title: Protective effects of fish oil and pioglitazone on pancreatic tissue in obese KK mice with type 2 diabetes.
abstract: n-3 Polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have protective effects against the pancreatic β-cell dysfunction through several mechanisms. Thiazolidines are insulin sensitizers and are used in treating patients with type 2 diabetes. Our previous study demonstrated that a combination of fish oil, which is rich with EPA and DHA, and pioglitazone exerts beneficial effects on obesity and diabetes through their actions on the liver and adipose tissue. However, it remains largely unknown whether such combination therapy affects the pancreas. To answer this question, KK mice, which serve as a model for obesity and type 2 diabetes, were treated for 8 weeks with fish oil and pioglitazone. The combined regimen suppressed pancreatic islet hypertrophy (mean islet area decreased by an average of 49% vs. control) compared with mice treated with fish oil or pioglitazone alone (decreased by an average of 21% and 32% vs. control, respectively). Compared with the controls, individual or combined treatment significantly increased the percentage of β-cell area in the pancreatic islets, significantly decreased endoplasmic reticulum stress, and reduced the percentage of apoptotic cell death in the pancreatic islets. These findings suggest that fish oil and/or pioglitazone prevents β-cell dysfunction by improving the insulin resistance and decreasing the ER stress.
authors.affiliation: Department of Clinical Dietetics & Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Iizuka
authors.affiliation: Department of Clinical Dietetics & Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan. Electronic address: hyounju@josai.ac.jp.
authors.forename: Hyounju
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Clinical Dietetics & Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Izawa
authors.affiliation: Department of Clinical Dietetics & Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Sakurai
authors.affiliation: Department of Health and Nutrition, University of Human Arts and Sciences, Saitama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirako
authors.affiliation: Department of Clinical Dietetics & Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Wada
authors.affiliation: Department of Clinical Dietetics & Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
authors.forename: Akiyo
authors.initials: A
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005395:Fish Oils / Q000008:administration & dosage* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D016207:Cytokines; D005395:Fish Oils; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: Fish oil; Islet hypertrophy; Pioglitazone; Protective effect; β-cell dysfunction