Loss of Skeletal Muscle PKC Theta Protects Against The Pathogenesis of Insulin Resistance

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Peck, B. (2016). Loss of Skeletal Muscle PKC Theta Protects Against The Pathogenesis of Insulin Resistance. Unc Charlotte Electronic Theses And Dissertations.
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Abstract

Skeletal muscle is a primary regulator of glucose homeostasis, accounting for the majority of post-prandial glucose disposal. However states of skeletal muscle insulin-resistance result in severely attenuated glucose uptake and consequently hyperglycemia. The underlying cause of insulin-resistance in obese populations is currently theorized to be the consequence of lipotoxicity, but as of yet the intramyocellular mechanisms for this response remain elusive. Lipid intermediates such as diacylglycerol possess a high affinity for ligand binding/activation of protein kinase C (PKC) isoforms. PKC isoform θ specifically, has a strong correlation with lipid accumulation and insulin-stimulated glucose uptake inhibition. In order to investigate PKCθ’s role in skeletal muscle insulin-resistance, a muscle specific PKCθ knock out mouse model was employed followed by a 15 week high fat diet. The phenotype exhibited by our skeletal muscle PKCθ knock out mice is one of reduced weight gain, lipid accumulation, inflammation, and insulin resistance compared to wild type controls. The immunity to such deleterious effects regularly witnessed in high fat fed wild type mice further illustrates the prominent manner by which PKCθ induces skeletal muscle insulin-resistance.

Details
Author

Peck, Bailey

Title

Loss of Skeletal Muscle PKC Theta Protects Against The Pathogenesis of Insulin Resistance

Physical Description

1 online resource (48 pages) : PDF

Date

2016

Degree Granting Institution

University of North Carolina at Charlotte

Abstract

Skeletal muscle is a primary regulator of glucose homeostasis, accounting for the majority of post-prandial glucose disposal. However states of skeletal muscle insulin-resistance result in severely attenuated glucose uptake and consequently hyperglycemia. The underlying cause of insulin-resistance in obese populations is currently theorized to be the consequence of lipotoxicity, but as of yet the intramyocellular mechanisms for this response remain elusive. Lipid intermediates such as diacylglycerol possess a high affinity for ligand binding/activation of protein kinase C (PKC) isoforms. PKC isoform θ specifically, has a strong correlation with lipid accumulation and insulin-stimulated glucose uptake inhibition. In order to investigate PKCθ’s role in skeletal muscle insulin-resistance, a muscle specific PKCθ knock out mouse model was employed followed by a 15 week high fat diet. The phenotype exhibited by our skeletal muscle PKCθ knock out mice is one of reduced weight gain, lipid accumulation, inflammation, and insulin resistance compared to wild type controls. The immunity to such deleterious effects regularly witnessed in high fat fed wild type mice further illustrates the prominent manner by which PKCθ induces skeletal muscle insulin-resistance.

Genre

masters theses

Subjects--Topics

Molecular biology
Medical sciences

Degree

M.S.

Keywords

High Fat Diet
Insulin Resistance
PKC
Skeletal Muscle

Subject Area

Kinesiology

Advisor(s)

Marino, Joseph

Committee Members

Arthur, Susan
Bennett, Jeanette
Hinds, Terry

Degree Note

Thesis (M.S.)--University of North Carolina at Charlotte, 2016.

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Rights Holder Information

Copyright is held by the author unless otherwise indicated.

Identifier

Peck_uncc_0694N_11120

Permalink

http://hdl.handle.net/20.500.13093/etd:354