activation_of_insulin_signaling_and_energy_sensing_network_by_AICAR_an_AMPK_activator_in_insulin_resistant_rat_tissues_ L2 - https://www.degruyter.com/doi/10.1515/jbcpp-2014-0122 DB - PRIME DP - Unbound Medicine ER -