High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine.

We determined the effect of coingestion of caffeine (Caff) with carbohydrate (CHO) on rates of muscle glycogen resynthesis during recovery from exhaustive exercise in seven trained subjects who completed two experimental trials in a randomized, double-blind crossover design. The evening before an experiment subjects performed intermittent exhaustive cycling and then consumed a low-CHO meal. The next morning subjects rode until volitional fatigue. On completion of this ride subjects consumed either CHO [4 g/kg body mass (BM)] or the same amount of CHO + Caff (8 mg/kg BM) during 4 h of passive recovery. Muscle biopsies and blood samples were taken at regular intervals throughout recovery. Muscle glycogen levels were similar at exhaustion [ approximately 75 mmol/kg dry wt (dw)] and increased by a similar amount ( approximately 80%) after 1 h of recovery (133 +/- 37.8 vs. 149 +/- 48 mmol/kg dw for CHO and Caff, respectively). After 4 h of recovery Caff resulted in higher glycogen accumulation (313 +/- 69 vs. 234 +/- 50 mmol/kg dw, P < 0.001). Accordingly, the overall rate of resynthesis for the 4-h recovery period was 66% higher in Caff compared with CHO (57.7 +/- 18.5 vs. 38.0 +/- 7.7 mmol x kg dw(-1) x h(-1), P < 0.05). After 1 h of recovery plasma Caff levels had increased to 31 +/- 11 microM (P < 0.001) and at the end of the recovery reached 77 +/- 11 microM (P < 0.001) with Caff. Phosphorylation of CaMK(Thr286) was similar after exercise and after 1 h of recovery, but after 4 h CaMK(Thr286) phosphorylation was higher in Caff than CHO (P < 0.05). Phosphorylation of AMP-activated protein kinase (AMPK)(Thr172) and Akt(Ser473) was similar for both treatments at all time points. We provide the first evidence that in trained subjects coingestion of large amounts of Caff (8 mg/kg BM) with CHO has an additive effect on rates of postexercise muscle glycogen accumulation compared with consumption of CHO alone.     

Effect of near physiologic insulin therapy on hypoglycemia counterregulation in type-1 diabetes

OBJECTIVES: The aim of this study was to examine hormonal counterregulation during insulin-induced hypoglycemia in type-1 diabetic patients during long-term near normoglycemic insulin therapy and intensive clinical care. METHODS: Type-1 diabetic patients (age 35.3 +/- 2 years, body mass index 22.8 +/- 1 kg x m(-2), mean diabetes duration 13.6 (11-17 years), mean HbA1c during the last year 6.6 +/- 0.1%) and nondiabetic subjects were studied during (0-120 min) and after (120-240 min) hypoglycemic (3.05 mmol/l) hyperinsulinemic (approximately 330 pmol/l) clamp tests. RESULTS: During hypoglycemia peak plasma concentrations of glucagon (199 +/- 16 vs. 155 +/- 11 ng/l, p < 0.05), epinephrine (4,514 +/- 644 vs. 1,676 +/- 513 pmol/l, p < 0.001), norepinephrine (2.21 +/- 0.14 vs. 1.35 +/- 0.19 nmol/l, p < 0.01) and cortisol (532 +/- 44 vs. 334 +/- 61 nmol/l) were reduced in the diabetic patients. Plasma lactate did not change from baseline values (0.51 +/- 0.06 mmol/l) in diabetic but doubled in healthy subjects (1.13 +/- 0.111 mmol/l, p < 0.001 vs. control). During the posthypoglycemic recovery period plasma concentrations of free fatty acids were higher in diabetic patients at 240 min (1.34 +/- 0.12 vs. 2.01 +/- 0.23 mmol/l, p < 0.05). CONCLUSION: Despite long-term near physiologic insulin substitution and the low incidence of hypoglycemia, hormonal hypoglycemia counterregulation was impaired in type-1 diabetic patients after a diabetes duration of more than 10 years.     

Dysregulation of muscle lipid metabolism in rats selectively bred for low aerobic running capacity

As substrate for evaluation of metabolic diseases, we developed novel rat models that contrast for endurance exercise capacity. Through two-way artificial selection, we created rodent phenotypes of intrinsically low-capacity runners (LCR) and high-capacity runners (HCR) that also differed markedly for cardiovascular and metabolic disease risk factors. Here, we determined skeletal muscle proteins with putative roles in lipid and carbohydrate metabolism to better understand the mechanisms underlying differences in whole body substrate handling between phenotypes. Animals (generation 16) differed for endurance running capacity by 295%. LCR animals had higher resting plasma glucose (6.58 +/- 0.45 vs. 6.09 +/- 0.45 mmol/l), insulin (0.48 +/- 0.03 vs. 0.32 +/- 0.02 ng/ml), nonesterified fatty acid (0.57 +/- 0.14 v 0.35 +/- 0.05 mM), and triglyceride (TG; 0.47 +/- 0.11 vs. 0.25 +/- 0.08 mmol/l) concentrations (all P < 0.05). Muscle TG (72.3 +/- 14.7 vs. 38.9 +/- 6.2 mmol/kg dry muscle wt; P < 0.05) and diacylglycerol (96 +/- 28 vs. 42 +/- 8 pmol/mg dry muscle wt; P < 0.05) contents were elevated in LCR vs. HCR rats. Accompanying the greater lipid accretion in LCR was increased fatty acid translocase/CD36 content (1,014 +/- 80 vs. 781 +/- 70 arbitrary units; P < 0.05) and reduced TG lipase activity (0.158 +/- 0.0125 vs. 0.274 +/- 0.018 mmol.min(-1).kg dry muscle wt(-1); P < 0.05). Muscle glycogen, GLUT4 protein, and basal phosphorylation states of AMP-activated protein kinase-alpha1, AMP-activated protein kinase-alpha2, and acetyl-CoA carboxylase were similar in LCR and HCR. In conclusion, rats with low intrinsic aerobic capacity demonstrate abnormalities in lipid-handling capacity. These disruptions may, in part, be responsible for the increased risk of metabolic disorders observed in this phenotype.     

Characterization of hepatic and brain metabolism in young adults with glycogen storage disease type 1: a magnetic resonance spectroscopy study

In glycogen storage disease type 1 (GSD1), children present with severe hypoglycemia, whereas the propensity for hypoglycemia may decrease with age in these patients. It was the aim of this study to elucidate the mechanisms for milder hypoglycemia symptoms in young adult GSD1 patients. Four patients with GSD1 [body mass index (BMI) 23.2 +/- 6.3 kg/m, age 21.3 +/- 2.9 yr] and four healthy controls matched for BMI (23.1 +/- 3.0 kg/m) and age (24.0 +/- 3.1 yr) were studied. Combined (1)H/(31)P nuclear magnetic resonance spectroscopy (NMRS) was used to assess brain metabolism. Before and after administration of 1 mg glucagon, endogenous glucose production (EGP) was measured with d-[6,6-(2)H(2)]glucose and hepatic glucose metabolism was examined by (1)H/(13)C/(31)P NMRS. At baseline, GSD1 patients exhibited significantly lower rates of EGP (0.53 +/- 0.04 vs. 1.74 +/- 0.03 mg.kg(-1).min(-1); P < 0.01) but an increased intrahepatic glycogen (502 +/- 89 vs. 236 +/- 11 mmol/l; P = 0.05) and lipid content (16.3 +/- 1.1 vs. 1.4 +/- 0.4%; P < 0.001). After glucagon challenge, EGP did not change in GSD1 patients (0.53 +/- 0.04 vs. 0.59 +/- 0.24 mg.kg(-1).min(-1); P = not significant) but increased in healthy controls (1.74 +/- 0.03 vs. 3.95 +/- 1.34; P < 0.0001). In GSD1 patients, we found an exaggerated increase of intrahepatic phosphomonoesters (0.23 +/- 0.08 vs. 0.86 +/- 0.19 arbitrary units; P < 0.001), whereas inorganic phosphate decreased (0.36 +/- 0.08 vs. -0.43 +/- 0.17 arbitrary units; P < 0.01). Intracerebral ratios of glucose and lactate to creatine were higher in GSD1 patients (P < 0.05 vs. control). Therefore, hepatic defects of glucose metabolism persist in young adult GSD1 patients. Upregulation of the glucose and lactate transport at the blood-brain barrier could be responsible for the amelioration of hypoglycemic symptoms.     

Urocortin 1 administration from onset of rapid left ventricular pacing represses progression to overt heart failure

Urocortin 1 (Ucn1) may be involved in the pathophysiology of heart failure (HF), but the impact of Ucn1 administration on progression of the disease is unknown. The aim of this study was to investigate the effects of Ucn1 in sheep from the onset of cardiac overload and during the subsequent development of HF. Eight sheep underwent two 4-day periods of HF induction by rapid left ventricular pacing (225 beats/min) in conjunction with continuous infusions of Ucn1 (0.1 microg.kg(-1).h(-1) iv) and a vehicle control (0.9% saline). Compared with control, Ucn1 attenuated the pacing-induced decline in cardiac output (2.43 +/- 0.46 vs. 3.70 +/- 0.89 l/min on day 4, P < 0.01) and increases in left atrial pressure (24.9 +/- 1.0 vs. 11.9 +/- 1.1 mmHg, P < 0.001) and peripheral resistance (38.7 +/- 9.4 vs. 25.2 +/- 6.1 mmHg.l(-1).min, P < 0.001). Ucn1 wholly prevented increases in plasma renin activity (4.02 +/- 1.17 vs. 0.87 +/- 0.1 nmol.l(-1).h(-1), P < 0.001), aldosterone (1,313 +/- 324 vs. 413 +/- 174 pmol/l, P < 0.001), endothelin-1 (3.8 +/- 0.5 vs. 2.0 +/- 0.1 pmol/l, P < 0.001), and vasopressin (10.8 +/- 4.1 vs. 1.8 +/- 0.2 pmol/l, P < 0.05) during pacing alone and blunted the progressive increases in plasma epinephrine (2,132 +/- 697 vs. 1,250 +/- 264 pmol/l, P < 0.05), norepinephrine (3.61 +/- 0.73 vs. 2.07 +/- 0.52 nmol/l, P < 0.05), and atrial (P < 0.05) and brain (P < 0.01) natriuretic peptide levels. Ucn1 administration also maintained urine sodium excretion (0.75 +/- 0.34 vs. 1.59 +/- 0.50 mmol/h on day 4, P < 0.05) and suppressed pacing-induced declines in creatinine clearance (P < 0.05). These findings indicate that Ucn1 treatment from the onset of cardiac overload has the ability to repress the ensuing hemodynamic and renal deterioration and concomitant adverse neurohumoral activation, thereby delaying the development of overt HF. These data strongly support a use for Ucn1 as a therapeutic option early in the course of the disease.     

Type 2 diabetic patients may have a mild form of an injury response: a clinical research center study

Patients with type 2 diabetes (DM) demonstrate inadequate insulin release, elevated gluconeogenesis, and diminished nonoxidative glucose disposal. Similar metabolic changes occur during systemic injury caused by infection, trauma, or cancer. Described here are metabolic changes occurring in 16 DM and 11 lung cancer patients (CA) and 13 normal volunteers (NV). After a 10-h overnight fast, all subjects had fasting hormone and substrate concentrations determined, along with rates of glucose production, leucine appearance (LA), and leucine oxidation (LO). Fasting insulin (data not shown) and C-peptide concentrations were elevated in DM and CA compared with weight-matched NV (0.72 +/- 0.09 and 0.64 +/- 0.08 vs. 0.51 +/- 0.03 mg/l, P < 0.05). C-reactive protein concentration was elevated in CA compared with DM and NV (23.3 +/- 6.0 vs. 4.2 +/- 1.4 and 2.1 +/- 0.5 mg/l, P < 0.01). All counterregulatory hormones were normal except for serum cortisol (11.4 +/- 1.0 and 12.1 +/- 1.0 vs. 8.9 +/- 0.7 microg/dl, DM and CA vs. NL, respectively, P < 0.05). Glucose production was increased in DM and CA compared with NV (4.22 +/- 0.6 and 3.53 +/- 0.3 vs. 2.76 +/- 0.2 mg x kg lean body wt(-1) x min(-1), P < 0.01). LO and LA were increased in DM and CA compared with NV (LO: 27.3 +/- 1.5 and 19.7 +/- 1.5 vs. 12.5 +/- 1.1 mmol x kg lean body wt(-1) x min(-1), P < 0.05; LA: 91.9 +/- 6.6 and 90.7 +/- 7.0 vs. 79.1 +/- 6.0 mmol. kg lean body wt(-1) x min(-1), P < 0.01). DM share similar metabolic derangements with CA. The increase in LA may be secondary to an increased glucose production where amino acids are mobilized to provide the liver with adequate substrate to make glucose. The increase in glucose production may also be part of the injury response, or it may represent a form of insulin resistance that exists in both the DM and (non-DM) CA patients.     

Suppressing lipolysis increases interleukin-6 at rest and during prolonged moderate-intensity exercise in humans.

IL-6 induces lipolysis when administered to humans. Consequently, it has been hypothesized that IL-6 is released from skeletal muscle during exercise to act in a "hormonelike" manner and increase lipolysis from adipose tissue to supply the muscle with substrate. In the present study, we hypothesized that suppressing lipolysis, and subsequent free fatty acid (FFA) availability, would result in a compensatory elevation in IL-6 at rest and during exercise. First, we had five healthy men ingest nicotinic acid (NA) at 30-min intervals for 120 min at rest [10 mg/kg body mass (initial dose), 5 mg/kg body mass (subsequent doses)]. Plasma was collected and analyzed for FFA and IL-6. After 120 min, plasma FFA concentration was attenuated (0 min: 0.26 +/- 0.05 mmol/l; 120 min: 0.09 +/- 0.02 mmol/l; P < 0.01), whereas plasma IL-6 was concomitantly increased approximately eightfold (0 min: 0.75 +/- 0.18 pg/ml; 120 min: 6.05 +/- 0.89 pg/ml; P < 0.001). To assess the effect of lipolytic suppression on the exercise-induced IL-6 response, seven active, but not specifically trained, men performed two experimental exercise trials with (NA) or without [control (Con)] NA ingestion 60 min before (10 mg/kg body mass) and throughout (5 mg/kg body mass every 30 min) exercise. Blood samples were obtained before ingestion, 60 min after ingestion, and throughout 180 min of cycling exercise at 62 +/- 5% of maximal oxygen consumption. IL-6 gene expression, in muscle and adipose tissue sampled at 0, 90, and 180 min, was determined by using semiquantitative real-time PCR. IL-6 mRNA increased in Con (rest vs. 180 min; P < 0.01) approximately 13-fold in muscle and approximately 42-fold in fat with exercise. NA increased (rest vs. 180 min; P < 0.01) IL-6 mRNA 34-fold in muscle, but the treatment effect was not statistically significant (Con vs. NA, P = 0.1), and 235-fold in fat (Con vs. NA, P < 0.01). Consistent with the study at rest, NA completely suppressed plasma FFA (180 min: Con, 1.42 +/- 0.07 mmol/l; NA, 0.10 +/- 0.01 mmol/l; P < 0.001) and increased plasma IL-6 (180 min: Con, 9.81 +/- 0.98 pg/ml; NA, 19.23 +/- 2.50 pg/ml; P < 0.05) during exercise. In conclusion, these data demonstrate that circulating IL-6 is markedly elevated at rest and during prolonged moderate-intensity exercise when lipolysis is suppressed.     

Glucose kinetics and substrate oxidation during exercise in the follicular and luteal phases.

The purpose of this investigation was to determine whether plasma glucose kinetics and substrate oxidation during exercise are dependent on the phase of the menstrual cycle. Once during the follicular (F) and luteal (L) phases, moderately trained subjects [peak O(2) uptake (V(O(2))) = 48.2 +/- 1.1 ml. min(-1). kg(-1); n = 6] cycled for 25 min at approximately 70% of the V(O(2)) at their respective lactate threshold (70%LT), followed immediately by 25 min at 90%LT. Rates of plasma glucose appearance (R(a)) and disappearance (R(d)) were determined with a primed constant infusion of [6,6-(2)H]glucose, and total carbohydrate (CHO) and fat oxidation were determined with indirect calorimetry. At rest and during exercise at 70%LT, there were no differences in glucose R(a) or R(d) between phases. CHO and fat oxidation were not different between phases at 70%LT. At 90%LT, glucose R(a) (28.8 +/- 4.8 vs. 33.7 +/- 4.5 micromol. min(-1). kg(-1); P < 0.05) and R(d) (28.4 +/- 4.8 vs. 34.0 +/- 4.1 micromol. min(-1). kg(-1); P < 0.05) were lower during the L phase. In addition, at 90%LT, CHO oxidation was lower during the L compared with the F phase (82.0 +/- 12.3 vs. 93.8 +/- 9.7 micromol. min(-1) .kg(-1); P < 0.05). Conversely, total fat oxidation was greater during the L phase at 90%LT (7.46 +/- 1.01 vs. 6.05 +/- 0.89 micromol. min(-1). kg(-1); P < 0.05). Plasma lactate concentration was also lower during the L phase at 90%LT concentrations (2.48 +/- 0.41 vs. 3.08 +/- 0.39 mmol/l; P < 0.05). The lower CHO utilization during the L phase was associated with an elevated resting estradiol (P < 0.05). These results indicate that plasma glucose kinetics and CHO oxidation during moderate-intensity exercise are lower during the L compared with the F phase in women. These differences may have been due to differences in circulating estradiol.     

Metabolic basis of HIV-lipodystrophy syndrome

Human immunodeficiency virus (HIV)-lipodystrophy syndrome (HLS) is characterized by hypertriglyceridemia, low high-density lipoprotein-cholesterol, lipoatrophy, and central adiposity. We investigated fasting lipid metabolism in six men with HLS and six non-HIV-infected controls. Compared with controls, HLS patients had lower fat mass (15.9 +/- 1.3 vs. 22.3 +/- 1.7 kg, P < 0.05) but higher plasma glycerol rate of appearance (R(a)), an index of total lipolysis (964.71 +/- 103.33 vs. 611.08 +/- 63.38 micromol x kg fat(-1) x h(-1), P < 0.05), R(a) palmitate, an index of net lipolysis (731.49 +/- 72.36 vs. 419.72 +/- 33.78 micromol x kg fat(-1) x h(-1), P < 0.01), R(a) free fatty acids (2,094.74 +/- 182.18 vs. 1,470.87 +/- 202.80 micromol x kg fat(-1) x h(-1), P < 0.05), and rates of intra-adipocyte (799.40 +/- 157.69 vs. 362.36 +/- 74.87 micromol x kg fat(-1) x h(-1), P < 0.01) and intrahepatic fatty acid reesterification (1,352.08 +/- 123.90 vs. 955.56 +/- 124.09 micromol x kg fat(-1) x h(-1), P < 0.05). Resting energy expenditure was increased in HLS patients (30.51 +/- 2.53 vs. 25.34 +/- 1.04 kcal x kg lean body mass(-1) x day(-1), P < 0.05), associated with increased non-plasma-derived fatty acid oxidation (139.04 +/- 24.17 vs. 47.87 +/- 18.81 micromol x kg lean body mass(-1) x min(-1), P < 0.02). The lipoatrophy observed in HIV lipodystrophy is associated with accelerated lipolysis. Increased hepatic reesterification promotes the hypertriglyceridemia observed in this syndrome.     

Nutrition level and season of birth do not modify puberty of Payoya goat kids

This study analysed the effect of level of nutrition and date of birth (age) on the onset of puberty in Payoya she-kids born in autumn (November) or in winter (February). Two experiments were conducted to examine pubertal events at the onset of puberty. For each date of birth (age), two experimental groups were used, differing on the level of nutrition. Groups were balanced for live weight (LW) and body condition score (BCS). For the first experiment (goat kids born in autumn), 27 Payoya she-kids were used: high-nutrition group (H1, n = 13) and control group (C1, n = 14). For the second experiment (goat kids born in winter), 25 Payoya she-kids were used: high-nutrition group (H2, n = 13) and control group (C2, n = 12). In both experiments, the level of feeding was adjusted weekly according to LW so that the animals would gain about 50 and 100 g per day for C and H groups, respectively. Oestrus was tested daily using young aproned bucks. Ovulation rate was assessed by laparoscopy 7 days after identification of oestrus. Plasma samples were obtained weekly for progesterone assay. LW and BCS were recorded weekly. No effect of nutrition level or birth date (Experiment 1 v. 2) on the date of the first ovarian activity or the first detected oestrus was observed. No effect of nutrition on LW or BCS at the first detected oestrus was observed. Birth date influenced significantly the LW of the animals at the onset of ovarian activity or first oestrus (P < 0.001). Irregular sexual activity was frequently observed before the first oestrus (74.7% and 48.0% of the first reproductive activity was irregular for Experiments 1 and 2, respectively). No effect of nutrition level or birth date on ovulation rate was observed. Ovulation rate at first oestrus was influenced by LW in November-born goat kids (1.06 ± 0.06 v. 1.67 ± 0.21 corpora lutea for LW < 30 and 30 kg, respectively, P < 0.01). These results demonstrate that the age at puberty was very dependent upon the season of birth in Payoya goat kids, and that there could be some benefit in breeding November-born goat kids at a higher LW to obtain a higher prolificacy at the first kidding as a consequence of a higher ovulation rate at puberty.     

Dietary protein reduction in sheep and goats: different effects on <Emphasis Type="SmallCaps">l</Emphasis>-alanine and <Emphasis Type="SmallCaps">l</Emphasis>-leucine transport across the brush-border membrane of jejunal enterocytes

It was the aim of this study to examine the potential regulatory effects of a long-term low dietary protein supply on the transport capacity of the jejunal brush-border membrane for amino acids. For this purpose, we used the neutral amino acids L-alanine (representative for nonessential amino acids) and L-leucine (representative for essential amino acids) as model substances. Ten sheep lambs, 8 weeks of age and 19-27 kg body weight, were allotted to two dietary regimes with either adequate or reduced protein supply which was achieved by 17.9% and 9.7% of crude protein in the concentrated feed, respectively. The feeding periods were 4-6 weeks in length. Similarly, eight goat kids of 5-7 weeks of age and 8-14 kg body weight were allotted to either adequate (crude protein 20.1%, feeding period 9-12 weeks) or reduced protein supply (10.1%, feeding period 17-18 weeks). Dietary protein reduction in lambs caused a significant body weight loss of 0.6 +/- 0.7 kg, whereas the body weight in control animals increased by 1.9 +/- 0.7 kg (P<0.05). Plasma urea concentrations decreased significantly by 60% (low protein 2.3 +/- 0.1 versus control 5.7 +/- 0.2 mmol l(-1), P<0.001). In kids, reduction of dietary protein intake led to significant decreases of the daily weight gain by 48% from 181 +/- 8 g to 94 +/- 3 g (P<0.001) and daily dry matter intake by 27% from 568 +/- 13 g to 417 +/- 6 g (P<0.01). Respective urea concentrations in plasma were reduced by 77% from 5.2 +/- 0.4 to 1.2 +/- 0.2 mmol l(-1) (P<0.01). Kinetic analyses of the initial rates of alanine uptake into isolated jejunal brush-border membrane vesicles from sheep and goats as affected by low dietary protein supply yielded that the apparent Km was neither significantly different between the species nor significantly affected by the feeding regime thus ranging between 0.12 and 0.16 mmol.l(-1). Reduction of dietary protein, however, resulted in significantly decreased Vmax values of the transport system by 25-30%, irrespective of the species. Kinetic analyses of the initial rates of leucine uptake into jejunal brush-border membrane vesicles from sheep and goats yielded that leucine uptake was mediated by Na+-dependent as well as Na+-independent processes. Similar to alanine, apparent Km values of leucine uptake were neither different between the species nor affected due to low dietary protein and ranged between 0.08 and 0.15 mmol l(-1). In contrast to the alanine transport mechanism, dietary protein reduction resulted in increased Vmax values of Na+-dependent leucine transport by 53% in sheep and 230% in goats. Similarly, Na+-independent leucine uptake was stimulated by 85% and 200% in sheep and in goats, respectively. This study shows adaptation of amino acid absorption at the brush-border membrane level of jejunal enterocytes of small ruminants due to dietary protein reduction. Whereas the transport capacity for the nonessential amino acid alanine was reduced due to low dietary protein, the transport capacity for the essential amino acid leucine was markedly stimulated. From this, the involvement of rather different feedback mechanisms in adaptation of intestinal amino acid transport mechanisms has to be discussed.     

Effects of tiadenol and clofibrate on plasma post heparin lipolytic hepatic, extrahepatic and monoglyceride hydrolase activities in rats with hypertriglyceridemia induced by a sucrose rich diet

Normal rats fed an isocaloric sucrose-rich diet (SRD) for 3 weeks developed high levels of triacylglycerol in plasma (P) (mmol triacylglycerol I-1) heart (H) and liver (L) tissues (mumol triacylglycerol mg DNA-1) as compared to control rats fed the standard chow (STD) (X +/- SEM; P: SRD 1.32 +/- 0.06 vs STD 0.49 +/- 0.05, P less than 0.001; H: SRD 2.1 +/- 0.17 vs STD 0.94 +/- 0.01, P less than 0.001; L: SRD 8.48 +/- 1.47 vs STD 1.71 +/- 0.12, P less than 0.001). A simultaneous drop in the activities (mumol glycerol ml-1 hr-1) of several plasma post heparin lipolytic enzymes was observed; total triglyceride lipase (T-TGL): SRD 5.32 +/- 0.34 vs STD 7.48 +/- 0.64, P less than 0.01; lipoprotein lipase (LPL): SRD 1.61 +/- 0.26 vs STD 2.42 +/- 0.41, P less than 0.05; hepatictriglyceride lipase (H-TGL): SRD 3.71 +/- 0.28 vs STD 5.05 +/- 0.69, P less than 0.05 and monoglyceride hydrolase (MGH) (mumol glycerol I-1 min-1): SRD 558 +/- 108 vs STD 1165 +/- 45, P less than 0.001. Rats fed the SRD presented glucose intolerance after i.v. glucose (Kg X 10(-2); 1.06 +/- 0.09 vs 2.61 +/- 0.14 of STD, P less than 0.001) in spite of the presence of hyperinsulinism (sigma plasma IRI microU/ml from 0 to 30 min: 184.6 +/- 23.6 vs 100.5 +/- 9.7 of STD, P less than 0.01) suggesting that a state of insulin resistance had developed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diversity in levels of intracellular total creatine and triglycerides in human skeletal muscles observed by (1)H-MRS.

We used (1)H-magnetic resonance spectroscopy to noninvasively determine total creatine (TCr), choline-containing compounds (Cho), and intracellular (IT) and extracellular (between-muscle fibers) triglycerides (ET) in three human skeletal muscles. Subjects' (n = 15 men) TCr concentrations in soleus [Sol; 100.2 +/- 8.3 (SE) mmol/kg dry wt] were lower (P < 0.05) than those in gastrocnemius (Gast; 125.3 +/- 9.2 mmol/kg dry wt) and tibialis anterior (TA; 123. 7 +/- 8.8 mmol/kg dry wt). The Cho levels in Sol (35.8 +/- 3.6 mmol/kg dry wt) and Gast (28.5 +/- 3.5 mmol/kg dry wt) were higher (P < 0.001 and P < 0.01, respectively) compared with TA (13.6 +/- 2. 4 mmol/kg dry wt). The IT values were found to be 44.8 +/- 4.6 and 36.5 +/- 4.2 mmol/kg dry wt in Sol and Gast, respectively. The IT values of TA (24.5 +/- 4.5 mmol/kg dry wt) were lower than those of Sol (P < 0.01) and Gast (P < 0.05). There were no differences in ET [116.0 +/- 11.2 (Sol), 119.1 +/- 18.5 (Gast), and 91.4 +/- 19.2 mmol/kg dry wt (TA)]. It is proposed that the differences in metabolite levels may be due to the differences in fiber-type composition and deposition of metabolites due to the adaptation of different muscles during locomotion.     

Increased body fat in streptozotocin diabetic rats treated with intensive subcutaneous insulin therapy vs. islet transplantation

The continued development of novel insulin treatment is predicated on the hypothesis that strict glycemic control is necessary to prevent the secondary complications of diabetes. Although dramatically successful in reducing selected secondary complications, intensive insulin therapy has consequences. These include hypoglycemia, weight gain, and body fat accumulation. In the present studies we compared a model of intensive insulin therapy in diabetic rats and contrasted weight gain and body fat accumulation with pancreatic islet transplantation. Female Wistar Furth rats (173 g) administered streptozotocin (55 mg x kg(-1), iv) remained diabetic (DB) for four or nine weeks. At week three, a third group was transplanted (TRAN) with islets of Langerhans (3519 +/- 838 150 microm islets); one week later group four began intensive subcutaneous insulin therapy (ISIT; 4 x 0.5-1.0 U regular insulin x day(-1)). Within one week ISIT rats had normalized plasma glucose; levels were not different from age matched controls (CN) or TRAN animals (ISIT 10.6 +/- 1.7, CN 7.2 +/- 0.4, TRAN 7.7 +/- 0.8 mmol x L(-1), P > 0.05). The cumulative occurrence of one episode of hypoglycemia (< 2.8 mmol x L(-1)) occurred in 50% of ISIT rats. At study termination, body weight of ISIT and CN rats did not differ (199 +/- 4 vs. 207 +/- 3, P > 0.05). While carcass protein content was similar for TRAN, ISIT, and CN animals, the body fat of ISIT animals was 24% greater than in CN rats and 21% greater than in TRAN rats (P < 0.05). Correlation of body fat vs. plasma glucose illustrated hypoglycemia contributed to the body fat gain of ISIT rats (n = 8, r = -0.70, P = 0.0535). These studies illustrate a disproportionate gain of body fat from ISIT, an effect not observed with islet transplantation. Thus, the metabolic benefit ascribed to islet transplantation appears related to the absence of hypoglycemia.     

Selected contribution: skeletal muscle capillarity and enzyme activity in rats selectively bred for running endurance.

To attempt to explain the difference in intrinsic (untrained) endurance running capacity in rats selectively bred over seven generations for either low (LCR) or high running capacity (HCR), the relationship among skeletal muscle capillarity, fiber composition, enzyme activity, and O(2) transport was studied. Ten females from each group [body wt: 228 g (HCR), 247 g (LCR); P = 0.03] were studied at 25 wk of age. Peak normoxic maximum O(2) consumption and muscle O(2) conductance were previously reported to be 12 and 33% higher, respectively, in HCR, despite similar ventilation, arterial O(2) saturation, and a cardiac output that was <10% greater in HCR compared with LCR. Total capillary and fiber number in the medial gastrocnemius were similar in HCR and LCR, but, because fiber area was 37% lower in HCR, the number of capillaries per unit area (or mass) of muscle was higher in HCR by 32% (P < 0.001). A positive correlation (r = 0.92) was seen between capillary density and muscle O(2) conductance. Skeletal muscle enzymes citrate synthase and beta-hydroxyacyl-CoA dehydrogenase were both approximately 40% higher (P < 0.001) in HCR (12.4 +/- 0.7 vs. 8.7 +/- 0.4 and 3.4 +/- 0.2 vs. 2.4 +/- 0.2 mmol. kg(-1). min(-1), respectively), whereas phosphofructokinase was significantly (P = 0.02) lower in HCR (27.8 +/- 1.2 vs. 35.2 +/- 2.5 mmol. kg(-1). min(-1)) and hexokinase was the same (0.65 +/- 0.04 vs. 0.65 +/- 0.03 mmol. kg(-1). min(-1)). Resting muscle ATP, phosphocreatine, and glycogen contents were not different between groups. Taken together, these data suggest that, in rats selectively bred for high-endurance exercise capacity, most of the adaptations for improved O(2) utilization occur peripherally in the skeletal muscles and not in differences at the level of the heart or lung.     

Carcass composition and meat quality of indigenous Yanan pigs of China

The Yanan (YN) pig is a traditional Chinese indigenous breed that is raised in southwest China in the Sichuan Province, but there is little data on the germplasm characteristics of this breed. To evaluate carcass characteristics and meat quality of the YN pig, we compared carcass and meat quality of YN pigs and Landrace × Yanan (CY) hybrid pigs; 30 YN pigs and 30 CY pigs weighing 20 ± 2 kg were reared and slaughtered at the normal slaughter weight (100-120 kg). The carcasses were chilled and the left carcass side was dissected into bone, lean meat, fat, and skin; meat quality parameters were measured. Carcasses of YN pigs were lighter (88.85 vs 90.05 kg, P < 0.05) and shorter (71.88 vs 77.61 cm, P < 0.001); they contained less lean meat (41.60 vs 49.25%, P < 0.001), less ham and breech (25.93 vs 27.53%, P < 0.001) and less carcass bone (9.83 vs 10.53%, P < 0.01) than did carcasses of CY pigs. On the other hand, YN pigs had more carcass subcutaneous fat and skin (48.58 vs 40.23%, P < 0.001), thicker backfat (3.67 vs 3.43 cm, P < 0.001) and smaller loin muscle area (9.83 vs 26.91 cm(2), P < 0.001) compared with CY pigs. Among meat quality parameters, YN pigs had higher pH(1) (6.41 vs 6.17, P < 0.001), higher color score(u) (3.86 vs 3.36, P < 0.001) and lower Minolta L(u) values (40.89 vs 45.32, P < 0.01) than CY pigs. On the other hand, YN pigs had lower drip loss (1.31 vs 2.26%, P < 0.05) and lesser fiber area (2351.34 vs 3025.43 μm(2), P < 0.01) than CY pigs. Both breeds had high intramuscular fat (4.46% in YN and 4.45% in CY). No significant differences in other carcass traits and meat quality were found in the two populations. We conclude that YN pigs could be used in commercial pig production to provide good tasting and high-quality niche products.     

利拉鲁肽联合二甲双胍对肥胖合并2型糖尿病患者糖脂代谢、胰岛β细胞功能及体脂的影响探究

目的探讨利拉鲁肽联合二甲双胍对肥胖合并2型糖尿病患者糖脂代谢、胰岛β细胞功能及体脂的影响。 方法选择成都市郫都区第二人民医院2017年1月至2018年12月收治的肥胖合并2型糖尿病患者141例作为研究对象,按照随机数字表法分为利拉鲁肽组47例、二甲双胍组47例与联合组47例。利拉鲁肽组采用利拉鲁肽治疗,二甲双胍组采用二甲双胍治疗,联合组采用利拉鲁肽联合二甲双胍治疗。三组疗程均为3个月。比较三组治疗前后糖代谢、脂代谢、胰岛β细胞功能和体重指数（BMI）变化,及不良反应,治疗前后比较采用配对t检验,三组间比较采用F检验,两组间比较采用LSD-t检验。 结果三组治疗后FPG、HbA1c和2hPG水平较治疗前降低,差异具有统计学意义（P均< 0.05）;联合组治疗后FPG（6.57±0.39）?mmol/L、HbA1c（7.03±0.42）%和2hPG（8.78±0.45）mmol/L低于利拉鲁肽组（7.03±0.32）mmol/ L、（7.68±0.35）%、（9.56±0.65）mmol/L（t = 6.251、8.151、6.764,P均?< 0.05）和二甲双胍组（7.06±0.39）mmol/L、（7.76±0.46）%、（9.70±0.81）?mmol/L,差异具有统计学意义（t = 6.091、8.034、6.807,P均< 0.05）。三组治疗后HDL-C水平较治疗前升高,而TC、LDL-C和TG水平较治疗前降低,差异具有统计学意义（P均< 0.05）;联合组治疗后HDL-C （1.56±0.13） mmol/ L高于利拉鲁肽组（1.29±0.14） mmol/ L（t = 9.689,P < 0.05）和二甲双胍组（1.32±0.15） mmol/ L,差异具有统计学意义（t = 8.289,P < 0.05）;而联合组TC（4.35±0.38） mmol/L、LDL-C（2.79±0.21）mmol/L和TG（2.15±0.26） mmol/ L低于利拉鲁肽组（5.18±0.43）mmol/L、（3.19±0.15）mmol/L、（2.65±0.17） mmol/L（t = 9.916、10.626、11.035,P < 0.05）和二甲双胍组（5.15±0.34）mmol/L、（3.23±0.25）mmol/ L、（2.68±0.23） mmol/ L,差异具有统计学意义（t = 10.756、9.239、10.467,P均< 0.05）。三组治疗后HOMA-β较治疗前升高,差异具有统计学意义（P < 0.05）;联合组治疗后HOMA-β（4.87±0.28）高于利拉鲁肽组（4.15±0.36）和二甲双胍组（4.08±0.41）,差异具有统计学意义（t = 10.823,10.909,P均< 0.05）。三组治疗后BMI较治疗前降低,差异具有统计学意义（P < 0.05）;联合组治疗后BMI （28.08±0.37）kg/m²低于利拉鲁肽组（29.73±0.49）kg/m²和二甲双胍组（29.61±0.43）kg/m²,差异具有统计学意义（t = 18.423,18.490,P均< 0.05）。 结论利拉鲁肽联合二甲双胍对肥胖合并2型糖尿病患者效果良好,可改善患者糖脂代谢和胰岛β细胞功能,降低体质指数,值得临床借鉴。     

Insulin action on protein metabolism in acromegalic patients

Insulin resistance in acromegaly causes glucose intolerance and diabetes, but it is unknown whether it involves protein metabolism, since both insulin and growth hormone promote protein accretion. The effects of acromegaly and of its surgical cure on the insulin sensitivity of glucose and amino acid/protein metabolism were evaluated by infusing [6,6-(2)H(2)]glucose, [1-(13)C]leucine, and [2-(15)N]glutamine during a euglycemic insulin (1 mU x kg(-1) x min(-1)) clamp in 12 acromegalic patients, six studied again 6 mo after successful adenomectomy, and eight healthy controls. Acromegalic patients, compared with postsurgical and control subjects, had higher postabsorptive glucose concentration (5.5 +/- 0.3 vs. 4.9 +/- 0.2 micromol/l, P < 0.05, and 5.1 +/- 0.1 micromol/l) and flux (2.7 +/- 0.1 vs. 2.0 +/- 0.2 micromol x kg(-1) x min(-1), P < 0.01, and 2.2 +/- 0.1 micromol x kg(-1) x min(-1), P < 0.05) and reduced insulin-stimulated glucose disposal (+15 +/- 9 vs. +151 +/- 18%, P < 0.01, and 219 +/- 58%, P < 0.001 from basal). Postabsorptive leucine metabolism was similar among groups. In acromegalic and postsurgical subjects, insulin suppressed less than in controls the endogenous leucine flux (-9 +/- 1 and -12 +/- 2 vs. -18 +/- 2%, P < 0.001 and P < 0.05), the nonoxidative leucine disposal (-4 +/- 3 and -1 +/- 3 vs. -18 +/- 2%, P < 0.01 and P < 0.05), respectively, indexes of proteolysis and protein synthesis, and leucine oxidation (-17 +/- 6% in postsurgical patients vs. -26 +/- 6% in controls, P < 0.05). Within 6 mo, surgery reverses insulin resistance for glucose but not for protein metabolism. After adenomectomy, more leucine is oxidized during hyperinsulinemia.     

Gender-specific effects of prenatal stress on emotional reactivity and stress physiology of goat kids

The aims of this study were to investigate the effects of maternal stress during pregnancy on the emotional reactivity, the hypothalamo-pituitary-adrenocortical (HPA) axis, and the sympatho-adrenomedullary (SAM) system of goat offspring according to their gender, and to investigate the role of maternal cortisol in prenatal stress effects. Goats were exposed to ten transports in isolation or ten ACTH injections (0.125 IU/kg body weight) during the last third of pregnancy. Control goats remained undisturbed. No effect of repeated transport during the last third of pregnancy was found on basal cortisol concentrations of the offspring. However, an increase in phenylethanolamine N-methyl transferase activity in the adrenals was observed in prenatally stressed kids compared to control kids (P = 0.031). In the presence of novelty, prenatally stressed female kids were more active (P = 0.049) than control females; they also showed more signs of arousal (P = 0.039) and tended to explore more of their environment (P = 0.053) in reaction to a startling stimulus. On the contrary, prenatally stressed male kids tended to be less active (P = 0.051) than control male kids but showed more signs of distress (P = 0.047) in the presence of novelty. Intermediate effects were found on the emotional reactivity to novelty of kids born from dams given injections of ACTH. In conclusion, transport stress in pregnant goats affects the sympatho-adrenomedullary system and the emotional reactivity of their offspring in a gender-specific manner. Moreover, the effects of prenatal transport and ACTH injections showed some similarities but differed in some critical details.     

Effect of fat adaptation and carbohydrate restoration on metabolism and performance during prolonged cycling.

For 5 days, eight well-trained cyclists consumed a random order of a high-carbohydrate (CHO) diet (9.6 g. kg(-1). day(-1) CHO, 0.7 g. kg(-1). day(-1) fat; HCHO) or an isoenergetic high-fat diet (2.4 g. kg(-1). day(-1) CHO, 4 g. kg(-1). day(-1) fat; Fat-adapt) while undertaking supervised training. On day 6, subjects ingested high CHO and rested before performance testing on day 7 [2 h cycling at 70% maximal O(2) consumption (SS) + 7 kJ/kg time trial (TT)]. With Fat-adapt, 5 days of high-fat diet reduced respiratory exchange ratio (RER) during cycling at 70% maximal O(2) consumption; this was partially restored by 1 day of high CHO [0.90 +/- 0.01 vs. 0.82 +/- 0.01 (P < 0.05) vs. 0.87 +/- 0.01 (P < 0.05), for day 1, day 6, and day 7, respectively]. Corresponding RER values on HCHO trial were [0. 91 +/- 0.01 vs. 0.88 +/- 0.01 (P < 0.05) vs. 0.93 +/- 0.01 (P < 0.05)]. During SS, estimated fat oxidation increased [94 +/- 6 vs. 61 +/- 5 g (P < 0.05)], whereas CHO oxidation decreased [271 +/- 16 vs. 342 +/- 14 g (P < 0.05)] for Fat-adapt compared with HCHO. Tracer-derived estimates of plasma glucose uptake revealed no differences between treatments, suggesting muscle glycogen sparing accounted for reduced CHO oxidation. Direct assessment of muscle glycogen utilization showed a similar order of sparing (260 +/- 26 vs. 360 +/- 43 mmol/kg dry wt; P = 0.06). TT performance was 30.73 +/- 1.12 vs. 34.17 +/- 2.48 min for Fat-adapt and HCHO (P = 0.21). These data show significant metabolic adaptations with a brief period of high-fat intake, which persist even after restoration of CHO availability. However, there was no evidence of a clear benefit of fat adaptation to cycling performance.