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

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.

Heat shock protein production and immunity and altered fetal development in diabetic pregnant rats

“…Similarly, hsp60 and hsp70 were found to be induced in lymphocytes of patients suffering from type-2 diabetic nephropathy compared to controls (Calabrese et al 2007). In contrast, other studies have reported reduced systemic hsp70 expression in association with elevated glucose levels in both humans (Bruce et al 2003;Chung et al 2008) and non-human primates (Kavanagh et al 2009). This apparent discrepancy remains to be resolved.…”

“…Elevated glucose levels are highly associated with reduced systemic hsp70 expression in both humans (Chung et al 2008) and non-human primates (Kavanagh et al 2009). A possible mechanism is suggested by the observation that the ingestion of glucose resulted in a decreased ability to induce hsp70 (Febbraio et al 2004).…”

Hamartin-Hsp70 Interaction Is Necessary for Akt-Dependent Tuberin Phosphorylation during Heat Shock

“…26) In addition, the levels of Hsp70 in muscle are associated with patients with insulin resistance and their first-degree relatives. 27,28) Hence, we suppose that our findings contribute to understanding of the mechanisms of insulin resistance through tuberin degradation and hamartin-Hsp70 functions. This process leads to tuberin degradation, and hamartin-Hsp70 interaction has a further unknown role (Fig.…”

Potential nutritional strategies for the amelioration or prevention of high rigor temperature in cattle – a review

“…Furthermore, HSPs may offer mitochondrial protection by preventing damage to oxidation processes (Gupte et al 2008). Intriguingly, people with an inherited reduced capacity to synthesise HSPs, as well as ageing populations, have an increased risk of developing insulin resistance (McCarty 2006;Kavanagh et al 2009). Chung et al (2008) showed the expression of HSP70, but not HSP90, protein in human skeletal muscle to be markedly reduced in insulin-resistant populations, and in the skeletal muscle of type 2 diabetic humans, HSP70 expression was decreased.…”