Lactational Responses to Postruminal Administration of Proteins and Amino Acids

The objectives of this study were 1) to determine how cellular growth of skeletal muscle is altered by the repartitioning agent cimaterol and 2) to determine if cimaterol alters endocrine status in association with its repartitioning effects. Thirty Dorset wether lambs were randomly assigned to a pre-treatment baseline group or received 0 or 10 ppm cimaterol in a complete, mixed, high-concentrate diet for 7 or 12 wk. Weights of biceps femoris (BF), semimembranosus (SM) and semitendinosus (ST) muscles were 32.8, 27.1 and 31.5% greater, respectively, in treated lambs at 7 wk, and were 22 to 24% greater at 12 wk. Longissimus (LD) cross-sectional area was 26 and 32% greater at these treatment intervals. Percent type I fibers declined significantly over the course of the experiment in ST, SM and LD, and cimaterol caused a small but significant reduction in percent type I fibers in the ST at 7 and 12 wk. Muscles from lambs fed cimaterol contained 50 and 75% more fibers that exhibited negative staining for phosphorylase activity. Mean cross-sectional area of type I and type II fibers in the combined portions of the ST were 30.4 and 29.3% greater, respectively, in cimaterol-fed lambs after 12 wk, while type I and type II fiber areas in the longissimus were only 13 and 15% greater, respectively. Cimaterol-induced hypertrophy of the ST resulted in both protein and RNA content being 30 to 35% greater (P<.01) at 7 and 12 wk, while DNA concentration was 22% less (P<.O1) at 7 wk. DNA concentration returned to normal by 12 wk. These results indicate that cimaterol elicits a rapid increase in muscle RNA and protein accretion without concurrent incorporation of satellite cell nuclei. Plasma insulin and insulin-like growth factor-1 (IGF-1) concentrations were 55 and 34% lower, respectively, in cimaterol-fed lambs. Plasma somatotropin concentration and area under the curve were 2.3 times greater (P<.01) in lambs fed cimaterol for 6 wk, while plasma cortisol, prolactin and glucose concentration were unaffected at 6 or 12 wk. The significant changes in endocrine status may be important in the mechanism(s) of cimaterol in altering muscle accretion.

Cimaterol-induced muscle hypertrophy and altered endocrine status in lambs.

RECENT reports that epinephrine and glucagon, hormones which affect the generation of cyclic 3′,5′-AMP, also influence the release of pancreatic insulin1–5 have led us to examine the effect of this cyclic nucleotide on insulin secretion. In the present experiments the effects on insulin secretion of theophylline, a methyl xanthine derivative which inhibits cyclic nucleotide phosphodiesterase6 and increases the intracellular steady state level of cyclic 3′,5′-AMP, alone and in combination with epinephrine and alpha and beta adrenergic blocking agents, have been examined in the rat.

Stimulation of Insulin Secretion by Theophylline

This review summarizes evidence showing inhibition of insulin release by epinephrine and norepinephrine. The receptor theory for catecholamine action is discussed and the inhibition shown to be mediated by α-adrenergic receptor stimulation; β-adrenergic receptors are also described which stimulate insulin release, indicating a unique dual receptor system in the pancreatic islet. The possible physiologic importance of these findings is suggested in a discussion of the carbohydrate intolerance found in patients with pheochromocytoma and during severe hypothermia in children. A possible relation of the inhibition of insulin release and the increased fatty acid mobilization caused by catecholamines to exacerbations of the diabetic syndrome is examined. It is postulated that the catecholamine release which is stimulated by volume depletion, infection, or stress may be an important "reversible" factor in some patients with diabetic ketoacidosis.

Sympathetic Regulation of Insulin Secretion: Its Relation to Diabetes Mellitus

Relation of Hormonal Variations to Nutritional Studies and Metabolism of Ruminants

Epinephrine infusions (0.5–1.0 μg/kg/min) inhibited the insulin secretory response to the short-chain fatty acids propionate (0.5 mmole/kg) and butyrate (0.5 mmole/kg) and intravenous arginine (12.5 g). This inhibitory effect of epinephrine was blocked by alpha adrenergic receptor blockade (i.e., phentolamine) but not by beta adrenergic receptor blockade (i.e., propranolol). Epinephrine also completely abolished the plasma growth hormone response to arginine infusions. This effect was not altered by alpha adrenergic receptor blockade sufficient to reverse the inhibitory effect of epinephrine on insulin secretion. A significant increase (i.e., 5- to 10-fold) in plasma growth hormone was consistently noted 30–60 min after stopping the infusion of epinephrine. Short-chain fatty acids were demonstrated to stimulate insulin secretion in the newborn lamb, which at birth is monogastric and does not have a functioning forestomach. This result indicates that the capacity of the ruminant to respond to shortchain fa...

Further studies on the regulation of insulin and growth hormone secretion in the sheep.

Plasma levels of growth hormone (GH), measured by radioimmunoassay, increased slightly following the intravenous injection of insulin sufficient to provoke severe hypoglycemia. No change in the basal plasma GH level was observed when hyperglycemia was produced by either oral or intravenous glucose. When the blood glucose level fell very rapidly, as seen after cessation of an iv infusion of glucose, plasma GH increased 3-fold. Plasma GH increased from basal levels of 5.8 ±0.8 to a maximum of 12.1 ±1.8 μg/ml after 2 days of starvation and then decreased toward control values with further fasting. Stress and exercise provoked significant increases in plasma GH, but the injection of catecholamines in amounts sufficient to produce hyperglycemia and FFA mobilization had no effect on plasma GH. It was concluded that the changes in plasma GH are sluggish in the pig compared to those seen in the normal-weight human. Injection of porcine GH (0.1-1.0 mg/kg) into the pig resulted in an initial decrease in plasma free...

Plasma Growth Hormone and Insulin Levels in the Pig

SummaryThe effect of intravenous infusion of epinephrine was studied in pigs. FFA increased 8–10-fold within an hour, and this high level was maintained throughout a 6-hour infusion period. During the infusion of epinephrine, the mean plasma insulin concentration remained below 2 μU/ml, despite marked severe hyperglycemia. Within 30 minutes after the withdrawal of epinephrine there was a 4–6-fold increase of plasma insulin. This was accompanied by a gradual decrease of glucose and FFA. By the time blood sugar and FFA fell to preinfusion levels insulin also returned to normal. It appears that epinephrine blocks insulin release normally induced by high blood sugar levels.

Lipolytic activity and inhibition of insulin release by epinephrine in the pig.

Extracts of bovine stalk-median eminence fragments (SME) equivalent to 3–5 glands were infused into the carotid artery of young sheep. Plasma GH increased from 4.8 at zero time to 17.7 mμg/ml 30 min after infusion had begun. Infusion of saline or cerebrum extracts had no effect on plasma GH. SME extracts also caused an elevation of plasma glucose and insulin which preceded the rise in GH. Evidence is presented which indicates that the rise in plasma GH levels is not a response to insulin but is a direct effect of a releasing factor in the SME extracts. (Endocrinology 80: 205, 1967)

L. J. Machlin

Papers

Further studies on the regulation of insulin and growth hormone secretion in the sheep.

Plasma Growth Hormone and Insulin Levels in the Pig

Lipolytic activity and inhibition of insulin release by epinephrine in the pig.

Stimulation of growth hormone secretion by median eminence extracts in the sheep.