HMW-adiponectin associates with triglyceride concentrations in type 1 diabetic patients.

AIM: The objective of this study was to investigate the relation between serum high molecular weight (HMW)-adiponectin concentration and fasting and postprandial blood glycemic and lipid parameters in type 1 diabetic patients. METHODS: Type 1 diabetic patients treated with short-acting insulin analogs and healthy volunteers were recruited. The subjects were divided into two groups based on the mean HMW-adiponectin value of 12.2 mg/L: low HMW-adiponectin (men/women=7/2) and high HMW-adiponectin (men/women=3/8). Blood samples were collected after an overnight fast, and 30180 min after consuming white bread (B) or white bread with butter (BB). RESULTS: Type 1 diabetic patients with high HMW-adiponectin had lower triglyceride and remnant like particle (RLP)-triglyceride concentrations than those with low HMW-adiponectin (p<0.01), and had a higher lipoprotein lipase mass (p<0.01) than healthy subjects (men/women=8/6). After B and BB meals, type 1 diabetic patients with high HMW-adiponectin consistently had lower triglyceride and RLP-triglyceride concentrations for up to 180 min than those with low HMW-adiponectin (p<0.01); however, apoB48 did not differ between these two groups. Fasting and postprandial plasma glucose were higher in both diabetic groups than in healthy subjects (p<0.001), with no significant difference between patient groups. CONCLUSION: HMW-adiponectin is more strongly associated with very low density lipoprotein remnant metabolism than glucose utilization in type 1 diabetic patients receiving short-acting insulin analogs.

Is central obesity a good predictor of carotid atherosclerosis in Japanese type 2 diabetes with metabolic syndrome?

Metabolic syndrome has been revealed to be a major risk factor for cardiovascular disease (CVD) and early mortality in non-diabetic and diabetic patients. In 2005, the International Diabetes Federation (IDF) and the Examination Committee of Criteria for Diagnosis of Metabolic Syndrome in Japan published new definitions of metabolic syndrome in which central obesity was an indispensable factor. However, the significance of this new definition to CVD in type 2 diabetes has not yet been clarified. A cross-sectional study was conducted with 294 Japanese type 2 diabetic patients without known cardiovascular disease to evaluate the association between metabolic syndrome defined by this new definition and carotid atherosclerosis, and the significance of central obesity for the prediction of the development of carotid atherosclerosis. In a multivariate regression analysis, metabolic syndrome but not central obesity was significantly associated with carotid intima-media thickness (IMT) independent of known cardiovascular risk factors (p<0.05). In addition, whereas carotid IMT was significantly increased according to the increase in the number of components of metabolic syndrome, it was not significantly different between the groups with the same number of components of metabolic syndrome with or without central obesity. These findings suggest that the prediction of the development of carotid atherosclerosis in Japanese type 2 diabetic patients could be improved by the assessment of aggregation of components of metabolic syndrome rather than with or without metabolic syndrome by this new definition.

Laughter up-regulates the genes related to NK cell activity in diabetes.

To elucidate the sustainable effects of laughter on gene expression, we recruited type 2 diabetic patients who were in-patient for receiving self-management education and examined time-dependent regulation for gene expression by laughter. Two-day experiment was performed. On one day, the patients watched comic video and laughed together with hospital staffs. On the other day, they participated in an inpatient diabetes educational program. Blood samples were collected before and 1.5, 4 h after watching comic video or spending lecture time, and changes in gene expression were comprehensively analyzed by microarray technique. Of the 41,000 genes analyzed, the laughter relatively up-regulated 39 genes, among which, 27 genes were relatively increased in the expression for all the observation period after watching comic video. By functional classification of these genes, 14 genes were found to be related to natural killer cell activity. No genes were included that are directly involved in blood glucose regulation, though successive suppression of postprandial blood glucose levels was observed. These results suggest that the laughter influences the expression of many genes classified into immune responses, and may contribute to amelioration of postprandial blood glucose elevation through a modulation of NK cell activity caused by up-regulation of relating genes.

Prevention of diabetic nephropathy in rats by prostaglandin E receptor EP1-selective antagonist.

Local production of prostaglandins (PGs) in the kidney is increased in clinical and experimental diabetic nephropathy, but the role of PGs in the pathogenesis and progression of diabetic nephropathy has remained unclear. It is here shown that an orally active antagonist selective for the PGE receptor EP1 subtype potently prevents the progression of nephropathy in streptozotocin-induced diabetic rats. The effects are shown by ameliorated renal and glomerular hypertrophy, decreased mesangial expansion, inhibited transcriptional activation of transforming growth factor-beta (TGF-beta) and fibronectin, and complete suppression of proteinuria. In vitro, this agent completely inhibits TGF-beta and fibronectin upregulation in mesangial cells cultured under high-glucose conditions. These data indicate that the PGE2-EP1 system plays a crucial role in the development of diabetic renal injury in rats. It is further shown that both the EP1 antagonist and aspirin, a nonselective PG synthase inhibitor, markedly attenuate mesangial expansion, whereas only the EP1 antagonist inhibits glomerular hypertrophy and proteinuria, which suggests that these changes are caused by different mechanisms. This study reveals a potential usefulness of selective EP1 blockade as a novel therapeutic strategy for diabetic nephropathy and also brings a new insight into our understanding of this disease.

Ameliorated glomerular injury in mice overexpressing brain natriuretic peptide with renal ablation.

Brain natriuretic peptide (BNP) is a cardiac hormone produced by the ventricle, and its secretion is markedly increased in heart failure, hypertension, and renal failure. Transgenic mice that overexpress BNP in the liver (BNP-Tg) were recently generated, resulting in low BP. To elucidate the role of BNP in renal pathophysiology, the effect of chronic excess of BNP in transgenic mice on glomerular injury after subtotal nephrectomy induced by resection of the renal poles was examined. After nephrectomy, glomerular cross-sectional areas in control nontransgenic mice markedly increased as compared with those in sham-operated mice (+81 +/- 7%), whereas there was only a modest increase in BNP-Tg (+10 +/- 6%). Expansion of the mesangial area and increase in the intraglomerular cell number were also inhibited in BNP-Tg. Glomerular expressions of transforming growth factor-beta and fibronectin were increased with hypertrophy and were significantly suppressed in BNP-Tg. Furthermore, increases in the urinary albumin excretion and BP were significantly ameliorated in BNP-Tg. Chronic hydralazine treatment in nephrectomized nontransgenic mice failed to inhibit glomerular hypertrophy. These findings indicate that the chronic excess of BNP in mice ameliorates glomerular hypertrophy and mesangial expansion after renal ablation. The results also suggest that the observed effects of natriuretic peptides under reduced renal mass are not due merely to systemic BP reduction and may be therapeutically applicable in various renal diseases.