The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Philip L. Hooper, G. Balogh, Eric Rivas, Kylie Kavanagh, L. Vígh

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease.

Original languageEnglish
Pages (from-to)447-464
Number of pages18
JournalCell Stress and Chaperones
Volume19
Issue number4
DOIs
Publication statusPublished - 2014

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Medical problems
Type 2 Diabetes Mellitus
Exercise
Sirtuins
Health
Therapeutics
Heat-Shock Response
Defects
Membrane structures
Induced Hyperthermia
AMP-Activated Protein Kinases
Adiposity
Glycosylated Hemoglobin A
Immersion
Membrane Lipids
Heat-Shock Proteins
Metabolic Networks and Pathways
Insulin Resistance
Comorbidity
Weight Loss

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Medicine(all)

Cite this

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes. / Hooper, Philip L.; Balogh, G.; Rivas, Eric; Kavanagh, Kylie; Vígh, L.

In: Cell Stress and Chaperones, Vol. 19, No. 4, 2014, p. 447-464.

Research output: Contribution to journalArticle

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