Effects of calcineurin activation on insulin-, AICAR- and contraction-induced glucose transport in skeletal muscle.

Abstract

Skeletal muscle is composed of fast- and slow-twitch fibres with distinctive physiological and metabolic properties. The calmodulin-activated serine/threonine protein phosphatase calcineurin activates fast- to slow-twitch skeletal muscle remodelling through the induction of the slow-twitch skeletal muscle fibre gene expression programme, thereby enhancing insulin-stimulated glucose uptake and offering protection against dietary-induced insulin resistance. Given the profound influence of skeletal muscle fibre type on insulin-mediated responses, we determined whether the fast- to slow-twitch fibre-type transformation leads to alterations in insulin-independent glucose uptake in transgenic mice expressing a constitutively active form of calcineurin (MCK-CnA* mice). We determined whether skeletal muscle remodelling by activated calcineurin alters glucose transport in response to the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-beta-D-ribofuranoside (AICAR) or muscle contraction, two divergent insulin-independent activators of glucose transport. While insulin-stimulated glucose transport was increased 52%, the AICAR effect on glucose transport was 27% lower in MCK-CnA* mice versus wild-type mice (P < 0.05). In contrast, glucose transport was similar between genotypes after in vitro muscle contraction. Fibre-type transformation was associated with increased AMPKgamma1, decreased AMPKgamma3 and unchanged AMPKgamma2 protein expression between MCK-CnA* and wild-type mice (P < 0.05). The loss of AICAR-mediated glucose uptake is coupled to changes in the AMPK isoform expression, suggesting fibre-type dependence of the AICAR responses on glucose uptake. In conclusion, improvements in skeletal muscle glucose transport in response to calcineurin-induced muscle remodelling are limited to insulin action.

• Authors: Jeffrey W Ryder, Yun Chau Long, Elisabeth Nilsson, Margit Mahlapuu, Juleen R Zierath
• Journal: The Journal of physiology (J Physiol) Vol. 567 Issue Pt 2 Pg. 379-86 (Sep 01 2005) ISSN: 0022-3751 [Print] England
• PMID: 15975979 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Multienzyme Complexes
• Ribonucleotides
• Aminoimidazole Carboxamide
• Protein Serine-Threonine Kinases
• AMP-Activated Protein Kinases
• Calcineurin
• AICA ribonucleotide
• Glucose

Topics

• AMP-Activated Protein Kinases
• Aminoimidazole Carboxamide (analogs & derivatives, metabolism)
• Animals
• Biological Transport, Active
• Calcineurin (metabolism)
• Electric Stimulation
• Glucose (metabolism)
• Insulin (metabolism)
• Isometric Contraction (physiology)
• Mice
• Mice, Transgenic
• Multienzyme Complexes (metabolism)
• Muscle, Skeletal (physiology)
• Protein Serine-Threonine Kinases (metabolism)
• Ribonucleotides (metabolism)
• Signal Transduction (physiology)