Hisataka Moriwaki

TL;DR: It was demonstrated that delay in gastric emptying did not differ between untreated, early-stage and treated, advanced-stage PD patients and healthy volunteers, and it was found that delayed gastric dumping may be one of markers of the pre-clinical stage of PD.

TL;DR: Metformin may be a potent candidate for chemoprevention of liver tumorigenesis in patients with obesity or diabetes by ameliorating insulin sensitivity, inhibiting the activation of Akt/mTOR/p70S6 signaling, and improving adipokine imbalance.

TL;DR: Whether inhibition of antiapoptotic pathways influences the susceptibility of mice to TNF‐α and phosphatidylinositol 3‐kinase (PI3K)‐regulated serine/threonine kinase Akt.

Abstract: Acid sphingomyelinase (ASM) regulates the homeostasis of sphingolipids, including ceramides and sphingosine‐1‐phosphate (S1P). Because sphingolipids regulate AKT activation, we investigated the role of ASM in hepatic glucose and lipid metabolism. Initially, we overexpressed ASM in the livers of wild‐type and diabetic db/db mice by adenovirus vector (Ad5ASM). In these mice, glucose tolerance was improved, and glycogen and lipid accumulation in the liver were increased. Using primary cultured hepatocytes, we confirmed that ASM increased glucose uptake, glycogen deposition, and lipid accumulation through activation of AKT and glycogen synthase kinase‐3β. In addition, ASM induced up‐regulation of glucose transporter 2 accompanied by suppression of AMP‐activated protein kinase (AMPK) phosphorylation. Loss of sphingosine kinase‐1 (SphK1) diminished ASM‐mediated AKT phosphorylation, but exogenous S1P induced AKT activation in hepatocytes. In contrast, SphK1 deficiency did not affect AMPK activation. These results suggest that the SphK/S1P pathway is required for ASM‐mediated AKT activation but not for AMPK inactivation. Finally, we found that treatment with high‐dose glucose increased glycogen deposition and lipid accumulation in wild‐type hepatocytes but not in ASM_/_ cells. This result is consistent with glucose intolerance in ASM_/_ mice. In conclusion, ASM modulates AKT activation and AMPK inactivation, thus regulating glucose and lipid metabolism in the liver.—Osawa, Y., Seki, E., Kodama, Y., Suetsugu, A., Miura, K., Adachi, M., Ito, H., Shiratori, Y., Banno, Y., Olefsky, J. M., Nagaki, M., Moriwaki, H., Brenner, D. A., Seishima, M. Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP‐activated protein kinase suppression. FASEBJ. 25, 1133‐1144 (2011). www.fasebj.org