These results indicate that GLP-1 receptor agonists may prevent disease progression in the early stage of diabetic nephropathy through direct effects on the GLP-1 receptor in kidney tissue.

Inflammatory process is involved in the pathogenesis of diabetic nephropathy. In this article, we show that cholecystokinin (CCK) is expressed in the kidney and exerts renoprotective effects through its anti-inflammatory actions. DNA microarray showed that CCK was upregulated in the kidney of diabetic wild-type (WT) mice but not in diabetic intracellular adhesion molecule-1 knockout mice. We induced diabetes in CCK-1 receptor (CCK-1R) and CCK-2R double-knockout (CCK-1R−/−,-2R−/−) mice, and furthermore, we performed a bone marrow transplantation study using CCK-1R−/− mice to determine the role of CCK-1R on macrophages in the diabetic kidney. Diabetic CCK-1R−/−,-2R−/− mice revealed enhanced albuminuria and inflammation in the kidney compared with diabetic WT mice. In addition, diabetic WT mice with CCK-1R−/− bone marrow–derived cells developed more albuminuria than diabetic CCK-1R−/− mice with WT bone marrow–derived cells. Administration of sulfated cholecystokinin octapeptide (CCK-8S) ameliorated albuminuria, podocyte loss, expression of proinflammatory genes, and infiltration of macrophages in the kidneys of diabetic rats. Furthermore, CCK-8S inhibited both expression of tumor necrosis factor-α and chemotaxis in cultured THP-1 cells. These results suggest that CCK suppresses the activation of macrophage and expression of proinflammatory genes in diabetic kidney. Our findings may provide a novel strategy of therapy for the early stage of diabetic nephropathy.

Aims/hypothesis: Recent studies have shown that the inflammatory process is involved in the pathogenesis of diabetic nephropathy. Fourteen-membered ring macrolides, including erythromycin, have anti-inflammatory, as well as antibacterial effects. The aim of this study was to investigate the renoprotective effects of erythromycin in streptozotocin (STZ)-induced diabetic rats. Methods: STZinduced diabetic rats were treated orally with erythromycin (5 mg/kg body weight) or vehicle every day for 8 weeks.To evaluate the effect of erythromycin treatment, we measured urinary albumin excretion, and examined the following in the kidney: histological changes, the expression of intercellular adhesion molecule-1 (ICAM-1), macrophage infiltration, and nuclear factor-kappa B (NF-κB) activity. Results: Erythromycin significantly reduced urinary albumin excretion without affecting blood glucose levels and blood pressure. Erythromycin also attenuated glomerular hypertrophy, mesangial expansion, macrophage infiltration and ICAM-1 expression in renal tissues. The expression of the gene encoding TGFB1 (also known as TGF-β1), type IV collagen protein production and NF-κB activity in renal tissues were increased in diabetic rats and reduced by erythromycin treatment. Conclusions/ interpretation: Erythromycin prevented renal injuries without changes of blood glucose levels and blood pressure in experimental diabetic rats. These results suggest that the renoprotective effects of erythromycin are based on its anti-inflammatory effect via suppression of NF-κB activation. Modulation of microinflammation with erythromycin may provide a new approach for diabetic nephropathy.

OBJECTIVEAn inflammatory process is involved in the mechanism of obesity-related insulin resistance. Recent studies indicate that monocyte chemoattractant protein-1 (MCP-1) is a major chemokine that promotes monocyte infiltration into adipose tissues; however, the adhesion pathway in adipose tissues remains unclear. We aimed to clarify the adhesion molecules that mediate monocyte infiltration into adipose tissue.RESEARCH DESIGN AND METHODSWe used a DNA microarray to compare the gene expression profiles in epididymal white adipose tissues (eWAT) between db/db mice and C57/BL6 mice each fed a high-fat diet (HFD) or a low-fat diet (LFD). We investigated the change of insulin resistance and inflammation in eWAT in P-selectin glycoprotein ligand-1 (PSGL-1) homozygous knockout (PSGL-1−/−) mice compared with wild-type (WT) mice fed HFD.RESULTSDNA microarray analysis revealed that PSGL-1, a major ligand for selectins, is upregulated in eWAT from both db/db mice and WT mice fed HFD. Quantitative real-time RT-PCR and immunohistochemistry showed that PSGL-1 is expressed on both endothelial cells and macrophages in eWAT of obese mice. PSGL-1−/− mice fed HFD showed a remarkable reduction of macrophage accumulation and expression of proinflammatory genes, including MCP-1 in eWAT. Moreover, adipocyte hypertrophy, insulin resistance, lipid metabolism, and hepatic fatty change were improved in PSGL-1−/− mice compared with WT mice fed HFD.CONCLUSIONSThese results indicate that PSGL-1 is a crucial adhesion molecule for the recruitment of monocytes into adipose tissues in obese mice, making it a candidate for a novel therapeutic target for the prevention of obesity-related insulin resistance.

Paraganglioma of the gastrointestinal tract is an uncommon, usually benign neoplasm. It usually occurs in the second section of the duodenum. A review of the literature reveals 73 reported cases. We studied a case of paraganglioma by hypotonic duodenography (HDG), computed tomography (CT), angiography and histological examination. The rare occurrence of this neoplasm and the first comparative study using HDG, CT and angiography justify this case report. A 65-year-old Japanese woman had been in excellent health until she presented to her physician with tarry stool. The bleeding site was not determined. Seven months later, she visited another physician because of general fatigue, and was found to be anaemic and bleeding from the gastrointestinal tract. She was referred to the Kawasaki Medical School Hospital for further evaluation. On admission, she was moderately anaemic but not jaundiced. The abdomen was flat and soft without rebound tenderness. A slightly rough-surfaced, gooseegg sized mass was palpable in the right upper quadrant of the abdomen which moved with respiration but was not tender. Routine laboratory examination showed no abnormalities except anaemia. A hypotonic duodenogram showed a relatively smoothedged filling defect with a deep and irregular niche on the lateral wall of the second portion of the duodenum (Fig. 1). Contrast-enhanced CT revealed an inhomogeneous mass of soft-tissue density along the lateral aspect of the duodenum. This study was carried out with Gastrografin so that the mass could be easily demonstrated (Fig. 2).