This study explored the effects of taste and oral anaesthesia on human sequential swallowing. Subjects were healthy adults (n = 42, mean age 28 years, 21 females), investigated by means of a water swallow test. Taste stimuli comprised quinine, glucose, citrus and saline solutions compared with neutral water. Oral anaesthesia comprised topical lidocaine at doses of 10, 20 and 40 mg and compared with placebo. Data were collected on swallowing speed (volume per second), inter-swallow interval and swallowing capacity (volume per swallow). Compared with water, glucose, citrus and saline reduced swallowing speed (10.94 +/- 0.89 versus 9.56 +/- 0.79, 9.33 +/- 1.19, 9.37 +/- 0.92 ml/s respectively, P < 0.05). Inter-swallow interval was increased only by quinine and saline (1.47 +/- 1.11 versus 2.13 +/- 0.34 and 1.92 +/- 0.31 s, P < 0.04). Swallowing capacity was only marginally increased by quinine (P = 0.0759). Compared with the placebo, only 40 mg of lidocaine altered swallowing, immediately reducing the swallowing speed (7.89 +/- 2.34 versus 10.11 +/- 3.26 ml/s, P < 0.05) and increasing inter-swallow interval (1.67 +/- 0.38 versus 1.45 +/- 0.29 s, P < 0.01) without affecting capacity. By 15 min all measures except sensory thresholds had returned to baseline values. Thus, swallowing function is highly influenced by chemosensory input, providing insight into how oral sensation regulates pharyngeal swallowing.

The ability to maintain skeletal muscle mass appears to be impaired in insulin resistant conditions. The present study investigated the effect of lipid induced insulin resistance on the rate of muscle protein synthesis. Seven healthy male volunteers (23 ± 1 y, 24 ± 1 kg/m2) underwent a 7 h intravenous infusion of [ring‐2H5]phenylalanine (0.5 mg/kg/h) on two randomised occasions combined with either 0.9% saline or 10% Intralipid (100 mL/h; Fresenius Kabi, Germany). After a 4 h ‘basal’ period, a 21 g bolus of amino acids (except phenylalanine and tyrosine) was administered in a 440 mL solution nasogastrically, and a 3 h euglycaemic (4.5 mmol/L) hyperinsulinemic (50 mU/m2/min) clamp was commenced (‘fed’ period). Muscle biopsies were obtained from the vastus lateralis at 1.5, 4, and 7 h. Lipid infusion resulted in elevated levels of plasma free fatty acids when compared to saline (P<0.001), which reduced fed glucose disposal by 20% (P<0.01) and pyruvate dehydrogenase complex activation by 50% (P<0.05). Furthermore, whereas mixed muscle fractional synthetic rate increased from the basal to fed period during saline infusion (0.040 ± 0.010 to 0.067 ± 0.013 %/h; P<0.05), it did not respond during lipid infusion (0.048 ± 0.013 to 0.038 ± 0.005 %/h), despite the same circulating insulin and leucine concentrations. Thus, lipid induced insulin resistance results in anabolic resistance to amino acid ingestion in healthy young men.

Insulin resistance is closely related to intramyocellular lipid (IMCL) accumulation, and both are associated with increasing age. It remains to be determined to what extent perturbations in IMCL metabolism are related to the aging process per se. On two separate occasions, whole-body and muscle insulin sensitivity (euglycemichyperinsulinemic clamp with 2-deoxyglucose) and fat utilization during 1 h of exercise at 50% VO 2max ([U-13 C]palmitate infusion combined with electron microscopy of IMCL) were determined in young lean (YL), old lean (OL), and old overweight (OO) males. OL displayed IMCL content and insulin sensitivity comparable with those in YL, whereas OO were markedly insulin resistant and had more than twofold greater IMCL in the subsarcolemmal (SSL) region. Indeed, whereas the plasma free fatty acid R a and R d were twice those of YL in both OL and OO, SSL area only increased during exercise in OO. Thus, skeletal muscle insulin resistance and lipid accumulation often observed in older individuals are likely due to lifestyle factors rather than inherent aging of skeletal muscle as usually reported. However, age per se appears to cause exacerbated adipose tissue lipolysis, suggesting that strategies to reduce muscle lipid delivery and improve adipose tissue function may be warranted in older overweight individuals.The global prevalence of type 2 diabetes is most apparent in older people (1), and it is estimated that the number of people over 65 years of age with diabetes will have increased 4.5-fold by 2050 (2). Gaining mechanistic insight into age-related insulin resistance and strategies to improve insulin sensitivity with age are clearly warranted. Although aging is associated with insulin resistance, age per se does not appear to cause insulin resistance (3-5). Several factors that likely contribute to age-related insulin resistance include increased abdominal adiposity and reduced physical activity (3,4), along with declines in muscle mass (6,7). Of note, intramyocellular lipid (IMCL) accumulates with age, particularly in subsarcolemmal (SSL) regions (8), and has been strongly associated with insulin resistance (9-12). Indeed, SSL lipid accumulation has been linked to the accumulation of metabolites, such as diacylglycerol (DAG) and ceramide, thought by some (13-15), but not others (16), to contribute to impaired insulinstimulated muscle glucose uptake. Nevertheless, it remains contentious as to which factors associated with age influence IMCL accumulation.The accumulation of IMCL and associated metabolites likely results from an imbalance between muscle lipid delivery and oxidation. Indeed, studies have demonstrated reduced free fatty acid (FFA) oxidation in older people compared with young, despite whole-body lipolysis and plasma FFA availability being greater at rest and during exercise at the same absolute and relative intensities (17,18). Linked to this, several studies have suggested that age-related blunting of FFA oxidation and increased IMCL accumulation are a result of reduced