title: Hyperthermia with mild electrical stimulation protects pancreatic β-cells from cell stresses and apoptosis.
abstract: Induction of heat shock protein (HSP) 72 improves metabolic profiles in diabetic model mice. However, its effect on pancreatic β-cells is not known. The current study investigated whether HSP72 induction can reduce β-cell stress signaling and apoptosis and preserve β-cell mass. MIN6 cells and db/db mice were sham-treated or treated with heat shock (HS) and mild electrical stimulation (MES) (HS+MES) to induce HSP72. Several cellular markers, metabolic parameters, and β-cell mass were evaluated. HS+MES treatment or HSP72 overexpression increased HSP72 protein levels and decreased tumor necrosis factor (TNF)-α-induced Jun NH(2)-terminal kinase (JNK) phosphorylation, endoplasmic reticulum (ER) stress, and proapoptotic signal in MIN6 cells. In db/db mice, HS+MES treatment for 12 weeks significantly improved insulin sensitivity and glucose homeostasis. Upon glucose challenge, a significant increase in insulin secretion was observed in vivo. Compared with sham treatment, levels of HSP72, insulin, pancreatic duodenal homeobox-1, GLUT2, and insulin receptor substrate-2 were upregulated in the pancreatic islets of HS+MES-treated mice, whereas JNK phosphorylation, nuclear translocation of forkhead box class O-1, and nuclear factor-κB p65 were reduced. Apoptotic signals, ER stress, and oxidative stress markers were attenuated. Thus, HSP72 induction by HS+MES treatment protects β-cells from apoptosis by attenuating JNK activation and cell stresses. HS+MES combination therapy may preserve pancreatic β-cell volume to ameliorate glucose homeostasis in diabetes.
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kondo
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sasaki
authors.forename: Rina
authors.initials: R
authors.lastname: Matsuyama
authors.forename: Saori
authors.initials: S
authors.lastname: Morino-Koga
authors.forename: Hironori
authors.initials: H
authors.lastname: Adachi
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Suico
authors.forename: Junji
authors.initials: J
authors.lastname: Kawashima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Motoshima
authors.forename: Noboru
authors.initials: N
authors.lastname: Furukawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kai
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001835:Body Weight; D004435:Eating; D004558:Electric Stimulation; D004721:Endoplasmic Reticulum / Q000502:physiology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006358:Hot Temperature; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000502:physiology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D010766:Phosphorylation; D013312:Stress, Physiological / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D050884:HSP72 Heat-Shock Proteins; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D048670:MAP Kinase Kinase 4; D005947:Glucose