Systemic Glucoregulation by Glucose-Sensing Neurons in the Ventromedial Hypothalamic Nucleus (VMH).

The ventromedial hypothalamic nucleus (VMH) regulates glucose production in the liver as well as glucose uptake and utilization in peripheral tissues, including skeletal muscle and brown adipose tissue, via efferent sympathetic innervation and neuroendocrine mechanisms. The action of leptin on VMH neurons also increases glucose uptake in specific peripheral tissues through the sympathetic nervous system, with improved insulin sensitivity. On the other hand, subsets of VMH neurons, such as those that express steroidogenic factor 1 (SF1), sense changes in the ambient glucose concentration and are characterized as glucose-excited (GE) and glucose-inhibited (GI) neurons whose action potential frequency increases and decreases, respectively, as glucose levels rise. However, how these glucose-sensing (GE and GI) neurons in the VMH contribute to systemic glucoregulation remains poorly understood. In this review, we provide historical background and discuss recent advances related to glucoregulation by VMH neurons. In particular, the article describes the role of GE neurons in the control of peripheral glucose utilization and insulin sensitivity, which depend on mitochondrial uncoupling protein 2 of the neurons, as well as that of GI neurons in the control of hepatic glucose production through hypoglycemia-induced counterregulatory mechanisms.

[Complete response of primary tumor in a case of advanced gastric cancer with liver metastasis treated by TS-1 plus divided administration of CDDP].

A 62-year-old female patient was hospitalized for general fatigue and appetite loss. Type 3 gastric cancer (moderate differentiated adenocarcinoma) with liver metastasis (S8) and direct invasion to the retro-peritoneal space and duodenal third portion was detected by endoscopic and radiographic examination. This case was judged to be unresectable from these findings. TS-1 plus divided administration of CDDP was performed. TS-1 (100 mg/day) was administrated from day 1 to 21 followed by 14 days rest as one course. CDDP (20 mg/m2) was infused for 2 hours on day 1, 8, and 15. One course was done in the hospital, and the following 2 courses as ambulatory treatment. Grade 2 neutropenia was observed as an adverse reaction. At the completion of 3 courses, partial response in the primary tumor, complete response in the duodenal third portion and no change in the liver metastasis were assessed by examination. Because of this remarkable down-staging, distal gastrectomy and radiofrequency ablation (RFA) for liver metastasis were performed. There was no evidence of direct invasion to the other organs from the primary tumor in intraoperative findings. Pathological examination revealed the disappearance of carcinoma cell in the resected stomach and the surrounding lymphnodes. In conclusion, this chemotherapy regimen has an excellent antitumor effect with low toxicities. Therefore, this regimen was comparatively safe for outpatients and was an effective neo-adjuvant chemotherapy.

Joint effects of Chlamydia pneumoniae infection and classic coronary risk factors on risk of acute myocardial infarction.

BACKGROUND: Although not in itself strongly predictive of coronary heart disease, Chlamydia pneumoniae infection could interact with classic risk factors in determining risk of acute myocardial infarction (AMI). METHODS: We assessed C pneumoniae immunoglobulin (Ig) G and IgA titers and classic risk factors in 618 patients with AMI and in 967 controls. RESULTS: IgG titers were not related to AMI, but a significant association was seen between IgA titers and AMI. Excess risk of AMI was noted mainly among patients with the highest IgA titers, such as those beyond 2.88 (the 95th percentile cutoff point in control subjects), showing a 1.8-fold increase in risk (odds ratio 1.75, 95% CI 1.04-2.92). Classic risk factors did not differ between subjects with IgA titers above and below the 95th percentile cutoff. However, in multivariate analyses, models incorporating both IgA titers and a classic risk factor such as obesity, hypercholesterolemia, or smoking predicted risk more effectively than single-parameter models. For example, the odds ratio for AMI among subjects with the highest IgA titers plus hypercholesterolemia was greater than the product of individual risks associated with these high IgA titers and with hypercholesterolemia. CONCLUSIONS: Interactions with classic risk factors (ie, obesity, hypercholesterolemia, and smoking), increased the predictive value of C pneumoniae IgA antibody titers in determining risk of AMI.

Thyroid hormone augments GLUT4 expression and insulin-sensitive glucose transport system in differentiating rat brown adipocytes in culture.

The effects of triiodothyronine (T3) on differentiation-dependent expression of GLUT and responses of glucose transport to insulin and norepinephrine (NE) were investigated. Precursor cells of brown adipocytes isolated from the interscapular brown adipose tissue of newborn rats were cultured in the absence or presence of various concentrations of T3. Western bolt analysis revealed that treatment with T3 resulted in an increased expression of GLUT4, in a dose-dependent manner, whereas GLUT1 contents were unchanged. In parallel with the increase in GLUT4 expression, T3 improved insulin sensitivity for glucose transport, being accompanied by an increase in maximal transport rate and a reduction of ED(50). In contrast, T3-treatment of the brown adipocytes during the differentiation process had little effect on NE-regulatable glucose transport system. These results suggest that T3 plays a predominant role in the development of insulin-sensitive glucose transport during differentiation of brown adipocytes.