title: Augmented beta cell loss and mitochondrial abnormalities in sucrose-fed GK rats.
abstract: Progressive decline of islet beta cell mass is a hallmark of type 2 diabetes, where nutritional insults are invoked in the pathologic process. Its detailed mechanisms are, however, incompletely understood. We explored the effect of sucrose diet on mitochondria in Goto Kakizaki (GK) rats, a spontaneously diabetic model. Six-week-old male GK rats were given 30% sucrose orally for 2 weeks. Normal Wistar rats fed with sucrose served as controls. Compared to untreated GK rats, sucrose-fed GK rats showed severe degeneration and death of beta cells with disrupted and swollen mitochondria and a greater beta cell loss. Submicroscopic analysis disclosed a smaller mean volume and a greater number of mitochondria in beta cells in GK rats compared to those in Wistar rats. Mitochondria in sucrose-fed GK rats were 2.4-fold greater in mean volume than those in untreated state. Without sucrose feeding, there was no significant difference in mitochondrial membrane potentials (MmPs) of isolated islets between Wistar and GK rats. MmPs were reduced by 44% in sucrose-fed GK rats but not influenced in sucrose-fed Wistar rats. Current results suggest that nutritional insults like sucrose feeding may exert deleterious effects on mitochondria, resulting in augmented beta cell loss in type 2 diabetes.
authors.affiliation: Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Wada
authors.forename: Motoi
authors.initials: M
authors.lastname: Koyama
authors.forename: Teruko
authors.initials: T
authors.lastname: Takeo
authors.forename: Sechiko
authors.initials: S
authors.lastname: Suga
authors.forename: Makoto
authors.initials: M
authors.lastname: Wakui
authors.forename: Soroku
authors.initials: S
authors.lastname: Yagihashi
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D019422:Dietary Sucrose / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D019422:Dietary Sucrose; D007328:Insulin