Title:The Heat Stress Response and Diabetes: More Room for Mitochondrial Implication
Volume: 22
Issue: 18
Author(s): Biljana Miova, Maja Dimitrovska, Suzana Dinevska-Kjovkarovska, Juan V. Esplugues and Nadezda Apostolova
Affiliation:
Keywords:
Mitochondria, diabetes mellitus, heat shock, cross-tolerance, heat stress proteins.
Abstract: Heat preconditioning is a rapid cellular adaptive mechanism shared by many cells/ organs / organisms
that results in synthesis and accumulation of heat shock proteins (HSPs), which are responsible for increased tolerance
and survival of animals during and after heat stress (HS). HSPs function as molecular chaperones by restoring
cellular homeostasis and promoting cell survival, and their major functions include protection of cells from injury
by preventing protein damage and aggregation. Abundant evidence points to the ability of one kind of stress caused
by external factors that induce primary adaptations in the organism to provide protection against additional stress
of the same or another type, a phenomenon known as cross-tolerance.
Diabetes mellitus (DM) is one of the diseases which have been associated with increased tissue sensitivity and vulnerability due to incorrect
protein folding. Thus, HSPs may play an important role in minimizing the protein damage that can occur under the stressful conditions
created by the disease. By increasing HSP production, heat preconditioning may be a promising therapy for patients with lifestylerelated
diseases such as hypercholesterolemia, hypertension, DM and obesity. Also, pancreatic β-cells exposed to acute HS activate defence
mechanisms which include HSP synthesis and are less sensitive to the effects of cytotoxic agents such as NO, oxygen radicals and
-cytotoxic diabetogenic agents, such as streptozotocin (STZ).
Mitochondrial dysfunction and mitochondria-specific cell stress are associated and can even be a primary abnormality caused by DMinduced
hyperglycaemia and oxidative stress. There are an increasing number of genetic and/or pharmacological modulations of HSPs
that have revealed the connection between HSPs, mitochondria and diabetes. HSPs may affect mitochondrial function in multiple ways,
but the influence on skeletal muscle and adipose tissue, as well as on the pancreas, has attracted most interest as a key element in the development
of novel pharmacological approaches to treating DM and associated metabolic conditions.