Nutrient Sensor mTORC1 Regulates Insulin Secretion by Modulating ß-Cell Autophagy.

The dynamic regulation of autophagy in ß-cells by cycles of fasting-feeding and its effects on insulin secretion are unknown. In ß-cells, mechanistic target of rapamycin complex 1 (mTORC1) is inhibited while fasting and is rapidly stimulated during refeeding by a single amino acid, leucine, and glucose. Stimulation of mTORC1 by nutrients inhibited the autophagy initiator ULK1 and the transcription factor TFEB, thereby preventing autophagy when ß-cells were continuously exposed to nutrients. Inhibition of mTORC1 by Raptor knockout mimicked the effects of fasting and stimulated autophagy while inhibiting insulin secretion, whereas moderate inhibition of autophagy under these conditions rescued insulin secretion. These results show that mTORC1 regulates insulin secretion through modulation of autophagy under different nutritional situations. In the fasting state, autophagy is regulated in an mTORC1-dependent manner, and its stimulation is required to keep insulin levels low, thereby preventing hypoglycemia. Reciprocally, stimulation of mTORC1 by elevated leucine and glucose, which is common in obesity, may promote hyperinsulinemia by inhibiting autophagy.

Is It Me or My Hormones? Neuroendocrine Activation Profiles to Visual Food Stimuli Across the Menstrual Cycle.

Context: Homeostatic energy balance is controlled via the hypothalamus, whereas regions controlling reward and cognitive decision-making are critical for hedonic eating. Eating varies across the menstrual cycle peaking at the midluteal phase. Objective: To test responses of females with regular cycles during midfollicular and midluteal phase and of users of monophasic oral contraception pills (OCPs) to visual food cues. Design: Participants performed a functional magnetic resonance imaging while exposed to visual food cues in four time points: fasting and fed conditions in midfollicular and midluteal phases. Patients: Twenty females with regular cycles and 12 on monophasic OCP, aged 18 to 35 years. Main Outcome Measures: Activity in homeostatic (hypothalamus), reward (amygdala, putamen and insula), frontal (anterior cingulate cortex, dorsolateral prefrontal cortex), and visual regions (calcarine and lateral occipital cortex). Setting: Tertiary hospital. Results: In females with regular cycles, brain regions associated with homeostasis but also the reward system, executive frontal areas, and afferent visual areas were activated to a greater degree during the luteal compared with the follicular phase. Within the visual areas, a dual effect of hormonal and prandial state was seen. In females on monophasic OCPs, characterized by a permanently elevated progesterone concentration, activity reminiscent of the luteal phase was found. Androgen, cortisol, testosterone, and insulin levels were significantly correlated with reward and visual region activation. Conclusions: Hormonal mechanisms affect the responses of women's homeostatic, emotional, and attentional brain regions to food cues. The relation of these findings to eating behavior throughout the cycle needs further investigation.

An outbreak of new, nonmultidrug-resistant, methicillin-resistant Staphylococcus aureus strain (sccmec type iiia variant-1) in the neonatal intensive care unit transmitted by a staff member.

A methicillin-resistant Staphylococcus aureus (MRSA) strain was recovered in a neonatal intensive care unit from 3 blood and 3 sputum specimens with antibiotic susceptibility profile characteristic of community-acquired MRSA. Epidemiologic survey resulted in isolation of an identical strain from the nares of one nurse. All isolates carried a new SCCmec type IIIA variant. Treatment of the nurse with topical mupirocin resulted in cessation of the outbreak.