Lu Juming

The kidney expression of matrix metalloproteinase-9 in the diabetic nephropathy of Kkay mice

BACKGROUND Disorder of the extracellular matrix has been suggested to play a role in the development of diabetic nephropathy. The aim of the present study was to examine the expression of matrix metalloproteinase-9 (MMP-9) in the kidney of Kkay mice, a type 2 diabetic model. METHODS Eight Kkay control mice (KA) and eight Kkay diabetic mice (KB) were fed with the same diets for 4 months and sacrificed after glucose levels and weight were measured. The renal pathological changes were examined by periodic acid-Schiff and periodic acid-silver methenamine staining, and the glomerulosclerosis indexes (GIs) were calculated. The levels of MMP-9 protein in the kidney tissue were assessed by immunohistochemistry. The gene expression of MMP-9 was measured by reverse transcription polymerase chain reaction. RESULTS The diabetic group had morphological findings of diabetic nephropathy, and their GI (240.0+/-17.3) was much higher than that of the control group (118.4+/-15.1) (P<.01). The mean positive area of MMP-9 protein in the glomeruli of Kkay mice in the KB group was higher than that in the KA group. The expression of MMP-9 messenger RNA level in the diabetic KB group was up-regulated when compared with the KA group. CONCLUSION The expression of MMP-9 in the kidney of mice with diabetic nephropathy was enhanced, and MMP-9 might be involved in the development of diabetic nephropathy.

Effects of plasma homocysteine levels on serum HTase/PON activity in patients with type 2 diabetes

IntroductionHomocysteine is a predictor of vascular disease and may have an important role in diabetes. In this study, we examined the effects of folic acid and methylcobalamin supplementation on changes in homocysteine (Hcy) levels and homocysteine thiolactonase/paraoxonase (HTase/PON) activity in a short-term trial.MethodsNinety patients with type 2 diabetes were randomly divided into three groups: Group I received no vitamin supplementation, group II received 5 mg/day folic acid (orally), group III received folic acid (5 mg/day) in combination with methylcobalamin (500 μg/day; intramuscularly, on prescription). All patients were treated for 2 weeks. Plasma Hcy, HTase/PON activity, vitamin B12, and folic acid were measured before and after supplementation in each group. In addition, forty healthy (nondiabetic) controls were enrolled.ResultsSerum HTase/PON activity was significantly higher in diabetics compared with controls, plasma Hcy levels were significantly lower (P<0.05). After vitamin supplementation there was a significant reduction in plasma Hcy levels. The mean percentage reduction in Hcy was 2.75% in group I, 14% in group II and 37.3% in group III. There was a significant inverse correlation between the changes in HTase/PON activity and Hcy levels (r=−0.29, P=0.004). A 2.72% increase in HTase/PON activity was seen in group I, an 8.03% increase was detected when folic acid was given in group II (P<0.001), and a 17.59% increase in HTase/PON activity was seen in group III (P<0.001).ConclusionShort-term oral folic acid (5 mg/day) supplementation with or without methylcobalamin appeared to be an effective approach to decrease Hcy levels and increase HTase/PON activity in patients with type 2 diabetes. A decrease in plasma Hcy levels may partly account for the elevation of serum HTase/PON activity. This could be a novel mechanism to protect against vascular diabetic complications.

Effects of Nateglinide on Postprandial Plasma Glucose Excursion and Metabolism of Lipids in Chinese Patients with Type 2 Diabetes：A 4-week, randomized, active-control, open-label, parallel-group, multicenter trial.

Abstract Background and objective Both nateglinide and acarbose can decrease postprandial plasma glucose through different mode of action, therefore may improve oxidative stress and inflammation in patients with type 2 diabetes mellitus (T2DM). There is lack of comprehensive data on effects of nateglinide versus acarbose on plasma glucose level, lipid profiles and inflammatory response of postprandial status in drug naïve Chinese patients with T2DM, therefore we conducted a clinical trial to answer these questions. Methods In a 4-week, randomized, active-control, open-label, parallel-group, multicenter trial, 160 anti-diabetic drug-naïve T2DM patients were randomized to receive either nateglinide or acarbose for 4 weeks. Postprandial glucose profiles with postprandial glucose excursion (PPGE), postprandial lipids profile and the postprandial pro-inflammatory factor of high sensitivity C - reactive protein (hsCRP) were assessed in a standardized meal test. Results Both nateglinide and acarbose could reduce PPGE 2 h significantly (P<0.01) and the two drugs had comparable effects on reducing glycated albumin (-1.2+1.57% and -1.2+2.13%, P<0.01). Nateglinide markedly decreased free fatty acids (FFA) at postprandial 30, 60, 90 minute (P<0.05), however acarbose had no effect on FFA. Furthermore, acarbose decreased fasting HDL-C significantly (P<0.01). No significant effect on hsCRP was found in either group. The number of people experiencing adverse events was similar (nateglinide 13.8%, acarbose 18.8%, P=0.521) and there was low frequency of symptomatic hypoglycemia in both groups (nateglinide 5%, acarbose 1.3%). No confirmed hypoglycemia or serious hypoglycemia was observed. Several limitations in the present study include that we cannot exclude the effect of behavior change in the glycemic control through the study, and the number of subjects was relatively small. Conclusions Nateglinide and acarbose were similar in controlling the postprandial glucose in Chinese drug naïve patients with T2DM. In addition, nateglinide had better performance on improving lipids metabolism under postprandial status in comparison with acarbose. Overall, nateglinide had a safety profile similar to acarbose in this study.

Successful Laparoscope Resection of Ectopic Insulinoma in Duodenohepatic Ligament

Both ectopic pancreas and insulinoma are rare. A 21-year-old male patient had suffered from hypoglycemia episodes for 3 years and was diagnosed to have insulinoma based on biochemical and endocrinological evaluations. Various localization approaches revealed a distinct tumor outside the pancreas. With intraoperative endoscopy, the tumor in duodenohepatic ligament was identified and successfully resected. Pathologic evaluation revealed an ectopic insulinoma with ectopic pancreas. Therefore, when the biochemically confirmed insulinoma could not be well-definitely localized, the possibility of ectopic insulinoma should be suspected. In addition, radiography examinations and operation exploration should extend to the field where ectopic pancreas usually presents.

Effects of telmisartan on lipid metabolisms and proinflammatory factors secretion of differentiated 3T3-L1 adipocytes

Aim: To investigate the effect of telmisartan on the lipometabolisms and the proinflammatory factors secreted from 3T3-L1 adipocytes and to explore the possible mechanisms. Materials and methods: Telmisartan was applied to interfere with mature 3T3-L1 adipocytes. The culture’s free fatty acids, interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) were evaluated. Oil Red O staining was used to determine the adipogenesis of 3T3-L1 adipocytes. 18F-FDG uptake levels corrected for protein content were determined by cellular radioactivity. The total RNA was isolated for hybridization experimentation in the microarray. Results: Telmisartan reduced lipid storage and increased 18F-FDG uptake in a dose-dependent manner, reduced the levels of IL-6 and TNFα and increased those of free fatty acids. One hundred and fifty-seven differentially expressed genes were found by microarray. The mitogen-activated protein kinase (MAPK) signaling pathway involved in the secretion of proinflammatory factor and lipid metabolisms was affected by telmisartan. The expression of endothelial nitric oxide synthetase gene 3 (Nos3) and carnitine palmitoyl transferase 1α (CPT1α) was up-regulated by telmisartan. Conclusions: Telmisartan affected lipometabolisms and the proinflammatory factors secreted from adipocytes. Nos3, CPT1α and the MAPK pathway being affected by telmisartan may be the underlying cause of the improvement in lipid metabolisms and secretion of proinflammatory factors of differentiated 3T3-L1 adipocytes.