The Trp64 A rg mutation of the B3- Adrenergic Receptor Is associated with hyperglycemia and current body mass index in Jamaican women

The Trp64Arg mutation the the beta3-adrenergic receptor (beta3-AR) has been linked to earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), insulin resistance, abdominal obesity, and an increase capacity to gain weight in some European and Japanese populations. We studied the prevalence of the mutation and its association with NIDDM and obesity in our population, in which both rates are high, especially in women. The frequency of the homozygous mutation was 1.53 percent, and of the Arg allele, 10.5 percent. Rates were similar in men and women. Significantly higher body mass index (BMI), weight, hip circumference, and fasting and postchallenge 2 hour blood glucose concentrations were associated with the presence of the Arg allele in women but not in men. The association with weight and hip measurements and with hyperglycemia was present only in women aged less than 55 years. In multivariate analysis, the mutation was associated with the BMI and sex in a model that also included age. The variation in fasting and 2 hour blood glucose levels were predicted by beta3-AR, gender, age and BMI. These results suggest that the presence of the mutation contributes to obesity and hyperglycemia in our female population.(AU)

Protein metabolism in skeletal muscle

Two different approaches towards the study of protein turnover in skeletal muscle were made. The first approach involved the injection of 75Se Selenomethionine into rats and the subsequent measurement of the whole body decay rate of the 75Se activity in a 4 pi liquid scintillation counter. By this means it was hoped that the whole body decay curve could be analysed into exponentials representative of 'fast' (visceral protein) and 'slow' (muscle protein) pools. This proved not to be feasible. The special difficulties resulting from the use of 75Se-labelled amino acids are discussed. As a second approach a search was made for a technique for labelling muscle proteins so that radioactivity decay rates could be used directly to calculate rates of synthesis and catabolism without the usual errors arising from isotope reutilisation. 75Se selenomethionine, 14C-6 arginine, 14C-Na2 CO3 and 14C-1 glutamate were investigated. 14C-Na2 CO3 proved to be suitable especially if the decay rates of separate and glutamate isolated from muscle proteins labelled with 14C Na2 CO3 are measured. The lack of reutilisation of label is discussed in terms of the metabolic activity of the carboxyl groups of these dicarboxylic amino acids. The effects of acute deprivation of calories and protein on synthesis and catabolism of muscle and liver protein was measured in rats, using the 14C-Na2 CO3 labelling method. The synthesis rates for muscle proteins, 0.25 and 0.097 days-1 for sarcoplasmic and myofibrillar proteins respectively are the fastest reported in the literature. The total protein synthesised and catabolised in muscle sarcoplasmic and myofibrillar fractions was calculated and compared with liver. The protein free diet caused a reduction in synthesis rates in liver and muscle protein with no change in the distribution pattern between the tissues. The starved rats showed a shift in the distribution pattern of synthesis towards liver and a concomitant shift towards muscle in catabolism. The results are discussed in terms of the mobility and therefore importance of muscle protein metabolism in the economy of the whole animal (AU)

Protein turnover in skeletal muscle. I. The measurement of rates of synthesis and catabolism of skeletal muscle protein using [14C]Na2CO3 to label proteins

The turnover of rat skeletal muscle protein was studied using [75Se]selenomethionine, [6-14C]arginine and [14C]Na2CO3 to label protein. In rats labelled with both [75Se]selonomethionine and [14C]Na2CO3 the 14C activity of mixed skeletal muscle protein fell rapidly with a half-life of 6.0 days for the specific activity and 10.5 days for the total activity. There was no loss of 75Se activity from muscle protein during the 12 days of the experiment. Following the injection of [6-14C]arginine both sarcoplasmic and myofibrillar proteins continued to incorporate label for 6 days after which time the label was lost fairly rapidly. Following injection of [14C]Na2CO3 muscle protein was maximally labelled by 6h, at which time specific activity of the free amino acids had fallen to a very low level. Aspartate and glutamate in particular had lost over 99 percent of their maximum activity by this time in comparison to arginine which was still highly labelled after 24h. 14C activity was lost more rapidly from aspartate and glutamate isolated from sarcoplasmic and myofibrillar protein than from other labelled amino acids. The half-lives of the two protein fractions were 3.9 and 7.2 days from the specific activity curves and 6.0 and 19.0 days from the total activity curves. The differences between the half lives of muscle proteins labelled with amino acids are discussed in terms of the effects of reutilization of the labelled amino acids used. It is postulated that aspartate and glutamate labelled by the injection [14C]CO3= are only reutilized to a very small extent and therefore afford the means by which the rates of protein synthesis and catabolism in skeletal muscle can be measured with reasonable accuracy (Summary)

Stimulation of insulin secretion in vitro by essential aminoacids

Leucine was the only essential aminoacid to stimulate insulin release from rabbit pancreas in vitri in the absence of extracellular glucose. In the presence of 1.5 mg glucose, per ml leucine, arginine, lysine and isoleucine were effective stimuli of insulin release (Summary)