Glucose tolerance deteriorates with aging. To test whether age per se impairs basal beta-cell function, we analyzed retrospective clamp data from a large group (n = 957) of nondiabetic Europeans over the 18-85 yr age range (the European Group for the Study of Insulin Resistance database). In this cohort, the fasting posthepatic insulin delivery rate [IDR, obtained as the product of clamp-derived posthepatic insulin MCR and fasting plasma insulin concentration] was 8.9 (6.6) mU/min (median and interquartile range), and it gradually increased with age. In univariate association, IDR was positively related to body mass index (P < 0.0001), fasting plasma glucose (P < 0.01), and waist-to-hip ratio (P < 0.001), and negatively related to insulin sensitivity (P < 0.0001). After controlling for these factors in a multivariate model, IDR declined significantly with age (P < 0.0001). This intrinsic effect of age on IDR was similar in men and women, and it averaged 25% between 18-85 yr. In the same statistical model, insulin MCR (but not fasting plasma insulin concentration) showed a significant (P < 0.0001) inverse relation to age. We conclude that, in nondiabetic Caucasian subjects of either sex, senescence per se is associated with a progressive decline in both insulin clearance and basal insulin release.

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Independent Influence of Age on Basal Insulin Secretion in Nondiabetic Humans

1. Measurements were made of the nitrogen and energy balances of pigs of 30, 60 and 90 kg given a conventional diet at various daily rates. 2. Body protein synthesis was estimated from the irreversible loss of leucine from the blood following the infusion of [1-14C]leucine, and from the oxidation of the labelled amino acid. 3. Protein synthesis (g/d) increased by 2.17 for each 1 g increase in daily protein accretion and by 1.55 for each 1 g increase in daily protein intake. 4. At 30 kg, pigs close to energy equilibrium synthesized 270 g protein daily compared with 406 g and 512 g when their ration supplied twice and three times their maintenance requirement. 5. There was a close correlation between the daily urinary excretion of urea + ammonia and total amino acid catabolism estimated from the catabolism of leucine, but the latter underestimated the observed excretion by 2.5 g N/d. 6. The results imply that protein turnover accounts for only a proportion of the heat production associated with protein deposition.

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Protein turnover in growing pigs. Effects of age and food intake

The present experiment was designed to elucidate the mechanism of the methionine-sparing effect of excess branched-chain amino acids (BCAA) reported in the previous paper (Langer & Fuller, 2000). Twelve growing gilts (30-35 kg) were prepared with arterial catheters. After recovery, they received for 7 d a semipurified diet with a balanced amino acid pattern. On the 7th day blood samples were taken before (16 h postabsorptive) and after the morning meal (4 h postprandial). The animals were then divided into three groups and received for a further 7 d a methionine-limiting diet (80% of requirement) (1) without any amino acid excess; (2) with excess leucine (50% over requirement); or (3) with excesses of all three BCAA (leucine, isoleucine, valine, each 50% over the requirement). On the 7th day blood samples were taken as in the first period, after which the animals were killed and liver and muscle samples taken. Plasma amino acid and branched-chain keto acid (BCKA) concentrations in the blood and branched-chain keto-acid dehydrogenase (BCKDH; EC 1.2.4.4) activity in liver and muscle homogenates were determined. Compared with those on the balanced diet, pigs fed on methionine-limiting diets had significantly lower (P < 0.05) plasma methionine concentrations in the postprandial but not in the postabsorptive state. There was no effect of either leucine or a mixture of all three BCAA fed in excess on plasma methionine concentrations. Excess dietary leucine reduced (P < 0.05) the plasma concentrations of isoleucine and valine in both the postprandial and postabsorptive states. Plasma concentrations of the BCKA reflected the changes in the corresponding amino acids. Basal BCKDH activity in the liver and total BCKDH activity in the biceps femoris muscle were significantly (P < 0.05) increased by excesses of leucine or all BCAA.

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Interactions among the branched-chain amino acids and their effects on methionine utilization in growing pigs: effects on plasma amino- and keto-acid concentrations and branched-chain keto-acid dehydrogenase activity.

The objective of the experiment was to define the form of the relationship between varying levels of protein and energy intake and the performance of young pigs. Forty-four young pigs were assigned at 12 kg live weight for 6 weeks either to an initial slaughter group (n 8) or to one of the nine feeding treatments (n 4); three allowances of a high-protein food with 355 g crude protein (nitrogen × 6.25; CP)/kg (P1, P2, P3) at three levels of feeding (L, M and H). Each feeding level was met by supplementing the allowance of feed P with the appropriate amount of starch and each treatment had two males and two females. The rate of protein deposition was not affected by feeding level at the two lowest allowances of basal feed P (P1 and P2), but it increased with increasing the feeding level for the pigs on treatment P3. Males deposited more protein than females, but this effect was more pronounced with treatment P3. The rate of lipid deposition increased with each increase in the level of feeding and decreased with increasing the allowance of feed P. The calculated efficiency of protein utilization (ep) was expressed as a function of the energy: protein ratio in the feed (MJ metabolizable energy/kg digestible CP). The best model to describe the relationship was a linear-plateau model, with the maximum value for ep of 0.814 at 73 MJ/kg. This relationship provided the basis of a model that could predict the response of a growing pig to its diet as rates of protein and lipid retention

The effects of varying protein and energy intakes on the growth and body composition of pigs. 2. The effects of varying both energy and protein intake.

1. The relationships between the intakes of protein and of non-protein energy (NPE), nitrogcn retention and body protein synthesis have been studied in female pigs weighing 30 and 35 kg.2. Four animals were assigned to three regimens and given a conventional (basal) diet supplemented with fat, carbohydrate or protein. After 1 week, measurements of N excretion in urine and faeces (7 d collection) and gaseous exchange (3–4 d) were made. At the end of the balance period a solution of [l-14C]leucine was infused at a constant rate. Body protein synthesis was then calculated as the difference between the apparent irreversible loss of blood leucine and the loss of 14C in expired air.The animals were then offered the basal diet without supplement for 10 d and the measurements of N retention, energy retention and protein synthesis were repeated.3. The intakes of metabolizable energy (ME; MJ/kg body-weight (W)0.75per d) were 1.75 for fat, 1.58 for carbohydrate, 1–25for protein and 1.18 for the basal diet; corresponding intakes of apparently digestible N (ADN; g N/kgW0.75 per d) were 2.30,2.31,4.35 and 2–17. Daily N retention, which during the period of basal feeding was 13.6 g was increased by between 3.4 and 7.2 g by the supplements. Daily fat deposition was also increased in the animals that received the diets supplemented with carbohydrate and fat.4. The rate of leucine catabolism was significantly reduced in the animals receiving the diets that were supplemented with W Eand increased by the addition of protein to the diet.5. When based on the specfic radioactivity of blood leucine both the synthesis and breakdown of body protein (per unit metabolic body-weight) were increased by 30% in the animals receiving the high-protein diet but the increases in protein synthesis associated with the addition of carbohydrate (+14%) and fat (+12%) were much less marked. Consideration of these results together with previous observations (Reeds et al. 1980) suggested that body protein synthesis(g N/d) increased by 0.88 for each g increase in daily ADN and by 0.93 for each MJ increase in daily ME intake.6. Comparison of the results obtained with the animals given high-carbohydrate diets and those given high-protein diets suggested an increase in heat production of 14 KJ/g of additional fat deposition. A similar comparison of animals receiving the high-protein and basal diets suggested a heat increment of 23.5KJ/g additional protein deposition. The changes in heat production and protein synthesis in the animals given the protein supplement were compatible with a heat increment of 5.3 KJ/g additional protein synthesized. Because of the large proportion of heat production associated with the deposition of fat this could not be confirmed with either of the other supplements, but it is possible that the energy cost of protein accretion varies with the relative proportions of protein and NPE in the diet.

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Effects of changes in the intakes of protein and non-protein energy on whole-body protein turnover in growing pigs.

1. In five experiments with growing female pigs of 38-63 kg, insulin (2 mU/kg) per min) and glucose (9-17 mg/kg per min) were infused continuously for 3-7 d. In three further experiments, glucose (9 mg/kg per min) was infused alone for 5 d. 2. In response to the combined infusion, plasma insulin increased 2-7-fold, plasma glucose decreased, on average, by 50% and plasma urea concentration was reduced by 40%. Urinary excretion of urea and nitrogen decreased after the first day of infusion to values averaging 70% of control levels. 3. The infusion of glucose alone provoked only a small increase in plasma insulin. The reduction of urinary urea and of N excretion were approximately 25% of those observed with the combined infusions.

A. Cadenhead

Papers

The protein-sparing effect of carbohydrate: 2.* The role of insulin