Calpain-10 and insulin resistance in human skeletal muscle

Variation in the calpain-10 gene has been linked to a three-fold increased risk for type 2 diabetes in Pima Indian and some European populations. Furthermore, reduced skeletal muscle expression of calpain-10 is associated with reduced insulin mediated glucose disposal and carbohydrate oxidation. T...

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Main Author: Norton, Luke
Format: Thesis (University of Nottingham only)
Language:English
Published: 2007
Online Access:https://eprints.nottingham.ac.uk/11536/
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author Norton, Luke
author_facet Norton, Luke
author_sort Norton, Luke
building Nottingham Research Data Repository
collection Online Access
description Variation in the calpain-10 gene has been linked to a three-fold increased risk for type 2 diabetes in Pima Indian and some European populations. Furthermore, reduced skeletal muscle expression of calpain-10 is associated with reduced insulin mediated glucose disposal and carbohydrate oxidation. The skeletal muscle specific calpain-3 plays a key role in skeletal muscle integrity and has also been linked to insulin resistance in humans and rodents. The major aims of this thesis were to 1) investigate the hypothesis that alterations in insulin sensitivity in healthy humans would lead to significant changes in the mRNA and protein expression of calpain-10 and -3, 2) investigate the effect of hyperinsulinaemia and lipid availability on calpain-10 and -3 expression, 3) further address the role of genetic variation in the calpain-10 gene on glucose utilisation in humans and finally 4) investigate the expression of calpain-10 in skeletal muscle of type 2 diabetic patients. The studies in this thesis show for the first time that insulin resistance as a result of short term fasting or high fat availability is not associated with changes in calpain-10 and -3 mRNA and protein expression, providing evidence against an adaptive role for these genes in the development of fasting- and lipid-induced insulin resistance.
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spelling nottingham-115362025-02-28T11:14:06Z https://eprints.nottingham.ac.uk/11536/ Calpain-10 and insulin resistance in human skeletal muscle Norton, Luke Variation in the calpain-10 gene has been linked to a three-fold increased risk for type 2 diabetes in Pima Indian and some European populations. Furthermore, reduced skeletal muscle expression of calpain-10 is associated with reduced insulin mediated glucose disposal and carbohydrate oxidation. The skeletal muscle specific calpain-3 plays a key role in skeletal muscle integrity and has also been linked to insulin resistance in humans and rodents. The major aims of this thesis were to 1) investigate the hypothesis that alterations in insulin sensitivity in healthy humans would lead to significant changes in the mRNA and protein expression of calpain-10 and -3, 2) investigate the effect of hyperinsulinaemia and lipid availability on calpain-10 and -3 expression, 3) further address the role of genetic variation in the calpain-10 gene on glucose utilisation in humans and finally 4) investigate the expression of calpain-10 in skeletal muscle of type 2 diabetic patients. The studies in this thesis show for the first time that insulin resistance as a result of short term fasting or high fat availability is not associated with changes in calpain-10 and -3 mRNA and protein expression, providing evidence against an adaptive role for these genes in the development of fasting- and lipid-induced insulin resistance. 2007-07 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/11536/1/Thesis_final.pdf Norton, Luke (2007) Calpain-10 and insulin resistance in human skeletal muscle. PhD thesis, University of Nottingham.
spellingShingle Norton, Luke
Calpain-10 and insulin resistance in human skeletal muscle
title Calpain-10 and insulin resistance in human skeletal muscle
title_full Calpain-10 and insulin resistance in human skeletal muscle
title_fullStr Calpain-10 and insulin resistance in human skeletal muscle
title_full_unstemmed Calpain-10 and insulin resistance in human skeletal muscle
title_short Calpain-10 and insulin resistance in human skeletal muscle
title_sort calpain-10 and insulin resistance in human skeletal muscle
url https://eprints.nottingham.ac.uk/11536/