Unlike the adjustable gastric banding procedure (AGB), Roux-en-Y gastric bypass surgery (RYGBP) in humans has an intriguing effect: a rapid and substantial control of type 2 diabetes mellitus (T2DM). We performed gastric lap-band (GLB) and entero-gastro anastomosis (EGA) procedures in C57Bl6 mice that were fed a high-fat diet. The EGA procedure specifically reduced food intake and increased insulin sensitivity as measured by endogenous glucose production. Intestinal gluconeogenesis increased after the EGA procedure, but not after gastric banding. All EGA effects were abolished in GLUT-2 knockout mice and in mice with portal vein denervation. We thus provide mechanistic evidence that the beneficial effects of the EGA procedure on food intake and glucose homeostasis involve intestinal gluconeogenesis and its detection via a GLUT-2 and hepatoportal sensor pathway.

The ability for the brain to sense peripheral fuel availability is mainly accomplished within the hypothalamus, which detects ongoing systemic nutrients and adjusts food intake and peripheral metabolism as needed. Here, we hypothesized that mitochondrial reactive oxygen species (ROS) could trigger sensing of nutrients within the hypothalamus. For this purpose, we induced acute hypertriglyceridemia in rats and examined the function of mitochondria in the hypothalamus. Hypertriglyceridemia led to a rapid increase in the mitochondrial respiration in the ventral hypothalamus together with a transient production of ROS. Cerebral inhibition of fatty acids-CoA mitochondrial uptake prevented the hypertriglyceridemia-stimulated ROS production, indicating that ROS derived from mitochondrial metabolism. The hypertriglyceridemia-stimulated ROS production was associated with change in the intracellular redox state without any noxious cytotoxic effects, suggesting that ROS function acutely as signaling molecules. Moreover, cerebral inhibition of hypertriglyceridemia-stimulated ROS production fully abolished the satiety related to the hypertriglyceridemia, suggesting that hypothalamic ROS production was required to restrain food intake during hypertriglyceridemia. Finally, we found that fasting disrupted the hypertriglyceridemia-stimulated ROS production, indicating that the redox mechanism of brain nutrient sensing could be modulated under physiological conditions. Altogether, these findings support the role of mitochondrial ROS as molecular actors implied in brain nutrient sensing. Diabetes 56: 152-160, 2007T he long-term maintenance of the body's energy homeostasis is a complex biological process achieved by numerous complementary mechanisms that imply sensor systems of fuel availability located in both peripheral and central sites. The hypothalamus in the central nervous system is a primary site of integration of nutritional information, which includes neural inputs as well as circulating metabolic signals, i.e., glucose or fatty acids (1,2). In turn, the hypothalamus elicits appropriate behavioral and metabolic responses to counterbalance any changes in the energy status.Previous studies have already shown that an overload of systemic lipids could stimulate activity of specific hypothalamic neurons (3) and modulate expression of neuropeptides, the key effectors of the hypothalamus (3-6), which leads to rapid or more delayed changes in peripheral metabolism. Moreover, chronic elevation of lipids may alter the hepatic sensitivity to insulin through their direct effect on the central nervous system (7). Recent findings (8) indicate that circulating lipids can directly act as signaling molecules, informing the hypothalamus about the body's metabolic status. Accordingly, it has been shown (9) that intracerebroventricular administration of long-chain fatty acids inhibited food intake and stimulated peripheral energy storage.One of the current challenges is to define the way fatty acids control neural activity within the hypotha...

Objectives Hypoglycorrhachia, or a low glucose level in the cerebrospinal fluid (CSF), can suggest bacterial, fungal, or tuberculous meningitis. When tests for these common infectious etiologies are negative, many clinicians are unsure of which diagnoses to consider, resulting in delayed treatment. We analyzed the diagnoses associated with hypoglycorrhachia to determine their relative frequencies at our institution, as well as summarizing all the diagnoses associated with hypoglycorrhachia in the literature. Methods Retrospective analysis of adults with hypoglycorrhachia at a tertiary care teaching hospital over a 5 year period. Inclusion criteria included CSF glucose <40 mg/dL and age ≥ 18 years old. Exclusion criteria included CSF/serum glucose ≥ 0.6. Results 89 unique hypoglycorrhachia episodes were identified. The most common etiologies amongst all episodes of hypoglycorrhachia were bacterial meningitis (24%), fungal meningitis (15%), stroke/bleeds (13%), malignancy (11%), viral meningitis (6%), neurosarcoidosis (4%), neurosyphilis (4%), and cerebral toxoplasmosis (3%). The most common etiology was fungal meningitis (38%) among HIV–infected patients, and bacterial meningitis (62%) among neurosurgery patients. However, in patients without HIV or neurosurgical history, noninfectious etiologies (stroke/bleed (24%) and malignancy (22%)) were most common. Conclusions Many diagnoses, both infectious and noninfectious, lead to hypoglycorrhachia and must be considered in the differential diagnosis.

A 60% reduction in the standard IPV dose without reduction in antibody titers is possible through intradermal administration.