Reverse-translational identification of a cerebellar satiation network.

The brain is the seat of body weight homeostasis. However, our inability to control the increasing prevalence of obesity highlights a need to look beyond canonical feeding pathways to broaden our understanding of body weight control1-3. Here we used a reverse-translational approach to identify and anatomically, molecularly and functionally characterize a neural ensemble that promotes satiation. Unbiased, task-based functional magnetic resonance imaging revealed marked differences in cerebellar responses to food in people with a genetic disorder characterized by insatiable appetite. Transcriptomic analyses in mice revealed molecularly and topographically -distinct neurons in the anterior deep cerebellar nuclei (aDCN) that are activated by feeding or nutrient infusion in the gut. Selective activation of aDCN neurons substantially decreased food intake by reducing meal size without compensatory changes to metabolic rate. We found that aDCN activity terminates food intake by increasing striatal dopamine levels and attenuating the phasic dopamine response to subsequent food consumption. Our study defines a conserved satiation centre that may represent a novel therapeutic target for the management of excessive eating, and underscores the utility of a 'bedside-to-bench' approach for the identification of neural circuits that influence behaviour.

Efficacy of insulin glargine in perioperative glucose control in type 2 diabetic patients.

BACKGROUND AND OBJECTIVE: Insulin glargine as a basal insulin exhibits constant absorption with no pronounced peaks in blood insulin levels and 24-h duration of action. We checked the effect of insulin glargine through the comparison of insulin glargine with glucose-insulin-potassium (GIK) on perioperative glucose control in insulin-treated type 2 diabetic patients. METHODS: Thirty insulin-treated type 2 diabetic patients, 40-80 years of age, were subjected to femoral artery bypass or knee amputation under general anaesthesia. The insulin glargine group (n = 15) was treated with insulin glargine (two-thirds of the total daily insulin dose required) subcutaneous administration with 5% dextrose solution infusion. The GIK group (n = 15) was treated with GIK infusion (125 ml h). Blood glucose levels were checked every 30 min during anaesthesia and 1 h after extubation. Potassium was checked every 1 h during anaesthesia and 2-4 h after extubation. Statistical analysis was performed with unpaired t test. RESULTS: There were no significant differences in the time course of blood glucose levels during operation and postoperative period between the two groups (P < 0.05). There was no hypoglycaemic episode in the perioperative period and no significant differences in potassium levels between the two groups. CONCLUSION: Insulin glargine was as effective as GIK regimen for perioperative glycaemic control during major surgery in insulin-dependent type 2 diabetic patients.

Comparison of Methods for Determining ABO Blood Type in Cynomolgus Macaques (Macaca fascicularis).

Thorough examination of ABO blood type in cynomolgus monkeys is an essential experimental step to prevent humoral rejection during transplantation research. In the present study, we evaluated current methods of ABO blood-antigen typing in cynomolgus monkeys by comparing the outcomes obtained by reverse hemagglutination, single-nucleotide polymorphism (SNP) analysis, and buccal mucosal immunohistochemistry. Among 21 animals, 5 were type A regardless of the method. However, of 8 serologically type B animals, 3 had a heterozygous type AB SNP profile, among which 2 failed to express A antigen, as shown by immunohistochemical analysis. Among 8 serologically type AB animals, 2 appeared to be type A by SNP analysis and immunohistochemistry. None of the methods identified any type O subjects. We conclude that the expression of ABO blood-group antigens is regulated by an incompletely understood process and that using both SNP and immunohistochemistry might minimize the risk of incorrect results obtained from the conventional hemagglutination assay.