Tissue-specific regulation and expression of heat shock proteins in type 2 diabetic monkeys.
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.
Department of Pathology, Wake Forest University, Winston-Salem, NC 27157, USA. kkavanag@wfubmc.edu
K
K
Kavanagh
Li
L
Zhang
Janice D
JD
Wagner
D000367:Age Factors; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008252:Macaca fascicularis; D010179:Pancreas / Q000378:metabolism; D012044:Regression Analysis; D014018:Tissue Distribution
D006360:Heat-Shock Proteins