Biomedical subjects

Toshihiro Kojima

Publications and source records attributed to Toshihiro Kojima.

3 recordsLinked to original sources

PubMed2003

Decrease of beta-cells and increase of alpha-cells in a diabetic patient with mitochondrial DNA 3243 (A-->G) mutation.

We report here a case of a 53-year-old woman with mitochondrial 3243 (A-->G) mutation diabetes. Diabetes mellitus was diagnosed at 39 years of age. At 50 years of age, cardiomyopathy and hypothyroidism were noted. At 53 years of age, the patient was admitted to our hospital for treatment of necrotic ulceration of toes. However, she died of massive heart failure. Pathological examination at autopsy showed a decrease in size, number, and acidophilicity of islets in the pancreas. Immunohistochemical stain revealed a decrease in the beta-cell population to 20.5+/-9.2% and a relative increase in alpha-cell population to 48.6+/-11.5%.

Cardiomyopathy, Dilated↗

PubMed2002

Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells: reciprocal involvement of PKC-alpha and PPAR expression.

Glucose concentration may be an important factor in breast cancer cell proliferation, and the prevalence of breast cancer is high in diabetic patients. Leptin may also be an important factor since plasma levels of leptin correlated with TNM staging for breast cancer patients. The effects of glucose and leptin on breast cancer cell proliferation were evaluated by examining cell doubling time, DNA synthesis, levels of cell cycle related proteins, protein kinase C (PKC) isozyme expression, and peroxisome proliferator-activated receptor (PPAR) subtypes were determined following glucose exposure at normal (5.5 mM) and high (25 mM) concentrations with/without leptin in MCF-7 human breast cancer cells. In MCF-7 cells, leptin and high glucose stimulated cell proliferation as demonstrated by the increases in DNA synthesis and expression of cdk2 and cyclin D1. PKC-alpha, PPARgamma, and PPARalpha protein levels were up-regulated following leptin and high glucose treatment in drug-sensitive MCF-7 cells. However, there was no significant effect of leptin and high glucose on cell proliferation, DNA synthesis, levels of cell cycle proteins, PKC isozymes, or PPAR subtypes in multidrug-resistant human breast cancer NCI/ADR-RES cells. These results suggested that hyperglycemia and hyperleptinemia increase breast cancer cell proliferation through accelerated cell cycle progression with up-regulation of cdk2 and cyclin D1 levels. This suggests the involvement of PKC-alpha, PPARalpha, and PPARgamma.

Breast Neoplasms↗

PubMed2002

High glucose inhibits apoptosis in human coronary artery smooth muscle cells by increasing bcl-xL and bfl-1/A1.

Cardiovascular disease is a serious complication in diabetic patients. To elucidate the precise mechanisms of atherosclerosis in diabetic patients, the effects of high glucose concentration (25 mM) on apoptosis regulation and bcl-2 family protein expression in human coronary artery smooth muscle cells (CASMC) were examined. Treatment with a high level of glucose (25 mM) caused a significant decrease in apoptosis in CASMC compared with the same cells treated with a physiologically normal glucose concentration (5.5 mM) (23.9 +/- 2.4% vs. 16.5 +/- 1.8%; P < 0.01). With respect to apoptosis regulation, treatment of CASMC with high glucose concentration markedly increased mRNA expressions of bcl-xL and bfl-1/A1 compared with cells treated with normal glucose. High glucose induced phosphorylation of phosphatidylinositol 3-kinase (PI 3-K) and extracellular signal-regulated kinase (ERK)1/2 along with bcl-xL and bfl-1/A1 upregulation. These results suggest that high glucose suppresses apoptosis via upregulation of bcl-xL and bfl-1/A1 levels through PI 3-K and ERK1/2 pathways in CASMC. High glucose-induced increase in the expression of antiapoptotic proteins may be important in the development of atherosclerosis in diabetic patients.

Apoptosis↗