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Masato Kasuga

Publications and source records attributed to Masato Kasuga.

116 records · Page 7Linked to original sources

Effects of agouti-related protein, orexin and melanin-concentrating hormone on oxygen consumption in mice.

Neuropeptides in the hypothalamus play a pivotal role in the regulation of energy balance. Agouti-related protein (AGRP), orexin and melanin-concentrating hormone (MCH) have been identified in the hypothalamus as orexigenic peptides. This study was undertaken to investigate the effects of AGRP, orexin and MCH on oxygen consumption. Oxygen consumption was determined by an O2/CO2 metabolism measuring system at 22 degrees C. Mice were kept unrestrained in the chamber without food or water during the light cycle, and the oxygen consumption was measured for 2 h after intra-cerebroventricular (ICV) administration. ICV administered AGRP (1 nmol/mouse) significantly decreased oxygen consumption compared to ACSF-treated controls. Orexin (1 nmol/mouse) significantly increased oxygen consumption, while MCH (1 nmol/mouse) had no significant effect compared to ACSF-treated controls. These results suggest that AGRP, orexin and MCH might have different effects on energy expenditure, thereby regulating appetite and body weight.

Agouti-Related Protein↗

In vivo administration of glucosamine inhibited phosphatidylinositol 3-kinase activity without affecting tyrosine phosphorylation of the insulin receptor or insulin receptor substrate in rat adipocytes.

We examined insulin signaling in rat epididymal adipocytes which developed insulin resistance by the in vivo infusion of glucosamine. Insulin-stimulated 2-deoxyglucose uptake into the adipocytes isolated from rats which were infused glucosamine for 4 hours was diminished by 26%. To analyze insulin signaling in adipocytes, the epididymal fat tissues were harvested 5 minutes after insulin administration (10U/kg), which was administered immediately after glucosamine infusion. Glucosamine had no effect on the insulin-stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS)-1. Glucosamine infusion decreased insulin-stimulated phosphatidylinositol (PI) 3-kinase activity by 66%. Glucosamine infusion also inhibited insulin-stimulated PI 3-kinase activity associated with IRS-1, 2, 3 by 30%, 43%, and 44%, respectively. There was no difference in the association of the 85kDa subunit of PI 3-kinase with the IRS-1 and IRS-2 protein. PI 3-kinase activity in adipocytes from rats treated with glucosamine that were administered platelet derived growth factor (3microg/kg) for 5 minutes was also reduced by 39%. When we measured the kinase activity of protein kinase C (PKC) lamda, which is the downstream effector of PI 3-kinase in isolated adipocytes, we found that glucosamine inhibited insulin stimulated PKClamda kinase activity by 33%. These results suggest that glucosamine infusion contributes to the development of insulin resistance by mainly modulating the PI 3-kinase molecules.

Adipocytes↗

Experimental studies on the role of fructose in the development of diabetic complications.

We examined the role of fructose in the development of diabetic complications. Compared with glucose, fructose increased the fluorescence intensity and the cross-linking of glycated collagen, and promoted the polymerization of proteins. Therefore fructose accelerated the production of advanced glycation end-products more than glucose. In addition, fructose enhanced the reactive oxygen or oxygen radical generation and the associated degeneration of proteins and lipids. These actions of fructose appeared to be due to the formation of dicarbonyl compounds such as 3-deoxyglucosone, a highly reactive intermediate product formed in the advanced glycation stage. These results suggest that fructose is closely involved not only in glycation but also in the polyol pathway and peroxidation reactions through free radical formation. Thus, fructose is considered to be a more critical reducing sugar associated with the progression of diabetic complications than it has been thought until now.

Aldehyde Reductase↗

Leptin treatment ameliorates anxiety in ob/ob obese mice.

We investigated whether or not administered leptin influences anxiety-like behavior in ob/ob mice. Repeated intraperitoneal administrations of leptin were continued for 5 days. Anxiety was assessed in the standard elevated plus maze. Body weight was measured daily. Repeated administrations of leptin significantly increased the percentage of the total number of entries in the open arms and the number of total entries. The body weight was significantly reduced by 13.2% after treatment. Leptin treatment ameliorated not only obesity but also anxiety in ob/ob mice. Our results indicate that the treatment of obesity may lead to the solution of psychological problems.

Animals↗

Ob/ob mice as a model of delayed gastric emptying.

Diabetic gastroparesis is a well-recognized delay of gastric emptying in diabetic patients. We assessed the gastric emptying rate in ob/ob mice, a genetic model of obesity and diabetes. The basal gastric emptying rate in 22- to 27-week-old ob/ob mice was significantly lower than that in 10- to 11-week-old ob/ob mice (P<.01). Our results indicate that the ob/ob mice are a useful model not only of glucose intolerance but also of delayed gastric emptying as a diabetic complication.

Aging↗

Response to interferon-alpha in chronic hepatitis B with and without precore mutant strain detected by mutation site-specific assay.

GOALS: We investigated whether the presence of precore mutant (stop codon mutation at codon 28) affects the response to interferon-alpha in patients with chronic hepatitis B. BACKGROUND: Mutations of hepatitis B virus (HBV) may influence the response to treatment. The association of precore mutant with the response to interferon is controversial. STUDY: Thirty-one Japanese patients with hepatitis B e antigen-positive chronic hepatitis were treated with natural interferon-alpha. HBV DNA with the precore mutation was assayed in serum using a mutation site-specific assay before and after treatment. RESULTS: Before treatment, precore mutant was detected in 22 cases (group A) and not detected in 9 cases (group B). Serum HBV DNA level before treatment was not different between the 2 groups. At the end of treatment, serum HBV DNA was decreased to undetectable levels in 13% (4 of 31). Six months after treatment, the percentage of cases with loss of hepatitis B e antigen and a decrease in the transaminase level to within the normal range was significantly higher in group B than in group A (67%, 18%, P = 0.015). CONCLUSIONS: Chronic hepatitis without precore mutant strain before treatment is more responsive to IFN-alpha.

Adult↗