Taurine supplementation enhances nutrient-induced insulin secretion in pancreatic mice islets.

BACKGROUND: Taurine (TAU), a naturally occurring sulfur-containing amino acid, is found at high concentrations in plasma and mammalian tissues and regulates osmolarity, ion channel activity, and glucose homeostasis. Several reports have shown that physiological plasma TAU levels seem to be important for adequate beta (beta)-cell function and insulin action, since low concentrations of TAU in the plasma have been reported in the pre-diabetic and diabetic states. METHODS: Glucose tolerance and insulin sensitivity were investigated in mice supplemented with 2% (w/v) TAU in their drinking water for 30 days, as well as the insulin secretion from isolated islets stimulated by glucose or L-leucine. RESULTS: TAU-supplemented mice demonstrated improved glucose tolerance and higher insulin sensitivity, compared to controls (CTL). In addition, their islets secreted more insulin in response to high concentrations of glucose and L-leucine. L-[U-(14)C]leucine oxidation was higher in TAU than in CTL islets, whereas D-[U-(14)C]glucose oxidation, ATP levels, glucose transporter (GLUT) 2 and glucokinase (GCK) protein expressions were similar in both types of islets. The L-type beta(2) subunit voltage-sensitive Ca(2+) channel protein, as well as (45)Ca uptake, were significantly higher in TAU-supplemented than CTL islets. In addition, islets from TAU-supplemented mice secreted more glucagon than CTL islets at low glucose. CONCLUSIONS: TAU supplementation improves glucose tolerance and insulin sensitivity in mice, as well as insulin secretion from isolated islets. The latter effect seems to be, at least in part, dependent on a better Ca(2+) handling by the islets.

Central exercise action increases the AMPK and mTOR response to leptin.

AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR) are key regulators of cellular energy balance and of the effects of leptin on food intake. Acute exercise is associated with increased sensitivity to the effects of leptin on food intake in an IL-6-dependent manner. To determine whether exercise ameliorates the AMPK and mTOR response to leptin in the hypothalamus in an IL-6-dependent manner, rats performed two 3-h exercise bouts, separated by one 45-min rest period. Intracerebroventricular IL-6 infusion reduced food intake and pretreatment with AMPK activators and mTOR inhibitor prevented IL-6-induced anorexia. Activators of AMPK and fasting increased food intake in control rats to a greater extent than that observed in exercised ones, whereas inhibitor of AMPK had the opposite effect. Furthermore, the reduction of AMPK and ACC phosphorylation and increase in phosphorylation of proteins involved in mTOR signal transduction, observed in the hypothalamus after leptin infusion, were more pronounced in both lean and diet-induced obesity rats after acute exercise. Treatment with leptin reduced food intake in exercised rats that were pretreated with vehicle, although no increase in responsiveness to leptin-induced anorexia after pretreatment with anti-IL6 antibody, AICAR or Rapamycin was detected. Thus, the effects of leptin on the AMPK/mTOR pathway, potentiated by acute exercise, may contribute to appetite suppressive actions in the hypothalamus.

A central role for neuronal AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in high-protein diet-induced weight loss.

OBJECTIVE: A high-protein diet (HPD) is known to promote the reduction of body fat, but the mechanisms underlying this change are unclear. AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) function as majors regulators of cellular metabolism that respond to changes in energy status, and recent data demonstrated that they also play a critical role in systemic energy balance. Here, we sought to determine whether the response of the AMPK and mTOR pathways could contribute to the molecular effects of an HPD. RESEARCH DESIGN AND METHODS: Western blotting, confocal microscopy, chromatography, light microscopy, and RT-PCR assays were combined to explore the anorexigenic effects of an HPD. RESULTS: An HPD reduced food intake and induced weight loss in both normal rats and ob/ob mice. The intracerebroventricular administration of leucine reduced food intake, and the magnitude of weight loss and reduction of food intake in a leucine-supplemented diet are similar to that achieved by HPD in normal rats and in ob/ob mice, suggesting that leucine is a major component of the effects of an HPD. Leucine and HPD decrease AMPK and increase mTOR activity in the hypothalamus, leading to inhibition of neuropeptide Y and stimulation of pro-opiomelanocortin expression. Consistent with a cross-regulation between AMPK and mTOR to control food intake, our data show that the activation of these enzymes occurs in the same specific neuronal subtypes. CONCLUSIONS: These findings provide support for the hypothesis that AMPK and mTOR interact in the hypothalamus to regulate feeding during HPD in a leucine-dependent manner.