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Tissue-specific regulation and expression of heat shock proteins in type 2 diabetic monkeys

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Cell Stress and Chaperones Aims and scope

Abstract

The chaperone protein heat shock protein (HSP) 70 has been shown to protect against obesity-associated insulin resistance. Induction of HSPs is thus considered an exciting therapeutic strategy for diabetes (DM). The aims of this study were to (1) determine HSP levels in plasma, hepatic, and pancreatic tissues of type 2 DM primates and (2) assess the relationship between chaperone proteins of the HSP family and cellular protection. We collected plasma from 24 type 2 DM and 25 normoglycemic control (CTL) cynomolgus macaques. A subset of DM monkeys had liver and pancreas samples available which were compared to a second group of CTL monkeys. We found that DM monkeys had 32% lower HSP70 in circulation which remained significant even after adjustment for the greater age and bodyweight of these monkeys (p < 0.001). The liver demonstrated a similar reductions in both HSP70 and 90 that was related to 50% lower levels of the transcription factor, heat shock factor 1 (HSF1; p = 0.03). Pancreatic tissue had the opposite expression pattern with significantly higher HSF1 (p = 0.004) and accordingly higher HSP70 and 90. Pancreas from DM monkeys had less nitrosative oxidation (p = 0.03) which was unaccounted for by superoxide dismutases and was negatively associated with HSP levels (r = −0.57, p = 0.009). HSF1/HSP deficiency exists in DM liver which may contribute to hepatic insulin resistance and this deficiency was reflected in lower circulating concentrations. Pancreas maintains HSP levels despite hyperglycemia, likely in an attempt to protect vulnerable beta cells from exocrine pancreatic damage and from stress associated with insulin hypersecretion.

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Abbreviations

ADPN:

adiponectin

BW:

bodyweight

c-pep:

C-peptide

CRP:

C-reactive protein

CTL:

control

DM:

diabetes

DTT:

dithiothreitol

EDTA:

ethylenediaminetetraacetic acid

ER:

endoplasmic reticulum

FBG:

fasting blood glucose

IR:

insulin resistance

HSF1:

heat shock factor 1

HSP:

heat shock protein

IL-6:

interleukin-6

NADPH:

nicotinamide adenine dinucleotide phosphate

ox-LDL:

oxidized ApoB lipoprotein

SOD:

superoxide dismutase

SEM:

standard error of the mean

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Acknowledgements

Funding for this study was provided by NIH Cardiovascular Pathology Training Grant 5T32HL07115 (KK), Wake Forest University School of Medicine, and Pfizer. The authors gratefully recognize Mr. Mickey Flynn for his editorial assistance.

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  1. Department of Pathology, Section on Comparative Medicine, Wake Forest University, Medical Center Blvd., Winston-Salem, NC, 27157, USA

    K. Kavanagh, Li Zhang & Janice D. Wagner

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  1. K. Kavanagh
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  2. Li Zhang
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  3. Janice D. Wagner
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Correspondence to K. Kavanagh.

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Kavanagh, K., Zhang, L. & Wagner, J.D. Tissue-specific regulation and expression of heat shock proteins in type 2 diabetic monkeys. Cell Stress and Chaperones 14, 291–299 (2009). https://doi.org/10.1007/s12192-008-0084-7

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  • DOI: https://doi.org/10.1007/s12192-008-0084-7

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