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HSP and Diabetes

  • Martin WhithamEmail author
  • Mark A. Febbraio
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 5)

Abstract

As the prevalence of diabetes continues to rise, strategies that aim to prevent and treat the condition continue to gain importance. Obesity is thought to induce a state of low-grade inflammation, which ultimately disrupts insulin signalling and predisposes individuals to type II diabetes. In particular, TNFα, endoplasmic reticulum (ER) and oxidative stress all appear to be associated with obesity and stimulate inflammatory kinases such as c jun amino terminal kinase (JNK), inhibitor of NF-κβ kinase (IKK) and protein kinase C (PKC). These kinases in turn inhibit insulin signalling, predominantly through inhibitory phosphorylation of the insulin receptor substrate (IRS). The current chapter reviews the literature that describes this process and the potential that heat shock proteins have in preventing inflammatory disruption of insulin signalling. In particular, data are presented that demonstrate the role of Hsp72 in the prevention of insulin resistance in diet and genetic models of murine obesity. The role of HSP in the autoimmunity of type I diabetes is also discussed

Keywords

Obesity inflammation insulin resistance hydroxylamine derivatives autoimmunity 

Abbreviations

β-HAD

β-hydroxyacyl-CoA-dehydrogenase

ATM

adipose tissue macrophages

BB

biobreeding

CS

citrate synthase

DAG

diacylglycerol

ER

endoplasmic reticulum

ERK1

extracellular signal-regulated kinases

FFA

free fatty acid

GSK-3β

glycogen synthase kinase 3β

HFD

high fat diet

HO-1

haem-oxygenase

HOMA-IR

homeostatic model assessment of insulin resistance

HT

heat therapy

HSE

heat shock element

HSF

heat shock factor

HSP

heat shock proteins

IKK

inhibitor of NF-κβ kinase

IMTG

intramuscular triglyceride

IPGTT

intraperotineal glucose tolerance tests

IR

insulin receptor

IRS

insulin receptor substrate

JNK

c-jun amino terminal kinase

MEF

mouse embryonic fibroblasts

NHANES

National Health and Nutrition Examination survey

NOD

non-obese diabetic mice

NSAID

non-steroidal anti-inflammatory drugs

OLETF

Otsuka Long-Evans Tokushima Fatty rats

PBA

4-phenyl butyric acid

PERK

PKR-like kinase

PI

phosphatidylinositol

PIP3

phosphatidilinositol 3, 4, 5 triphosphate

PKA

protein kinase A

PKC

protein kinase C

ROS

reactive oxygen species

TNFα

tumor necrosis factor α

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.School of Sport, Health and Exercise Sciences, Bangor UniversityGwyneddUK
  2. 2.Division of Metabolism and Obesity, Cellular & Molecular Metabolism LaboratoryBaker IDI Heart & Diabetes InstituteMelbourneAustralia
  3. 3.Cellular & Molecular Metabolism LaboratoryBaker IDI Heart & Diabetes InstituteMelbourneAustralia

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