No abstract

The pattern of GH secretion undergoes substantial changes in the aging rat, resulting in decreased daily secretion of GH. In this study, the pituitary responsiveness to GH-releasing factor (GRF) was examined in young (2- to 5-month old) and aging (14- to 18-month old) male rats. In vivo studies were performed under sodium pentobarbital anesthesia. After injection of 250 ng GRF/100 g BW, young rats experienced more GH secretion [peak level, 544.5 +/- 209.5 (+/- SEM) ng/ml] than did 18-month-old rats (89.3 +/- 13.7 ng/ml). To investigate the locus of this insensitivity to GRF, anterior pituitary cells from young and aging rats were dispersed and placed in primary culture. While basal GH secretion from the cultured pituitary cells was similar in the two groups (49.7 +/- 3.5 vs. 47.8 +/- 2.7 ng/ml X 4 h for the 2- and 18-month old rats, respectively), the GH-releasing ability of GRF was partially but significantly impaired in cells derived from both 14- and 18-month old rats; 100 nM GRF stimulated the release of 96.7 +/- 1.8 ng/ml X 4 h in the 18-month old rats as opposed to 115.0 +/- 6.0 (P less than 0.05) ng/ml X 4 h in the 2-month-old rats. Since GRF stimulates GH release through the activation of adenylate cyclase, intracellular cAMP levels were measured in the cultured pituitary cells. GRF stimulated 65% less intracellular cAMP accumulation in the 18-month-old rats. In 14-month-old rats, the ability of forskolin and (Bu)2 cAMP to release GH was impaired, while phorbol ester-elicited GH secretion was unchanged. In conclusion, the GH response to GRF is blunted in aging rats. While much of the insensitivity to GRF may be mediated by the increased somatostatin tone reported in aging rats, a diminished pituitary cAMP response to GRF may also be an important etiological factor in the hyposomatotropinemia of the aging male rat.

No abstract

The effect of age on glucose tolerance, as differentiated from the effects of obesity, work and leisure physical activity, family history of diabetes, and the use of drugs known to adversely affect glucose tolerance and/or insulin secretion, has been analyzed in 732 factory workers aged 22 to 73 years. Glucose tolerance, as evaluated by the plasma glucose response to 75 g of oral glucose deteriorated with age, associated with an increase in plasma insulin levels. However, the age-related decrease in glucose tolerance also correlated significantly with degree of obesity, leisure-time physical activity, and the use of potential diabetogenic drugs. Partial correlation coefficients were calculated to define the effect of age per se on glucose tolerance, controlling for the presence of these other age-related variables. When this was done, the degree of correlation between age and glucose tolerance was reduced, particularly in women, to where it became of marginal statistical significance. The effect of age on insulin response was affected to a greater degree by age-related variables, and was no longer statistically significant when these other factors were taken into consideration. These data suggest that the elevation in plasma glucose and insulin levels associated with age are to a certain extent due to age-related environmental factors, and the deterioration in glucose tolerance with age is relatively modest in magnitude in a generally healthy population.

A study was carried out to evaluate the acute effect of an intravenous injection of metformin on the fasting plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in 15 non-diabetic subjects. Metformin (1 g) was administered as a bolus in a peripheral vein and blood was sampled 2, 5, 10, 15 and 30 minutes after the drug injection. No significant change in fasting concentration of glucose nor in C-peptide, insulin, glucagon and growth hormone fasting levels was noticed. It is concluded that metformin does not possess an acute direct hypoglycaemic effect in non-diabetic subjects and does not acutely affect the basal activity of endocrine pancreas and pituitary gland in releasing insulin, glucagon and growth hormone.