Effects of insulin on hepatic lipid synthesis in alloxan diabetic rats.

In vitro hepatic synthesis of lipids starting from 1-(14)C-acetate was studied in rats made diabetic by subcutaneous alloxan administration (175 mg/kg b.w.). A second group of diabetic rats was treated with lente insulin. In the alloxan-treated rats, a decrese was observed in hepatic incorporation of 1-(14)C-acetate into phospholipids, triglycerides and esterified cholesterol; there was an increased incorporation into nonesterified fatty acids (NEFA) and free cholesterol. Insulin administration restored lipid synthesis values to normal. On histologic examination, an intranuclear glycogenesis was observed in the hepatocytes of the alloxan-treated rats, along with severe hepatic necrosis; the latter however, only in rats sacrified on the 3rd day. Hepatic steatosis with small, medium and large droplets was present in the insulin-treated rats; signs of cellular degeneration were less evident.     

Increased resting lipid oxidation in Crohn's disease

Resting energy expenditure (REE) was measured by indirect calorimetry and body composition was assessed by both direct (bioimpedance) and indirect (anthropometry) methods in 20 hospitalized patients with biopsy-proven ileal Crohn's disease and in a group of 16 healthy volunteers matched for sex, age, and height with the patient group. The Crohn's disease activity index was below 120 in all patients studied. who were treated with a low dose of corticosteroids (0.2–0.3 mg/kg body wt of prednisone). The average weight of Crohn's patients was signficantly lower than that of controls (55.70 vs 70.50 kg,P<0.001) due to both lower fat mass (9.97 vs 18.30 kg,P<0.001) and lower lean body mass (45.72 vs 52.20 kg,P<0.02). The average REE was significantly higher in the control group (1785.42±7.503 vs 1559.1±48.39 kcal/day,P<0.001). However, these differences disappeared when REE was normalized by lean body mass (LBM) (34.49±2.56 vs 34.704±3.75 kcal/kg LBMP=NS). The nonprotein respiratory quotient was significantly lower in the patient group (0.823±0.031 vs 0.882±0.012.P<0.025), indicating an increased lipid oxidation. This increased lipid oxidation might explain the reduced fat stores found in the group of Crohn's patients, suggesting also that a sufficiently lipid-rich diet could be useful in their nutritional management.     

Use of dicarboxylic acids in type 2 diabetes

Even‐number, medium‐chain dicarboxylic acids (DAs), naturally occurring in higher plants, are a promising alternative energy substrate. Unlike the homologous fatty acids, DAs are soluble in water as salts. They are β‐oxidized, providing acetyl‐CoA and succinyl‐CoA, the latter being an intermediate of the tricarboxylic acid cycle. Sebacic acid and dodecanedioic acid, DAs with 10 and 12 carbon atoms respectively, provide 6.6 and 7.2 kcal g⁻¹ each; therefore, their energy density is intermediate between glucose and fatty acids. Dicarboxylic acids have been proved to be safe in both experimental animals and humans, and their use has recently been proposed in diabetes. Studies in animals and humans with type 2 diabetes showed that oral administration of sebacic acid improved glycaemic control, probably by enhancing insulin sensitivity, and reduced hepatic gluconeogenesis and glucose output. Moreover, dodecanedioic acid intake reduced muscle fatigue during exercise in subjects with type 2 diabetes, suggesting an improvement of energy utilization and ‘metabolic flexibility’. In this article, we review the natural sources of DAs, their fate in animals and humans and their effect in improving glucose metabolism in type 2 diabetes.     

Metabolic effects and disposition of sebacate, an alternate dicarboxylic fuel substrate.

Disodium sebacate is a 10-carbon-atom dicarboxylic acid, proposed as substrate for parenteral nutrition. We investigated its pharmacokinetic profile and thermogenic effect during a short-time infusion (5 h at 10 g/h) in 7 male volunteers. Sebacate in serum and urine was measured by high-performance liquid chromatography. A single-compartment model with two linear elimination routes was fitted. Metabolic measurements (VO2, VCO2, respiratory quotient, metabolic rate) were continuously performed for 8 h (5 h during and 3 h after the infusion) by a canopy indirect calorimeter. The apparent volume of distribution of sebacate was 8.39 +/- 0.69 liters, and the plasma fractional removal rate constant was 0.0086 +/- 0.00077 min-1. The average half-life and plasma clearance were 80.6 min and 72 ml/min, respectively. The increase in metabolic rate, the decrease in respiratory quotient and the changes in ketone body, glucagon and insulin levels during the infusion were not significant. 24-hour catecholamine excretion was within normal limits. Calories administered by sebacate seem to be available for utilization without relevant metabolic side effects.     

Differential effect of weight loss on insulin resistance in surgically treated obese patients

PURPOSE: To compare the effects of equivalent weight loss induced by two bariatric surgical techniques on insulin action in severely obese patients. METHODS: Eighteen nondiabetic patients with severe obesity (mean [+/- SD] body mass index: 53.5 +/- 9.0 kg/m(2)) and 20 sex- and age-matched lean subjects (body mass index: 23.8 +/- 3.0 kg/m(2)) underwent metabolic studies, including measurement of insulin sensitivity by the insulin clamp technique. Patients then underwent either vertical banded gastroplasty with Roux-en-Y gastric bypass, or biliopancreatic diversion, and were restudied at 5 to 6 months and again at 16 to 24 months postsurgery. RESULTS: At baseline, patients were hyperinsulinemic (194 +/- 47 pmol/L vs. 55 +/- 25 pmol/L, P < 0.0001), hypertriglyceridemic (1.56 +/- 0.30 mmol/L vs. 0.78 +/- 0.32 mmol/L, P < 0.0001), and profoundly insulin resistant (insulin-mediated glucose disposal: 20.8 +/- 4.4 micromol/min/kg fat-free mass vs. 52.0 +/- 10.1 micromol/min/kg, P < 0.0001) as compared with controls. Weight loss by the two procedures was equivalent in both amount (averaging -53 kg) and time course. In the gastric bypass group, insulin sensitivity improved (23.8 +/- 6.0 micromol/min/kg at 5 months and 33.7 +/- 11.3 micromol/min/kg at 16 months, P < 0.01 vs. baseline and controls). In contrast, in the biliopancreatic diversion group, insulin sensitivity was normalized already at 6 months (52.5 +/- 12.4 micromol/min/kg, P = 0.72 vs. controls) and increased further at 24 months (68.7 +/- 9.5 micromol/min/kg, P < 0.01 vs. controls) despite a persistent obese phenotype (body mass index: 33.2 +/- 8.0 kg/m(2)). CONCLUSION: In surgically treated obese patients, insulin sensitivity improves in proportion to weight loss with use of predominantly restrictive procedures (gastric bypass), but is reversed completely by predominantly malabsorptive approaches (biliopancreatic diversion) long before normalization of body weight. Selective nutrient absorption and gut hormones may interact with one another in the genesis of the metabolic abnormalities of obesity.     

Characterization of bacteriophages infecting clinical isolates of Pseudomonas aeruginosa stored in a culture collection

Some clinical isolates of Pseudomonas aeruginosa stored in our culture collection did not grow or grew poorly and showed lysis on the culture plates when removed from the collection and inoculated on MacConkey agar. One hypothesis was that bacteriophages had infected and killed those clinical isolates. To check the best storage conditions to maintain viable P. aeruginosa for a longer time, clinical isolates were stored at various temperatures and were grown monthly. We investigated the presence of phage in 10 clinical isolates of P. aeruginosa stored in our culture collection. Four strains of P. aeruginosa were infected by phages that were characterized by electron microscopy and isolated to assess their ability to infect. The best condition to maintain the viability of the strains during storage was in water at room temperature. Three Siphoviridae and two Myoviridae phages were visualized and characterized by morphology. We confirmed the presence of bacteriophages infecting clinical isolates, and their ability to infect and lyse alternative hosts. Strain PAO1, however, did not show lysis to any phage. Mucoid and multidrug resistant strains of P. aeruginosa showed lysis to 50% of the phages tested.     

Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism: Multicentre prospective study by the ‘Nutritional Problems in Gastroenterology’ Section of the Italian Society of Gastroenterology (SIGE)

BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.