Upregulation of ICAM-1 in diabetic rats after transient forebrain ischemia and reperfusion injury.

BACKGROUND: Hyperglycemia exacerbates brain damage caused by cerebral ischemia. Neuroinflammation may play a role in mediating such enhanced damage. The objectives of this study were to examine the mRNA and protein levels and cell type distribution of ICAM-1 after cerebral ischemia in normo-and diabetic hyperglycemic rats. RESULTS: Compared to normoglycemic ischemia animals, diabetes aggravated neuronal death, decreased Nissl body staining, and increased ICAM-1 mRNA and protein levels in the frontal cortex. The increased ICAM-1 was located not only in vascular endothelial cells but also in cortical neurons. CONCLUSIONS: Our results suggest that exacerbated neuro-inflammation in the brain may mediate the detrimental effects of diabetes on the ischemic brain.

Comparison of a multiple daily insulin injection regimen (glargine or detemir once daily plus prandial insulin aspart) and continuous subcutaneous insulin infusion (aspart) in short-term intensive insulin therapy for poorly controlled type 2 diabetes patients.

Aims. To examine the potential differences between multiple daily injection (MDI) regimens based on new long-acting insulin analogues (glargine or detemir) plus prandial insulin aspart and continuous subcutaneous insulin aspart infusion (CSII) in patients with poorly controlled type 2 diabetes. Methods. Patients (n = 119) with poorly controlled type 2 diabetes of a duration exceeding five years were randomly assigned into three groups: Group A treated with CSII using insulin aspart; Group B treated with glargine-based MDI and Group C treated with detemir-based MDI. Results. Good glycemic control was achieved by patients in Group A in a significantly shorter duration than patients in Groups B and C. Total daily insulin, basal insulin dose and dose per kg body weight in Group A were significantly less than those in Groups B and C. Daily blood glucose fluctuation in Group A was significantly less than that in Groups B and C. There were no differences between Groups B and C. Conclusions. Aspart-based CSII may achieve good blood glucose control with less insulin doses over a shorter period compared with glargine or detemir-based MDI. No differences between glargine- and detemir-based MDI were detected in poorly controlled subjects with type 2 diabetes.

Nonalcoholic fatty liver disease and microvascular complications in type 2 diabetes.

AIM: To evaluate the correlation between nonalcoholic fatty liver disease (NAFLD) and microvascular complications in type 2 diabetes mellitus (T2DM). METHODS: Data were obtained from 1217 inpatients with T2DM (757 females, 460 males; aged 63.39 ± 12.28 years). NAFLD was diagnosed by hepatic ultrasonography. Diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR) were diagnosed according to their respective criteria. The prevalence of NAFLD and the independent correlations of clinical characteristics with NAFLD were determined by cross-tabulation and logistic regression, respectively. RESULTS: Approximately 61% of inpatients with T2DM in Qingdao, China had NAFLD, which decreased significantly with increase in age and prolonged course of diabetes. The prevalence of NAFLD in patients presenting with DN, DPN and DR was 49.4%, 57.2% and 54.9%, respectively. These rates were significantly lower than those of patients without DN, DPN and DR (65.9%, 65.6% and 66.1%, respectively, P < 0.05). Participants with NAFLD had greater body weight, waist circumference (WC), body mass index (BMI), fasting blood glucose (FBG), hemoglobin A1c, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, blood pressure, as well as triglyceride (TG) levels and lower high-density lipoprotein (HDL) concentration than those without NAFLD (P < 0.05). NAFLD was positively correlated with BMI, WC, TG, FBG, diastolic blood pressure, and systolic blood pressure but negatively correlated with the duration of diabetes, DR, DPN, DN, and HDL. CONCLUSION: Despite the benign nature of NAFLD, efforts should be directed toward early diagnosis, intensive blood glucose and blood pressure control, and effective dyslipidemia correction.

The effect of metformin on food intake and its potential role in hypothalamic regulation in obese diabetic rats.

Metformin appears to be involved in altering energy expenditure and thermogenesis, and could affect hypothalamic feeding circuits. However, it is not clear whether metformin is able to cross the blood-brain barrier (BBB) to reach the hypothalamus and exert a direct effect on the central nervous system. Here we show the presence of metformin in cerebrospinal fluid (CSF) of diabetic rats administered orally with metformin which was confirmed by detecting the concentration of metformin with liquid chromatography-tandem mass spectrometry. Food intake of diabetic rats treated with metformin was reduced, and glucose homeostasis was gained. Expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased in the hypothalamus of metformin-treated diabetic rats, though anorexigenic peptides pro-opiomelanocortin (POMC) did not change significantly. The phosphorylation of signal transducer and activator of transcription 3 (STAT3) was increased but phosphorylated AMP-activated kinase (AMPK) was similar in the hypothalamus of metformin-treated diabetic rats. Our findings suggest that metformin may cross BBB and play a central mechanism on regulation of food intake in the hypothalamus. The anorexic effect of metformin may be mediated by inhibition of NPY and AgRP gene expression through the STAT3 signaling pathway.

[Relationship between plasma level of leptin and the expression of leptin receptor in human adrenal tissues and tumors].

OBJECTIVE: To compare the mRNA, protein expression of long leptin receptor (Ob-Rb) in human adrenal tissues and tumors and observe the plasma level of leptin in primary aldosteronism (PA), cortisol-secreting tumors (CS) and pheochromocytomas (PHEO). METHODS: Total RNA and protein were extracted from 6 normal human adrenal glands, 10 CS, 20 PHEO; and 14 aldosterone-producing adenomas (APA) (RNA), 10 APA (protein); plasma samples were drawn from 20 controls, 15 PHEO, 29 PA and 11 CS. RESULTS: The mRNA and protein of Ob-Rb were widely expressed in human adrenal glands and tumors. The mRNA (0.32±0.12) and protein (1.31±0.26) expressions of Ob-Rb were higher in normal human adrenal cortex (C) than all other tissues (P<0.05) while the mRNA expression of Ob-Rb in APA (0.15±0.10) was higher than CS (0.05±0.02) (P<0.05). The mRNA expression of Ob-Rb in APA was positively correlated with plasma supine aldosterone level (r=0.670, P=0.024). The mRNA expression of Ob-Rb in CS was positively correlated with 24-hour urinary free cortisol level (r=0.870, P=0.005). The plasma level of leptin was higher in CS than in non-CS groups (P=0.001). CONCLUSIONS: Ob-Rb is widely expressed in adrenal tissues and tumors. There is a differential expression in various tissues. Further studies are warranted to understand the relationship between leptin and adrenal gland.

Bilateral pheochromocytoma as first presentation of von Hippel-Lindau disease in a Chinese family.

OBJECTIVE: To investigate the clinical and genetic features of a Chinese family with von Hippel-Lindau (VHL) disease revealed by bilateral pheochromocytoma. METHODS: The proband and other members in a Chinese family with familial pheochromocytoma were clinically evaluated and followed up. Genomic DNA extracted from the peripheral blood of 8 family members (including 3 patients) was amplified by polymerase chain reaction (PCR) and the PCR products were directly sequenced. RESULTS: The first presentation in the proband, his mother, and his sister was bilateral pheochromocytoma, and the missense mutation of 695G-A (Arg161Gln) in exon 3 of VHL gene was detected in the three patients. In the follow-up study, the proband and his mother were found to have other VHL tumors, induding retinal and cerebellar hemangioblastomas and pancreatic tumor. Neither clinical presentation of VHL disease nor gene mutation was found in other family members. CONCLUSION: VHL disease should be suspected in some patients with familial pheochromocytoma, and VHL gene screening helps to achieve early diagnosis of the disease.